CAR-T Cells – Main Steps for Obtaining a Proper “Live Drug” Adoptive Therapy

Main Article Content

Monica Neagu
Carolina Constantin

Abstract

Chimaeric antigen receptor (CAR) T lymphocytes (CAR-T) discovered in 1992 have been in the recent years in the spotlight of both researchers and clinicians. Immune therapy with engineered CAR-T cells has been approved by the FDA since 2017 for pediatric and young adult acute lymphoblastic leukemia. Since then, around ten therapies were approved for hematological cancers. In contrast to the other immune therapies CAR-T cell therapy is considered a “living drug” with the capacity of self-replicating. Having this particular characteristic, the manufacturing process has in general several steps that should be followed in the process of obtaining specific CAR-T cells. There are mandatory steps for obtaining a CAR-T cell culture: Leukapheresis, activation, gene delivery, expansion, and cryopreservation. All these seminal stages have various sub-stages that can differ from one procedure to other as detailed in the paper. Leukapheresis harvests peripheral blood mononuclear cells, followed by an enrichment of a certain cellular population or a depletion phase to remove contaminants as red blood cells and platelets. T cell population that is obtained needs to be activated using activating antibodies (Abs), magnetic beads coated with activating Abs or artificial antigen-presenting cells. After activation, T cells are subjected to genetic engineering that can be done using electroporation of naked DNA, plasmids, or viral vectors to insert the specific CAR. The last phases of CAR-T cell manufacturing are the expansion of these specific cells and, if not freshly inoculated to the patients, the final step is cryopreservation. The main drawback of CAR-T cell therapy is its high cost; therefore, new automated platforms would decrease their cost. The described stages are still variable within CAR-T manufacturing. Therefore, the future of this immune therapy will have to tackle standardization and automated technology, directions that will increase healthcare system availability.

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How to Cite
1.
Neagu M, Constantin C. CAR-T Cells – Main Steps for Obtaining a Proper “Live Drug” Adoptive Therapy. SEE J Immunol [Internet]. 2024 Jan. 23 [cited 2024 Jun. 16];7:13-20. Available from: https://seejim.eu/index.php/seejim/article/view/6063
Section
Clinical Immunology
Author Biography

Monica Neagu, Department of Immunology, Victor Babes National Institute of Pathology, Bucharest, Romania; Department of Pathology, Colentina Clinical Hospital, Bucharest, Romania; Doctoral School, University of Bucharest, Bucharest, Romania

Monica Neagu, Head of Immunobiology Laboratory,“Victor Babes†National Institute and Habilitated Professor of Immunology at the University of Bucharest, Faculty of Biology. PhD thesis (1996) focused on immune parameters that favor chronic staphylococcal infections. During PhD she specialized in autoimmunity at Novartis Ltd, Basel, Switzerland. Since then, she has conducted over 35 national and international research grants focusing on immune biomarkers in various human pathologies. She is co-inventor of 6 patents focusing on photodynamic therapy which have been awarded with First Prizes and Gold Medals at international invention fairs.

She has conducted NATO SfP 982838/2007 Development of a novel immunoassay for the very early detection of Biothreatening bacterial infections. She has conducted various bilateral co operations, participated in FP7, EU Structural Funds Projects and international clinical studies. She was part of the management team for COST (Action D39) member of ETPN, member of CAT - EMEA (2010-2013). She is international project evaluator and member of Editorial Boards in international journals, guest leading editor for international books and special issues. She has a portfolio of over 100 published papers.

List of Publications

Books:

  • Dictionary of Biochemistry and Molecular Biology, Elena Moldovan, Monica Neagu, Laurentiu M. Popescu, Medical Publishing House, 2001
  • Methods in humoral and cellular immunology, Dorel L. Radu, Crina Stavaru, Iuliana Caras, Gina Manda, Monica Neagu, Eugen Radu, Cornel Ursaciuc, Laurentiu Mircea Popescu, Ed. University “Carol Davilaâ€, Bucharest, 2006, ISBN: 973-708-084-X
  • Chapter Advances in Pancreatic Cancer Detection, Cristiana Pistol Tanase, Monica Neagu, Radu Albulescu, Mihail Eugen Hinescu in Advances in Clinical Chemistry, 51, Pages 145-180,  2010 ISBN 13: 978-0-12-380981-0
  • Chapter 9 Application of electron accelerators in conjunction with microwave sources for medical studies, Diana Martin, Gabriela Craciun, Irina Margaritescu, Monica Neagu, Elena Manaila, Daniel Ighigeanu, Laurentiu Tudor and Nicusor Iacob, in „Ultrasound and Microwave: Recent Advances in Organic Chemistry, 2011: ISBN: 978-81-7895-532-2, Editors: Jean Pierre Bazureau and Micheline Draye
  • Dermato-oncology, Set of 2 Volumes,  Vol. 1, Vol. 2, Authors (in alphabetical order): Robert Ancuceanu, Corina Baican, Daniel Boda, Daciana BrăniÅŸteanu, Daniel BrăniÅŸteanu, Constantin Căruntu, Constantin Ciuce, Carolina Constantin, Rodica Cosgarea, Adriana Diaconeasa, Laszo Fekete, Julia Edit Fekete, Ana-Maria Forsea, Dan Forsea, Nicolae Fotin, Victor Georgescu, Daniela GuÅ£u, Mihai Ioana, Gabriel IanoÅŸi, Simona IanoÅŸi, Rodica Ion, Mihaela Leventer, Francisc Mixich, Roxana Mustaţă, Monica Neagu, DragoÅŸ Pieptu, Florian Popa, Cătălin Popescu, Raluca Popescu, Sanda Popescu, Caius Solovan, Simona Åženilă, Florica Stăniceanu, LaurenÅ£iu Vlădău, Cristiana Tănase, DragoÅŸ Teodorescu-Brânzeu, Sabina Zurac, Editura Universitară „Carol Davila†BucureÅŸti 2011-2013, ISBN: 978-973-708-542-9
  • Chapter 5 Immune-therapy in cutaneous melanoma – efficacy immune markers Monica Neagu, Carolina Constantin in "Advancements in Tumor Immunotherapy and Cancer Vaccines ", pages 83-106, InTech, February 2012, ISBN 978-953-307-998-1
  • Chapter 5 The immune system - a hidden treasure for biomarker discovery in cutaneous melanoma, Monica Neagu, In Gregory S. Makowski, editor: Advances in Clinical Chemistry, Burlington: Academic Press vol 58, 2012 pp. 89-140 ISBN: 978-0-12-394383-5
  • Fundamental Immunology Compedium, Ursaciuc C, Neagu M, Manda G, Romanian Medical Life Ed, 2012, ISBN 978-973-160-057-4
  • Immunogenomics, Immunotranscriptomics compendium, Ursaciuc C, Neagu M, Constantin C, Dobre M, Huica R, Romanian Medical Life Ed, 2013, ISBN 978-973-160-080-2
  • Proteomics from research to clinic, Tanase C, Neagu M, Albulescu R, Constantinescu S.N, Constantin C, Manole E, Popescu ID, Codrici E, Mihai S, Albulescu L, Romanian Medical Life Ed, 2013, ISBN 978-973-160-075-8
  • Chapter 9 New Insights in Cutaneous Melanoma Immune-Therapy — Tackling Immune-Suppression and Specific Anti-Tumoral Response, Monica Neagu and Carolina Constantin in “Melanomaâ€, Book edited by: Prof. Mandi Murph, InTech, published on-line 2015, p 225-246, ISBN 978-953-51-2036-0.
  • Chapter 8 Stem Cell standing at the Immune Processes Cross Roads -Tumorigenesis versus Regeneration, Monica Neagu and Carolina Constantin in “Stem Cells between Regeneration and Tumorigenesisâ€, Editors Cristiana Tanase and Monica Neagu, Bentham Pbl. House, 2015, Provisional number 27-8-2013-Ebk1//EOI-205.

