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In House CAR-T: a review

In-House CAR-T: una revisión



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Martínez Moreno DF. In House CAR-T: a review. Rev. colomb. hematol. oncol. [Internet]. 2025 Jun. 27 [cited 2025 Dec. 5];12(1):195-210. https://doi.org/10.51643/22562915.688

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How to Cite
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Martínez Moreno DF. In House CAR-T: a review. Rev. colomb. hematol. oncol. [Internet]. 2025 Jun. 27 [cited 2025 Dec. 5];12(1):195-210. https://doi.org/10.51643/22562915.688

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Diego Fernando Martínez Moreno,

Médico Especialista en Hematología y Oncología Clínica, Clínica IMAT AUNA, Montería.


CAR-T therapy poses multiple barriers, such as high cost and limited availability of commercially patented products. In different hospital and academic centers, the production of CAR-T “in house” has been developed as an alternative to overcome these obstacles. The objective of this narrative review is to describe the information reported regarding the manufacturing, effectiveness and safety of “in house” or “academic” CAR-T products; Through a non-systematic search of the literature in the NCBI-PUBMED databases, series and case reports were included, as well as Phase I and II studies available in English and Spanish. In this review, reports from Spain, India, Canada, China, Israel, and Brazil have been identified, showing the feasibility of CAR-T production in academic centers with a low frequency of production failures, with favorable clinical results, predictable toxicity profile, and potential significant resource savings. In particular, the development of academic CAR-Ts such as ARI-0001 and its approval for hospital use in Spain opens a great opportunity to improve access to CAR-T therapy in Europe, and potentially in lower-resource countries such as Latin America.


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  1. June C, Sadelain M. Chimeric Antigen Receptor Therapy. N Engl J Med [Internet]. 2018 Jul 5;379(1):64-73. Disponible en: https://doi.org/10.1056/NEJMra1706169 DOI: https://doi.org/10.1056/NEJMra1706169
  2. Kamal-Bahl S, Puckett J, Bagchi I, Miller-Sonet E, Huntington S. Barriers and solutions to improve access for chimeric antigen receptor therapies. Immunotherapy [Internet]. 2022;14(9):741-753. Disponible en: https://doi.org/10.2217/imt-2022-0037. DOI: https://doi.org/10.2217/imt-2022-0037
  3. Westin J, Kersten M, Salles G, Abramson J, Schuster S, et al. Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Am J Hematol [Internet]. 2021 Oct 1;96(10):1295-1312. Disponible en: https://doi.org/10.1002/ajh.26301. DOI: https://doi.org/10.1002/ajh.26301
  4. Mikhael J, Fowler J, Shah N.Chimeric Antigen Receptor T-Cell Therapies: Barriers and Solutions to Access. JCO Oncol Pract [Internet]. 2022 Dec;18(12):800-807. Disponible en: https://doi.org/10.1200/OP.22.00315. DOI: https://doi.org/10.1200/OP.22.00315
  5. Geethakumari P, Ramasamy D, Dholaria B, Berdeja J, Kansagra A. Balancing Quality, Cost, and Access During Delivery of Newer Cellular and Immunotherapy Treatments. Curr Hematol Malig Rep [Internet]. 2021 Aug;16(4):345-356. Disponible en: https://doi.org/10.1007/s11899-021-00635-3. DOI: https://doi.org/10.1007/s11899-021-00635-3
  6. Zhu F, Shah N, Xu H, Schneider D, Orentas R, Dropulic B, Hari P, Keever-Taylor C. Closed-system manufacturing of CD19 and dual-targeted CD20/19 chimeric antigen receptor T cells using the CliniMACS Prodigy device at an academic medical center. Cytotherapy [Internet]. 2018 Mar;20(3):394-406. Disponible en: https://doi.org/10.1016/j.jcyt.2017.09.005.