 

Research papers – A1 publications

1. Follow-up cell mediated immune functions in “professional†blood donors, A. Olinescu, Sanda Hristescu, Gina Manda, Monica Neagu, T. Georgescu, Arch. Roum. Path. Exp. Microbiol., T47 (3-4): 283-288, 1988.

2. Inhibitory effect of interleukin-1 on the in vitro PHA-stimulated lymphocytes on some blood donors, A. Olinescu, Sanda Hristescu, Gina Manda, Monica Neagu, Fanica Agache, Arch. Roum. Path. Exp. Microbiol., T47 (3-4): 289-297, 1988.

3. A nonspecific immunostimulant effect with Cantastim on the cellular and humoral immune responses in mice evaluated by in vivo and in vitro tests, A. Olinescu, Sanda Hristescu, Aurora Salageanu, Gina Manda, Monica Neagu, Rev Ig Bacteriol Virusol Parazitol Epidemiol Pneumoftiziol, 34(4):325-336, 1989.

4. In vivo and in vitro effect of Cantastim, an immunomodulatory agent extracted from a highly pathogenic Pseudomonas aeruginosa strain, A. Olinescu, Sanda Hristescu, Aurora Salageanu, Gina Manda, Monica Neagu, Neoplasma, 38 (1): 119-128, 1991. ISSN 0028-2685

5. The in vitro action of a succussed substance on the proliferative response of human lymphocytes stimulated with phytohemagglutinin, Chirila M, Hristescu S, Manda G, Neagu M, Olinescu A. Rom J Intern Med, 30(1):63-67, 1992.               

6. Action of some proteic and sugar components of Symphytum officinale upon normal and neoplastic cells, A. Olinescu, Gina Manda, Monica Neagu, Sanda Hristescu, C. Dasanu, Roum. Arch. Microbiol. Immunol., 52 (2): 73-79, 1993.

7. Selective immunosuppression by administration of MHC class II - binding peptides. II Preventive inhibition of primary and secondary in vivo antibody response, J-Ch. Guery, Monica Neagu, Gemma Rodriguez-Tarduchy, L. Adorini, J. Exp. Med., 177 : 128 - 136, 1993. ISSN:  0022-1007.

8. Immune intervention in autoimmune diseases-MHC blockade, Monica Neagu, Roum. Arch. Microbiol. Immunol., 52 : 165-169, 1993.

9. The influence of some serine-proteases inhibitors on respiratory burst of human normal peripheral polymorphonuclear granulocytes in vitro  stimulated with opsonized zymosan, Monica Neagu, Gina Manda, Maria Chirila, Elena Mazilu, A. C. Bancu, L. M. Popescu, Rev. Roum. Biochim., 32 (3-4): 131-136, 1995.

10. The effect of thiol compounds on the respiratory burst in polymorphonuclear granulocytes, Marina Tamara Nechifor, Marinela Bostan, Monica Neagu, Gina Manda, I. F. Dumitru, Roum.Biotechnol.Lett., 1(2): 98-105, 1996.

11. Functional interferences between CR3 and the receptors for N-formylated peptides regarding the respiratory burst of PMNs in vitro  stimulated with zymosan particles and fmlp, Gina Manda, Monica Neagu, Alexandra Livescu, Marinela Bostan, Maria Chirila, Elena Mazilu, A.C. Bancu, L.M. Popescu, Rev. Roum. Biochim., 33 (3-4): 191-199, 1996

12. Interferences at the respiratory burst level between the signals delivered in vitro to human peripheral neutrophils via fMLP, complement and Fc receptors, Marinela Bostan, Alexandra Livescu, Monica Neagu, Gina Manda, Maria Chirila, Elena Mazalu, A. C. Bancu , L.M. Popescu, Immuneregulation in Health and Disease, Experimental and Clinical Aspects, edited by M.L.Lukic, M. Colic, Marija Mostarica-Stojkovic and K. Cuperlovic, Academic Press, Section 4: Host reactivity to graft, tumor and infection, Chapter 41, p. 431-438, 1997.

13. The immune response induced by a split influenza vaccine. Part I. Studies on cellular immunity, V. Alexandrescu,  Gina Manda, Monica Neagu,  D. Ciotaru, E. Ionita, Rom. Arch. Microbiol. Immunol., 56(3-4): 155-164, 1997.

14. Peripheral leukocytes activation in aortic aneurysmal disease, Tanaseanu C, Neagu M, Popescu M, Manda G, Cojocaru M., Rom J Intern Med., 36(3-4):167-174, 1998.

15. Flow Cytometry Measurements of Intracellular pH in Different Stages of Cell Evolution, Laura Olariu, Brandusa Dumitriu, Gina Manda, Monica Neagu, Journal of Medicine and Biochemistry, 4(4), 1998.

16. Changes in albumin fraction after in vitro UVA irradiation of human plasma, Marina Nechifor, Monica Neagu, Gina Manda, Marinela Gaghes, Journal of Medicine and Biochemistry, 3(3), 283-287,1999.

17. Total depletion of extracellular calcium ions favors superoxide anion release by human normal peripheral granulocytes, Gina Manda, Monica Neagu, Alexandra Livescu, Marinela Bostan, A. C. Bancu, Journal of Medicine and Biochemistry, 1999, vol.3, nr.4, 333-341.

18.The In vitro Action of a Succussed Substance on the Proliferative Response of Human Lymphocytes Stimulated with Phytohemagglutinin, M Chirila, S Hristecu, G Manda, M Neagu, A Olinescu BIOMEDICAL THERAPY, 1999, Volume 17, Pages 73-75

19. Mannose-coated liposomes as adjuvant for influenza virus vaccine: stimulation of respiratory burst of mouse peritoneal macrophages, Carmen Popescu, Viorel Alexandrescu, Dan Ivanov, Gina Manda, Monica Neagu, Journal of Medicine and Biochemistry, 4(1), 51-55, 2000.

20. Efects of synovial fluid on the respiratory burst of granulocytes in rheumatoid arthritis, Marinela Bostan,Lorelai Brasoveanu, Alexandra Livescu, Gina Manda, Monica Neagu, Dana Iordachescu, Journal of Cellular and Molecular Medicine, 5(2): 188-194, 2001

21. Involvement of complement and Fc receptors in the respiratory burst of neutrophils, Alexandra Livescu, Carolina Constantin, Gina Manda, Monica Neagu, Scand. J. Immunol., 54 (Suppl.1): B9/1002: 84, 2001. Online ISSN: 1365-3083

22. Cellular parametres prognosticate acute cardiovascular disease outcome, Monica Neagu, Gina Manda, Alexandra Livescu, Carolina Constantin, Scand. J. Immunol., 54 (Suppl.1): A5/1263: 96, 2001. Online ISSN: 1365-3083

23. The relation between experimental tumor and chronic inflammation in malignant process evolution, Carolina Constantin, Alexandra Livescu, Gina Manda, Rodica Dumitrescu, Monica Neagu, Scand. J. Immunol., 54 (Suppl.1): K1/1361: 75, 2001. Online ISSN: 1365-3083

24. In vitro immunomodulatory action of low doses of methotrexate in rheumatic diseases, Gina Manda, Monica Neagu, Carolina Constantin, Alexandra Livescu, Scand. J. Immunol., 54 (Suppl.1): A7/1361: 116, 2001. Online ISSN: 1365-3083

25. Alcohol and antioxidant enzymes in rat liver, Marina Nechifor, Gheorghe Stoian, Monica Neagu, Gina Manda, Diana Dinu, Ovidius University Annals of Biology-Ecology, 5: 43-46, 2001.

26. The influence of experimental alcohol ingestion on the functionality of rat splenocytes, Monica Neagu, Gina Manda, Carolina Constantin, Alexandra Livescu, Diana Dinu Gheorghe Stoian, Marina Nechifor, Ovidius University Annals of Biology-Ecology, 5: 47-50, 2001.

27. The in vitro effect of low molecular weight heparin on peripheral blood leukocytes from patients with cardiovascular diseases, Monica Neagu, Gina Manda, Carolina Constantin, Cristina Tanaseanu, D. P. Mikhailidis, International Angiology, 20 (2), 164-173, 2001. ISSN: 1061-1711

28. Chronic ethanol consumption affects the activity of antioxidant enzymes in rat liver, Marina Nechifor, Diana Dinu, I.F. Dumitru, N. Balta, Monica Neagu, Gina Manda, Gh. Stoian, Romanian Journal of Physiology (Physiological Sciences), 38 (1-4):127-134, 2001.

29. Alcohol dehydrogenase in the blood serum of rats with chronic alcoholism, Diana Dinu, Gh. Stoian, Marina Tamara Nechifor, Monica Neagu, Gina Manda, N. Balta, M. Ioan, I.F. Dumitru, Romanian Journal of Physiology, (Physiological Sciences), 38 (1-4):135-140, 2001.