  7. Lu J, Jiang G. The journey of CAR-T therapy in hematological malignancies. Mol Cancer [Internet]. 2022 Oct 8;21(1):194. Disponible en: https://doi.org/10.1186/s12943-022-01663-0. DOI: https://doi.org/10.1186/s12943-022-01663-0
  8. Feins S, Kong W, Williams E, Milone M, Fraietta J. An introduction to chimeric antigen receptor (CAR) T-cell immunotherapy for human cancer. Am J Hematol [Internet]. 2019 May;94(S1):S3-S9. Disponible en: https://doi.org/10.1002/ajh.25418. DOI: https://doi.org/10.1002/ajh.25418
  9. De Marco R, Monzo H, Ojala P. CAR T Cell Therapy: A Versatile Living Drug. Int J Mol Sci [Internet]. 2023 Mar 27;24(7):6300. Disponible en: https://doi.org/10.3390/ijms24076300. DOI: https://doi.org/10.3390/ijms24076300
  10. Lindner S, Johnson S, Brown C, Wan L. Chimeric antigen receptor signaling: Functional consequences and design implications. Sci Adv [Internet]. 2020 May 20;6(21):eaaz3223. Disponible en: https://doi.org/10.1126/sciadv.aaz3223. DOI: https://doi.org/10.1126/sciadv.aaz3223
  11. Honikel M, Olejniczak S. Co-Stimulatory Receptor Signaling in CAR-T Cells. Biomolecules [Internet]. 2022 Sep 15;12(9):1303. Disponible en: https://doi.org/10.3390/biom12091303. DOI: https://doi.org/10.3390/biom12091303
  12. Benmebarek M, Karches C, Cadilha B, Lesch S, Endres S, Kobold S. Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells. Int J Mol Sci [Internet]. 2019 Mar 14;20(6):1283. Disponible en: https://doi.org/10.3390/ijms20061283. DOI: https://doi.org/10.3390/ijms20061283
  13. Ivica N, Young C. Tracking the CAR-T Revolution: Analysis of Clinical Trials of CAR-T and TCR-T Therapies for the Treatment of Cancer (1997-2020). Healthcare (Basel) [Internet]. 2021 Aug 19;9(8):1062. Disponible en: https://doi.org/10.3390/healthcare9081062. DOI: https://doi.org/10.3390/healthcare9081062
  14. Neelapu S. CAR-T efficacy: is conditioning the key? Blood [Internet]. 2019 Apr 25;133(17):1799-1800. Disponible en: https://doi.org/10.1182/blood-2019-03-900928. DOI: https://doi.org/10.1182/blood-2019-03-900928
  15. Hayden P, Roddie C , Bader P , Basak G , Bonig H, et al. Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA). Ann Oncol [Internet]. 2022 Mar;33(3):259-275. Disponible en: https://doi.org/10.1016/j.annonc.2021.12.003. DOI: https://doi.org/10.1016/j.annonc.2021.12.003
  16. Gajra A, Zalenski A, Sannareddy A, Jeune-Smith Y, Kapinos K , Ankit Kansagra A. Barriers to Chimeric Antigen Receptor T-Cell (CAR-T) Therapies in Clinical Practice. Pharmaceut Med [Internet]. 2022;36(3):163-171. Disponible en: https://doi.org/10.1007/s40290-022-00428-w. DOI: https://doi.org/10.1007/s40290-022-00428-w
  17. Martinez-Cibrian N, Español-Rego M, Pascal M, Delgado J, Ortiz-Maldonado V. Practical aspects of chimeric antigen receptor T-cell administration: From commercial to point-of-care manufacturing. Front Immunol [Internet]. 2022 Sep 27;13:1005457. Disponible en: https://doi.org/10.3389/fimmu.2022.1005457. DOI: https://doi.org/10.3389/fimmu.2022.1005457
  18. Harrison R, Zylberberg E, Ellison S, Levine B. Chimeric antigen receptor-T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods. Cytotherapy [Internet]. 2019 Feb;21(2):224-233. Disponible en: https://doi.org/10.1016/j.jcyt.2019.01.003.