30. The involvement of reactive oxygen species in the development of unstable angina, Monica Neagu, Gina Manda, Alexandra Livescu, Carolina Constantin, Marina T. Nechifor, Isabela Tamsula, Monica Popescu, Cristina Tanaseanu, Roumanian Biotechnological Letters, 8(1): 1083-1092, 2003

31. Receptor and dose-dependent effects exerted in vitro by methotrexate on human immune cells, Gina Manda, Monica Neagu, Alexandra Livescu, Carolina Constantin, Catalin Codreanu, Marina T. Nechifor, Roumanian Biotechnological Letters, 8(1): 1139-1147, 2003

32. Imbalance between peripheral B lymphocytes and NK cells in rheumatoid arthritis, G. Manda, M. Neagu, A. Livescu, C. Constantin, C. Codreanu, A. Radulescu, Journal of Cellular and Molecular Medicine, 7(1): 79-88, 2003

33. Plasma membrane potential interfers with the respiratory burst of peripheral granulocytes, Alexandra Livescu, Gina Manda, Carolina Constantin, Monica Neagu, Dana Iordachescu, Journal of Cellular and Molecular Medicine, 7(1): 73-78, 2003

34. Functional parameters of peripheral neutrophils isolated from unstable angina patients, Livescu A., Neagu M., Constantin C., Manda G., Gaghes M., Tanaseanu C, Immunology  Letters, Special Issue, Vol. 87, No. 1-3: 44-45, 2003;

35. Evaluation of peripheral lymphocytes subpopulation in cardiovascular diseases, Neagu M., Manda G., Gaghes M., Livescu A., Constantin C., Tamsula I., Popescu M, Tanaseanu C, Immunology  Letters, Special Issue,Vol. 87, No. 1-3: 95, 2003;

36. In vivo inhibition of dihydroorotate dehydrogenase with leflunomide modulates the functions of peripheral granulocytes in rheumatoid arthritis, Manda G., Neagu M., Livescu A., Constantin C., Codreanu C., Immunology  Letters, Special Issue, Vol.87, No 1-3 : 243, 2003

37. Platelet-Activating factor acetylhydrolase activity in patients with chronic stable angina (preliminary results), Tanaseanu C., Moldoveanu E, Kosaka T., Neagu M., Tanaseanu S., Popescu M., Tamsulea I., Urban A., Romanian Journal of Internal Medicine, vol 41(2):145-152, 2003

38. In vitro investigation of immunotoxicity of chlorpyrifos. Note II: effects registered upon human peripheral blood lymphocytes proliferation asupra, Daniela Luiza Baconi, Gina Manda, Dan Bălălău, Monica Neagu, Mihaela Ilie, Farmacia (ISSN 0014-8237), LI (6),: 87-91, 2003.

39. Experimental model of antitumoral photodynamic therapy with phtalocyanines – pathological evaluation

Tănase Cristiana, Monica Neagu, G. Savi, Rodica Carstoiu, Rodica Mariana Ion, Eleonora Codorean, Elena Raducan, Daniela Popescu, Gina Manda, Carmen Ardeleanu, II Intercontinental Congress of Pathology, Proceeding, Iguassu Falls (Brazil) June 9-13, 2004, Editors Fernando Soares, Jose Vassallo, Luiz Fernando Bleggi Torres, Medimond International Proceedings, Medimond - Monduzzi Editore, Italia, 121-125, 2004, ISBN:978-88-7587-050-8.

40. Apoptosis in pituitary adenomas; comparative study by flow cytometry and in situ end-labeling technique, Tănase Cristiana, E. Codorean, C. Ardeleanu, G. Butur, G. Manda, M.Neagu, E. Radu, D.I. Popescu, E. Raducan, M.L. Cruceru , M.A. Niculescu, V. Ciubotaru, I. Ogrezean, II Intercontinental Congress of Pathology, Proceeding, Iguassu Falls (Brazil) June 9-13, 2004, Editors Fernando Soares, Jose Vassallo, Luiz Fernando Bleggi Torres, Medimond International Proceedings, Medimond - Monduzzi Editore, Italia, 117-120, 2004, ISBN:978-88-7587-050-8

41. Proliferation and apoptosis in relation to treatment response in pituitary adenomas, C Tanase, E Codorean, G Manda, M Neagu, DI Popescu, E Raducan, ML Cruceru, G Butur, M Neagu, C Ardeleanu, Exp Clin Endocrinol Diabetes 2004; 112

42.The significance of human platelet activating factor – acetylhydrolase in patients with chronic stable angina, Cristina Tanaseanu, Elena Moldoveanu, Tetsuya Kosaka, Stefanita Tanaseanu, Monica Neagu, Laurentiu M Popescu, Eur J Intern Med., Aug;15(5):291-297, 2004 ISSN: 0953-6205

43. Unstable angina is accompanied by immune cells dysfunction, Monica Neagu, Gina Manda, Carolina Constantin, Marina Nechifor, Cristina Tanaseanu, Romanian Archives of Microbiology and Immunology, 63 (3-4): 169-180, 2004.

44. The effect of laser activation of 5,10,15,20-tetra-sulphophenyl-porphyrin loaded in K562 cells and human normal mononuclear cells, Carolina Constantin, Monica Neagu, Gina Manda,  Rodica-Mariana Ion and Dana Iordachescu, Romanian Archives of Microbiology and Immunology, 63(3-4):165-179, 2004.

45. Patients with primary antiphospholipid syndrome and coronary microvascular dysfynction – a distinct clinical set, Cristina Tanaseanu, Elena Moldoveanu, St. Tanaseanu, Monica Popescu, Alina Dumitrascu, Isabela Tamsula, Antoaneta Urban, Viorica Grecu, Monica Neagu, Gabriela Manea, Daciana Marta, Rom. J Intern Med, 42(3):545-556, 2004.

46.The effects of organophosphate chlorpyrifos on immune function in rats, Daniela Baconi, Gina Manda, Monica Neagu, Dan Bălălău, Mihaela Ilie, Maria Barca, Timisoara Medical Journal (ISSN 1583-5251), 55, suppl. 5: 152 – 155, 2005

47.Patterns of peripheral cellular immune disorders in severe rheumatoid arthritis Gina Manda, Monica Neagu, Carolina Constantin, Alina Radulescu, Catalin Codreanu, Romanian Archives of Microbiology and Immunology, 64: 17-26, 2005

48.The immunologically active site of prothymosin alpha is located at the carboxy-terminus of the polypeptide.Evaluation of its in vitro effects in cancer patients, Margarita Skopeliti, Ioannis F. Voutsas, Persefoni Klimentzou, Marinos L. Tsiatas, Alexander Beck, Aristotelis Bamias, Maria Moraki, Evangelia Livaniou, Monica Neagu, Wolfgang Voelter, Ourania E. Tsitsilonis, Cancer Immunol Immunother  Oct; 55(10):1247-1257, 2006, DOI 10.1007/s00262-005-0108-4 ISSN 0340-7004

49. Markeri moleculari implicati în etiopatogenia, diagnosticul si prognosticul insuficientei cronice venoase si ale ulcerului cronic de gamba, Daniel Boda, Adriana Diaconeasa, Monica Neagu, Gina Manda, Carolina Constantin, Horatiu Rus, Dermato.ro Nr. 14 decembrie 2006 16-19, ISSN 1584-7608

50.Biochemical changes in rat testis induced in vitro by reactive oxygen species.Nechifor MT, Constantin C, Manda G, Neagu M, Dinu D.Roum Arch Microbiol Immunol. 2006 Jul-Dec;65(3-4):135-40.

51.Alzheimer’s disease delay: link to good physical function? László Csiba, Szabolcs Farkas, Peter F Ehrlich, Monica Neagu, Carolina Constantin, Cristiana Tanase, Stefan Kiechl, Philipp Werner, Michael Knoflach, Martin Furtner, Johann Willeit, Georg Schett, Expert Review of Neurotherapeutics, 2006, Volume 6, Issue 6, Pages 809-810

52. Synthetic porphyrins in experimental photodynamic therapy induce different antitumoral effect, Monica Neagu, Gina Manda, Carolina Constantin, Eugen Radu and Rodica-Mariana Ion, Journal of Porphyrins and Phthalocyanins, 2007 Jan;11 (1): 58-65 ISSN: 1088-4246

53. Laser effect in photodynamic therapy of tumors, Rodica-Mariana Ion, Dragos-Viorel Brezoi, Monica Neagu, Gina Manda, Carolina Constantin Proc. SPIE Vol. 6606, 66061G (Apr. 25, 2007) 253-261, doi:10.1117/12.730203

54. Mechanisms in photodynamic therapy: photosensitizers and cellular localization on K562 cells Rodica-Mariana Ion, Monica Neagu, Gina Manda, Carolina Constantin, Mihaela Calin SPIE - The International Society for Optical Engineering.13 July 2007 Vol: 6632, DOI: 10.1117/12.727968

55.Immunotoxic effects of some organophosphate pesticides in rats, D Baconi, D Balalau, G Manda, M Neagu, M Barca, AM Ciobanu,Toxicology Letters 172, S206, 2007.

56. Cell Investigations Simultaneous with Exposure to 2.45 GHz Microwaves, D. Martin, S. Cinca, I. Margaritescu, M. Neagu, C. Matei, N. Iacob, D. Ighigeanu, G.Craciun, E. Manaila, D. Chirita, M. Moisescu, Journal of Microwave Power and Electromagnetic Energy 2008, vol 42 (4), pp. 751-754 ISSN: 0832-7832

57. Combined Microwave and Electron Beam Exposure Facilities for Medical Studies and Applications, D. Martin, S. Cinca, I. Margaritescu, M. Neagu, N. Iacob, D. Ighigeanu, C. Matei, G. Craciun, E. Manaila, D. Chirita, M. Moisescu, Journal of Microwave Power and Electromagnetic Energy 2008, vol 42 (4), 771-774 ISSN: 0832-7832

58.Assessment of soluble angiogenic markers in pancreatic cancer, Cristiana Pistol-Tanase‌, Elena Raducan‌, Simona Olimpia Dima‌, Lucian Albulescu‌, Ionita Alina‌, Poroschianu Marius‌, Linda Maria Cruceru‌, Eleonora Codorean‌, Teodora Monica Neagu‌ & Irinel Popescu‌Biomarkers in Medicine, Vol. 2, No. 5, Pages 447-455, 2008.

59.Preliminary study on the immunologic background of good clinical outcome in rheumatoid arthritis patients after one month therapy with leflunomide.Manda G, Neagu M, Constantin C, Neagoe I, Codreanu C. Rheumatol Int. 2009 Jun;29(8):937-46.

60. New Bicyclo[2.2.1]heptane Nucleoside Analogues as Antitumor Agents, C. Tanase, F.G. Cocu, M.T. Caproiu, Monica Neagu, Gina Manda, Rev. Chim. (Bucuresti), 60(2), 2009, 147-151.

61. Biomarkers of metastatic melanoma, Neagu Monica, Constantin Carolina, Manda Gina, Margaritescu Irina, Biomarkers In Medicine, Volume 3, Number 1, February 2009 , pp. 71-89(19)

62. Reactive Oxygen Species, Cancer and Anti-Cancer Therapies, Gina Manda, Marina Tamara Nechifor and Teodora-Monica Neagu, Current Chemical Biology, Pp. 22-46, Volume 3, Number 1, January 2009

63. Interferente neuro-imune la nivel de opioide, Gina Manda, Monica Neagu, Medicina moderna. Revista Colegiului Medicilor din Bucuresti, vol XV, nr.9, p.493.

64. Research Highlights, Monica Neagu, Carolina Constantin, Cristiana Tanase, Radu Albulescu, Biomarkers In Medicine, Vol. 3(4), 343 - 345, 2009.