  19. Vormittag P, Gunn R, Ghorashian S, Veraitch F. A guide to manufacturing CAR T cell therapies. Curr Opin Biotechnol [Internet]. 2018 Oct;53:164-181. Disponible en: https://doi.org/10.1016/j.copbio.2018.01.025. DOI: https://doi.org/10.1016/j.copbio.2018.01.025
  20. Wang X, Rivière I. Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol Ther Oncolytics [Internet]. 2016 Jun 15;3:16015. Disponible en: https://doi.org/10.1038/mto.2016.15. DOI: https://doi.org/10.1038/mto.2016.15
  21. Levine B, Miskin J, Wonnacott K, Keir K. Global Manufacturing of CAR T Cell Therapy. Mol Ther Methods Clin Dev [Internet]. 2017 Mar 17;4:92-101. Disponible en: https://doi.org/10.1016/j.omtm.2016.12.006. DOI: https://doi.org/10.1016/j.omtm.2016.12.006
  22. Scholler J, June C. Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells. Sci Transl Med [Internet]. 2012 May 2;4(132):132ra53. Disponible en: https://doi.org/10.1126/scitranslmed.3003761. DOI: https://doi.org/10.1126/scitranslmed.3003761
  23. Harrison R, Zylberberg E, Ellison S, Levine B. Chimeric antigen receptor-T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods. Cytotherapy [Internet]. 2019 Feb;21(2):224-233. Disponible en: https://doi.org/10.1016/j.jcyt.2019.01.003. DOI: https://doi.org/10.1016/j.jcyt.2019.01.003
  24. Zhu F, Shah N, Xu H, Schneider D, Orentas R, Dropulic B, Hari P, Keever-Taylor C. Closed-system manufacturing of CD19 and dual-targeted CD20/19 chimeric antigen receptor T cells using the CliniMACS Prodigy device at an academic medical center. Cytotherapy [Internet]. 2018 Mar;20(3):394-406. Disponible en: https://doi.org/10.1016/j.jcyt.2017.09.005. DOI: https://doi.org/10.1016/j.jcyt.2017.09.005
  25. Blaeschke F, Stenger D, Kaeuferle T, Willier S, Lotfi R, Kaiser A, et al. Induction of a central memory and stem cell memory phenotype in functionally active CD4+ and CD8+ CAR T cells produced in an automated good manufacturing practice system for the treatment of CD19+ acute lymphoblastic leukemia. Cancer Immunol Immunother [Internet]. 2018 Jul;67(7):1053-1066. Disponible en: https://doi.org/10.1007/s00262-018-2155-7. DOI: https://doi.org/10.1007/s00262-018-2155-7
  26. Kaiser A, Assenmacher M, Schröder B, Meyer M, Orentas R, Bethke U, Dropulic B. Towards a commercial process for the manufacture of genetically modified T cells for therapy. Cancer Gene Ther [Internet]. 2015 Mar;22(2):72-8. Disponible en: https://doi.org/0.1038/cgt.2014.78. DOI: https://doi.org/10.1038/cgt.2014.78
  27. Mock U, Nickolay L, Philip B, Weng-Kit Cheung G, Zhan H, Johnston I, et al. Automated manufacturing of chimeric antigen receptor T cells for adoptive immunotherapy using CliniMACS prodigy. Cytotherapy [Internet]. 2016 Aug;18(8):1002-1011. Disponible en: https://doi.org/10.1016/j.jcyt.2016.05.009. DOI: https://doi.org/10.1016/j.jcyt.2016.05.009
  28. Lock D, Mockel-Tenbrinck N, Drechsel K, Barth C, Mauer D, Schaser T, et al. Automated Manufacturing of Potent CD20-Directed Chimeric Antigen Receptor T Cells for Clinical Use. Hum Gene Ther [Internet]. 2017 Oct;28(10):914-925. Disponible en: https://doi.org/10.1089/hum.2017.111. DOI: https://doi.org/10.1089/hum.2017.111
  29. Karulkar A, Jain H, Shah S, Khan A, Jaiswal A. et al. Making Anti-CD19 CAR-T Cell Therapy Accessible and Affordable: First-in-Human Phase I Clinical Trial Experience from India. Blood [Internet]. 2022;140(Supplement 1):4610-4611. Disponible en: https://doi.org/10.1182/blood-2022-168928 DOI: https://doi.org/10.1182/blood-2022-168928