65.Toxicological studies with cavitands organic structures in human immune cells experimental models, Constantin C., Neagu M., Manda G., Stavaru C., Radu D. L. and Ion R.-M. Proceedings of the 2nd European Congress of Immunology, Monduzzi Editore International Proceedings Division, pp 415 – 418, 2009.

66.SELDI-ToF-MS for prothymosin-alpha detection as bacterial infection apoptosis marker - NATO SfP Project, Neagu M., Constantin C., Manda G., Popescu D., Ungureanu V., Tatu D., Pana M., Radu D.L., Bulman A., Vorgias K., Tsitsilonis O., Voelter W. Proceedings of the 2nd European Congress of Immunology, Monduzzi Editore International Proceedings Division, pp 419 – 422,  2009.

67.Biomarkers in the diagnosis and early detection of pancreatic cancer, Cristiana Pistol Tanase‌, Monica Neagu‌, Radu Albulescu‌, Eleonora Codorean‌ & Simona Olimpia Dima‌,Expert Opinion on Medical Diagnostics, Vol. 3, No. 5, Pages 533-546, 2009

68.Key signaling molecules in pituitary tumors, Cristiana Pistol Tanase‌, Monica Neagu‌, Radu Albulescu‌, Expert Review of Molecular Diagnostics, 9(8), 859-877, 2009

69. Serum markers in skin melanoma – preliminary study, Georgiana Dumitrascu, Carolina Constantin, Gina Manda, Sanda Hristescu, Irina Margaritescu, D. Chirita, Monica Neagu, Roum Arch Microbiol Immunol, vol 69, pages 125-135, November 2009

70. New Photosensitizers Versus Aminolevulinic Acid (ALA) in Experimental Photodynamic Therapy of Actinic Keratosis – A Case Report, Daniel Boda, Monica Neagu, Carolina Constantin, Adriana Diaconeasa, Simona Ianosi, Rodica-Mariana Ion, Analele Stiintifice ale Universitatii Alexandru Ioan Cuza Din Iasi (Serie Noua)-Genetica si Biologie Moleculara, Tom X, Fascicola 3, pagina 61-69, 2009.

71.Fullerene-porphyrin nanostructures in photodynamic therapy, Carolina Constantin, Monica Neagu, Rodica-Mariana Ion, Mihaela Gherghiceanu, Crina Stavaru, Nanomedicine, 5(2), February 2010 Pages 307-317

72. Antitumoral Effect of Calixarenes on Experimental Photodynamic Therapy with K562 Tumor Cell Line, Monica Neagu, Rodica - Mariana Ion, Gina Manda, Carolina Constantin, Eugen Radu, Zoia Cristu, Romanian Journal of Biochemistry, issue 47(1), 2010, Pages 17-35

73.Microwave synthesis, basic spectral and biological evaluation of some copper (II) mesoporphyrinic complexes.Boscencu R, Ilie M, Socoteanu R, Oliveira AS, Constantin C, Neagu M, Manda G, Ferreira LF. Molecules. 2010 May 25;15(5):3731-43.

74.Photodynamic Therapy on B16 Cells with Tetrasulphonated Porphyrin and Different Light Sources, Simona-Florentina Pop, Rodica-Mariana Ion, Monica Neagu and Carolina Constantin, Journal of Materials Science and Engineering, 4 (3), March 2010 (Serial Number 28), 10-16.

75.Porphyrin (TPP)–Polyvinylpyrrolidone (PVP)–Fullerene (C60) Triad as Novel Sensitizer in Photodynamic Therapy Rodica Mariana Ion, Radu Claudiu Fierascu, Monica Neagu, Carolina Constantin, Crina Stavaru, Science of Advanced Materials, Vol. 2, 223–229, 2010

76.Biomarkers Discovery In Cancer – up-dates In methodology, Cristina Tacu, Monica Neagu, Carolina Constantin, Maria Sajin, Roum Arch Microbiol Immunol, vol 69(1), 2010, 48-55

77.Immune-related biomarkers for diagnosis/prognosis and therapy monitoring of skin melanoma, Monica Neagu, Carolina Constantin, Cristiana Tanase, Expert Review of Molecular Diagnostics, 10(7), 2010, 897-921.

78.Statistical correlations between peripheral blood lymphocyte subpopulations and tumour inflammatory infiltrate in stage I of skin melanoma Mariana Costache, Monica Neagu, Angela Petrescu, Carolina Constantin, Gina Manda, Camelia Vrabie, Mariana Waller, C.S. Petrescu, Olga Simionescu, Romanian Journal of Morphology and Embryology vol. 51 no. 4, 2010, 693-699.

79.Nano-engineered materials based on fullerenes: synthesis and biomedical applications, Fierascu, RC Dumitriu, I, Ion RM, Neagu, M , Constantin, C Stavaru, C, Advanced Topics In Optoelectronics, Microelectronics, And Nanotechnologies V  Book Series: Proceedings of SPIE-The International Society for Optical Engineering   Volume: 7821, Article Number: 78211J   DOI: 10.1117/12.882045   Published: 2010.

80.Model experimental de carcinogeneză chimică la şoarece - B. Marinescu, Gheorghiţa Isvoranu, Carolina Constantin, C. Coman, Sabina Zurac, C. Căruntu, D. Boda, Monica Neagu, Mihaela Călin, Revista Romana de Medicina Veterinara, vol 20(4), 2010.

81.Tissular and soluble microRNAs for diagnostic improvement and therapy in digestive tract cancers, Radu Albulescu, Monica Neagu, Lucian Albulescu, Cristiana Tanase, Expert Review of Molecular Diagnostics, 11(1), 2011, 101-120

82.Patented Biomarker Panels in Early Detection of Cancer, Monica Neagu, Carolina Constantin, Cristiana Tanase and Daniel Boda, Recent Patents on Biomarkers, 1(1), 2011, 10-24.

83. Application of 3D hydrogel microarrays in molecular diagnostics: advantages and limitations.Tanase CP, Albulescu R, Neagu M. Expert Rev Mol Diagn. 2011 Jun;11(5):461-4. doi: 10.1586/ERM.11.30.

84.Sensitizer localization and immune response in photodynamic therapy of B16 cells, Pop SF , Ion RM , Neagu M, Constantin, C  LASER PHYSICS  Volume: 21   Issue: 3   Pages: 576-581   DOI: 10.1134/S1054660X11050239   Published: MAR 2011

85.The role of confocal microscopy in the dermato-oncology practice. Diaconeasa A, Boda D, Neagu M, Constantin C, Căruntu C, Vlădău L, Guţu D J Med Life. 2011 Jan-Mar;4(1):63-74. Epub 2011 Feb 25.

86.Imaging Studies of Tetra-Sulphonated Porphyrin in K562 Human Chronic Myeloid Leukemia Cells During Photodynamic Therapy, Simona-Florentina Pop, Monica Neagu, Carolina Constantin, Rodica- Mariana Ion, Journal of International Scientific Publications: Materials, Methods & Technology, 2011/6/1

87.Biomedical Materials Based on Fullerenes, Radu Claudiu Fierascu, Irina Dumitriu, Rodica Mariana Ion, Raluca Ioana Bunghez, Monica Neagu, Carolina Constantin, Crina Stavaru, Scientific Study & Research Chemistry & Chemical Engineering, Biotechnology, Food Industry, 2011, 12 (2), pp. 147 – 154

88. Research Highlights, Neagu M, Radu Albulescu, Cristiana Tanase, Biomarkers In Medicine, Vol. 6(2), 197-200, 2012

89. Transcriptomics in Cancer - Stages Toward Patents in Biomarkers? Monica Neagu and Daniel Boda,  Recent Patents on Biomarkers
Volume 2, Number 2, May 2012, Pp.75-82

90. Synthesis, photophysical and cytotoxicity evaluation of A3B type mesoporphyrinic compounds, Luís F. Vieira Ferreira, Diana P. Ferreira, Anabela S. Oliveira, Rica Boscencu, Radu Socoteanu, Mihaela Ilie, Carolina Constantin, Monica Neagu, Dyes and Pigments, Volume 95, Issue 2, Pages 296-303 (November 2012).

91.Photodynamic Properties of Aluminium Sulphonated Phthalocyanines in Human Displazic Oral Keratinocytes Experimental Model C. Matei, M. Tampa, R.M. Ion, M. Neagu, C. Constantin, Digest Journal of Nanomaterials and Biostructures Vol. 7, No. 4, October -December 2012, p. 1535-1547

92.C-terminal peptide of prothymosine alpha detected by SELDI-ToF-MS affinity capture technology, M. Neagu, C. Constantin, D. Popescu, A. D. Iancu, D. L. Radu, H. Kalbacher, O. Tsitsiloni & W. Voelter, Immunology, 2012 vol 137, issue supl s1, page 655

93. Matrix metalloproteinases underexpression in melanoma with regression S. Zurac, G. Negroiu, S. Petrescu, I. Tudose, R. Andrei, T. Tebeica, C. Popp, C. Solovan, M. Neagu, C. Constantin, F. Staniceanu, Virchows Arch (2012) 461 (Suppl 1):S1–S332

94.Spectrum of morphologic alterations of regression in cutaneous melanoma--potential for improving disease prognosis, Zurac S, Negroiu G, Petrescu S, Andrei R, Tebeica T, Popp C, Musţată R, Neagu M, Constantin C, Solovan C, Chiţu V, Reboşapcă A, Andreescu B, Marinescu I, Stăniceanu F. Rom J Intern Med. 2012 Apr-Jun;50(2):145-53

95.The Effects of Photodynamic Therapy in Biological Systems, M. Tampa, Clara Matei, Monica Neagu, Simona-Roxana Georgescu, Acta Medica Transilvanica December 2012;2(4):313-315

96.The C-terminal decapeptide of prothymosin α is responsible for its stimulatory effect on the functions of human neutrophils in vitro. Samara P, Ioannou K, Neagu M, Arnogiannaki N, Ardavanis A, Voelter W, Tsitsilonis O. Int Immunopharmacol. 2013 Jan;15(1):50-7. doi: 10.1016/j.intimp.2012.11.011. Epub 2012 Nov 29.

97.Highlights: Highlights from the latest articles in biomarkers in medicine.Neagu M, Albulescu R, Tanase C.Research Biomark Med. 7(2):201-204, 2013.

98.The role of porphyrin precursor-based photodynamic therapy in dermatology Matei C, Tampa M, Georgescu S-R, Sarbu I, Ion R-M, Constantin C, Neagu M, Medicine in evolution, XIX (1): 38-44, 2013, ISSN 2065-376X

99.5-aminolevulinic acid photodynamic therapy in the treatment of cutaneous squamous cell carcinoma in situ (Bowen’s disease), Tampa M, Matei C, Georgescu S-R, Benea V, Sarbu I, Ion R-M, Constantin C, Neagu M, Popescu S, Medicine in evolution, XIX (1): 45-50, 2013, ISSN 2065-376X

100.Zinc Trisulphonated Phthalocyanine Used in Photodynamic Therapy of Dysplastic Oral Keratinocytes, Mircea Tampa, Clara Matei, Sanda Popescu, Simona-Roxana Georgescu, Monica Neagu, Carolina Constantin, Rodica-Mariana Ion, Rev. Chim. (Bucharest), 64(6), 639-645, 2013.

101.Therapy Targets in Gliobastoma and Cancer Stem Cells: Lessons from Hematopoietic Neoplasms, Maria Linda Cruceru, Monica Neagu, Jean-Baptiste Demoulin, and Stefan N. Constantinescu, Journal of Cellular and Molecular Medicine, vol 17, issue 8, 2013, doi: 10.1111/jcmm.1212295.