  30. Palani H, Arunachalam A, Yasar M, Venkatraman A, Kulkarni U, Lionel S, et al. Decentralized manufacturing of anti CD19 CAR-T cells using CliniMACS Prodigy®: real-world experience and cost analysis in India. Bone Marrow Transplant [Internet]. 2023 Feb;58(2):160-167. Disponible en: https://doi.org/10.1038/s41409-022-01866-5. DOI: https://doi.org/10.1038/s41409-022-01866-5
  31. Zanetti S, Velasco-Hernandez T, Gutierrez-Agüera F, Díaz V, Romecín P, Roca-Ho H, et al. A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL. Mol Ther [Internet]. 2022 Feb 2;30(2):550-563. Disponible en: https://doi.org/10.1016/j.ymthe.2021.08.033. DOI: https://doi.org/10.1016/j.ymthe.2021.08.033
  32. Jacoby E, Bielorai B, Avigdor A, Itzhaki O,Hutt D, Nussboim V , et al. Locally produced CD19 CAR T cells leading to clinical remissions in medullary and extramedullary relapsed acute lymphoblastic leukemia. Am J Hematol [Internet]. 2018 Dec;93(12):1485-1492. Disponible en: https://doi.org/10.1002/ajh.25274. DOI: https://doi.org/10.1002/ajh.25274
  33. Itzhaki O, Jacoby E, Nissani A, Levi M, Nagler A, Kubi A, et al. Head-to-head comparison of in-house produced CD19 CAR-T cell in ALL and NHL patients. J Immunother Cancer [Internet]. 2020;8(1):e000148. Disponible en: https://doi.org/10.1136/jitc-2019-000148. DOI: https://doi.org/10.1136/jitc-2019-000148
  34. Molostova O, Shelikhova,L, Muzalevsky Y, Kazachenok A, Pershin D, Elena Kurnikova E, et al. Point-of-Care Production of CD19 CAR-T Cells in an Automated Closed-System: Report of First Clinical Experience. Blood [Internet]. 2018;132(Supplement 1):5202. Disponible en: https://doi.org/10.1182/blood-2018-99-118282. DOI: https://doi.org/10.1182/blood-2018-99-118282
  35. Molostova O, Maschan M et al. Local Manufacture of CD19 CAR-T Cells Using an Automated Closed-System: Robust Manufacturing and High Clinical Efficacy with Low Toxicities. Blood [Internet]. 2019;134(Supplement 1):2625. Disponible en: https://doi.org/10.1182/blood-2019-130370. DOI: https://doi.org/10.1182/blood-2019-130370
  36. Yang J, He J, Zhang X, Li J, Wang Z, Zhang Y, et al. Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study. Blood Cancer J [Internet]. 2022 Jul 7;12(7):104. Disponible en: https://doi.org/10.1038/s41408-022-00694-6. DOI: https://doi.org/10.1038/s41408-022-00694-6
  37. Castella M, Boronat A, Martín-Ibáñez R, Rodríguez V, Suñé G, Caballero M, et al. Development of a Novel Anti-CD19 Chimeric Antigen Receptor: A Paradigm for an Affordable CAR T Cell Production at Academic Institutions. Mol Ther Methods Clin Dev [Internet]. 2019 Mar 15;12:134-144. Disponible en: https://doi.org/10.1016/j.omtm.2018.11.010 DOI: https://doi.org/10.1016/j.omtm.2018.11.010
  38. Castella M, Caballero-Baños M, Ortiz-Maldonado V, González-Navarro E, Suñé G, Antoñana-Vidósola A, et al. Point-Of-Care CAR T-Cell Production (ARI-0001) Using a Closed Semi-automatic Bioreactor: Experience From an Academic Phase I Clinical Trial. Front Immunol [Internet]. 2020 Mar 20;11:482. Disponible en: https://doi.org/10.3389/fimmu.2020.00482. DOI: https://doi.org/10.3389/fimmu.2020.00482