102.Immunomics in skin cancer - improvement in diagnosis, prognosis and therapy monitoring, Amanda Bulman, Monica Neagu, Carolina Constantin, Current Proteomics, Volume 10, Number 3, 202 – 217, 2013.

103.Immune parameters in prognosis and therapy monitoring of cutaneous melanoma patients - experience, role and limitations, Monica Neagu, Carolina Constantin, Sabina Zurac,BioMed Research International, special issue Molecular Biomarkers: Tools of Medicine (MBTM) Volume 2013, 15 November 2013 Article ID 107940.

104.Whole body microwave irradiation for improved dacarbazine therapeutical action in cutaneous melanoma mouse model, Monica Neagu, Carolina Constantin,Diana Martin,Lucian Albulescu, Nicusor Iacob, Daniel Ighigeanu, Radiology Research and Practice, Radiology Research and Practice, vol. 2013, Article ID 414816, 10 pages, 2013. doi:10.1155/2013/414816

105.Increased number of fractionated irradiation sessions does not improve the cellular response to methyl aminolevulinate-mediated photodynamic Therapy, Calin Mihaela Antonina, Calin Marian Romeo, Petrescu Emil, Neagu Monica, Photodiagnosis and Photodynamic Therapy (2013) 10, 526—534.

106. Signal transduction molecule patterns indicating potential glioblastoma therapy approaches Cruceru ML, Enciu AM, Popa AC, Albulescu R, Neagu M, Tanase CP, Constantinescu SN, Onco Targets Ther. 2013 Nov 29;6:1737-49.

107.Highlights in Melanoma Biomarkers, Neagu M, Constantin C, Biomark Med. 8(5), 617-619, 2014.

108. Protein microarray for complex apoptosis monitoring of dysplastic oral keratinocytes in experimental photodynamic therapy, Clara Matei, Mircea Tampa, Constantin Caruntu, Rodica-Mariana Ion, Simona-Roxana Georgescu, Georgiana Roxana Dumitrascu, Carolina Constantin and Monica Neagu, Biol Res, 2014, 47(1): 33-41

109.. Biotechnological Advances for Diagnosis of Peripheral Diabetic Neuropathy, Constantin Caruntu, Carolina Negrei, Daniel Boda, Carolina Constantin, Ana Caruntu, Monica Neagu, Roum Biotechnological Letters - Vol. 19, No.6, 9846- 9858, 2014.

110. Circulating biomarker panels for targeted therapy in brain tumors.Tanase C, Albulescu R, Codrici E, Popescu ID, Mihai S, Enciu AM, Cruceru ML, Popa AC, Neagu AI, Necula LG, Mambet C, Neagu M.Future Oncol. 2014 Sep 22:1-14.

111. Wound Repair - Up-Dates in Dressing Patents and Regeneration Biomarkers, Carolina Constantin, Georgeta Paunica-Panea, Vlad D. Constantin and Monica Neagu, Recent Patents on Biomarkers, 2014, 4(3): 133-149.

112. Proteomics focusing on immune markers in psoriatic arthritis, Constantin Caruntu, Daniel Boda, Georgiana Dumitrascu, Carolina Constantin, Monica Neagu, Biomark Med. 2015;9(6):513-28

113. Fluorescent Porphyrin with an Increased Uptake in Peripheral Blood Cell Subpopulations from Colon Cancer Patients.Constantin C, Neagu M. Med Chem. 2015;11(4):354-63

114. Inflammation markers in cutaneous melanoma - edgy biomarkers for prognosis, Monica Neagu, Carolina Constantin, Georgiana Roxana Dumitrascu, Andreea Roxana Lupu, Costin Caruntu, Daniel Boda, Sabina Zurac, Discoveries, 2015, Jan-Mar, 3(1): e38114.

115. Chemokines in the Melanoma Metastasis Biomarkers Portrait. Neagu M, Constantin C, Longo C.J Immunoassay Immunochem. 2015;36(6):559-66.

116.Biotechnology Landscape in Cancer Drug Discovery, Monica Neagu, Radu Albulescu, Cristiana Tanase, Future Science Open, 2015 Pages 1-4.

117.The relationship between interleukin 8 and Ki67 in cutaneous malignant melanoma, Amalia-Elena Anghel, Corina-Daniela Ene, Monica Neagu, Ilinca Nicolae, HVM Bioflux, Volume 7, Issue 3, 149-154, 2015.

118.Interleukin 8 - Major Player in Cutaneous Melanoma Metastasis Process, Amalia-Elena Anghel, Corina-Daniela Ene, Ilinca Nicolae, Vlad Andrei Budu, Carolina Constantin, Monica Neagu, Roum Biotechnological Letters, 2015 (in press)

119.Monitoring diabetic nephropathy by circulating gangliosides, Corina Daniela Ene, Mircea Penescu, Amalia Anghel, Monica Neagu, Vlad Budu, Ilinca Nicolae, J Immunoassay Immunochem. 2015 Sep 11. [Epub ahead of print]

120. 25-OH Vitamin D and Interleukin-8 Emerging Biomarkers in Cutaneous Melanoma Development and Progression, Corina-Daniela Ene, Amalia-Elena Anghel, Monica Neagu and Ilinca Nicolae, Mediators of Inflammation, pages 1-8, Article ID 904876, 2015.

121. Cellular impedance measurement – novel method for in vitro investigation of drug efficacy, Mircea Tampa, Clara Matei, Constantin Caruntu, Teodor Poteca, Dana Mihaila, Simona-Roxana Georgescu, Carolina Constantin, Monica Neagu, Farmacia, October (in press)

 

Funding data

References

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