  39. Ortíz-Maldonado V, Rives S, Castellà M, Alonso-Saladrigues A, Benítez-Ribas D ,Caballero-Baños M, et al. CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19+ Relapsed/Refractory Malignancies. Mol Ther [Internet]. 2021 Feb 3;29(2):636-644. Disponible en: https://doi.org/10.1016/j.ymthe.2020.09.027. DOI: https://doi.org/10.1016/j.ymthe.2020.09.027
  40. Martínez-Cibrián N, Ortiz-Maldonado V, Español-Rego M, Blázquez A, Cid J, Lozano M, et al. The academic point-of-care anti-CD19 chimeric antigen receptor T-cell product varnimcabtagene autoleucel (ARI-0001 cells) shows efficacy and safety in the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma. Br J Haematol [Internet]. 2023 Oct 31. Disponible en: https://doi.org/10.1111/bjh.19170. DOI: https://doi.org/10.1111/bjh.19170
  41. Ying Z, Yang H, Guo Y, Li W, Zou D, Zhou D, et al. Relmacabtagene autoleucel (relma-cel) CD19 CAR-T therapy for adults with heavily pretreated relapsed/refractory large B-cell lymphoma in China. Cancer Med [Internet]. 2021 Feb;10(3):999-1011. Disponible en: https://doi.org/10.1002/cam4.3686. DOI: https://doi.org/10.1002/cam4.3686
  42. Kekre N, Hay K, Webb J, Mallick R, Balasundaram M, Sigrist M, et al. CLIC-01: Manufacture and distribution of non-cryopreserved CAR-T cells for patients with CD19 positive hematologic malignancies. Front Immunol [Internet]. 2022 Dec 19;13:1074740. Disponible en: https://doi.org/10.3389/fimmu.2022.1074740. DOI: https://doi.org/10.3389/fimmu.2022.1074740
  43. Myers R, Li Y, Leahy A, Barrett D, Teachey D, Callahan C, et al. Humanized CD19-Targeted Chimeric Antigen Receptor (CAR) T Cells in CAR-Naive and CAR-Exposed Children and Young Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia. J Clin Oncol [Internet]. 2021 Sep 20;39(27):3044-3055. Disponible en: https://doi.org/10.1200/JCO.20.03458. DOI: https://doi.org/10.1200/JCO.20.03458
  44. Shohdy K , Pillai M , Guest R , Rothwell D , Kirillova N , Chow S, et al. Evidence of clinical efficacy of a first generation CD19 CAR T cell in B cell malignancies. EJHaem [Internet]. 2023 Jun 24;4(3):882-885. Disponible en: https://doi.org/10.1002/jha2.731. DOI: https://doi.org/10.1002/jha2.731
  45. Kfir-Erenfeld S, Asherie N, Grisariu S, Avni B, Zimran E, Assayag M, et al. Feasibility of a Novel Academic BCMA-CART (HBI0101) for the Treatment of Relapsed and Refractory AL Amyloidosis. Clin Cancer Res [Internet]. 2022 Dec 1;28(23):5156-5166. Disponible en: https://doi.org/10.1158/1078-0432.CCR-22-0637. DOI: https://doi.org/10.1158/1078-0432.CCR-22-0637
  46. Asherie N, Kfir-Erenfeld S, Avni B, Assayag M, Dubnikov T, Zalcman N, et al. Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial. Haematologica [Internet]. 2023 Jul 1;108(7):1827-1839. Disponible en: https://doi.org/10.3324/haematol.2022.281628. DOI: https://doi.org/10.3324/haematol.2022.281628
  47. Oliver-Caldés A, González-Calle V, Cabañas V, Español-Rego M, Rodríguez-Otero P, Reguera J, et al. Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study. Lancet Oncol [Internet]. 2023 Aug;24(8):913-924. Disponible en: https://doi.org/10.1016/S1470-2045(23)00222-X. DOI: https://doi.org/10.1016/S1470-2045(23)00222-X
  48. Guerino-Cunha R, Clé D, Carvalho L, Dermínio C, Oliveira L, Oliveira P, et al. Viability of Chimeric Antigen Receptor T Cell Therapy in Latin America. Blood [Internet]. 2021;138(Supplement 1):4843-4843. Disponible en: https://doi.org/10.1182/blood-2021-154217. DOI: https://doi.org/10.1182/blood-2021-154217
  49. Mitchell D, Kenderian S, Rajkumar V. Letting academic medical centers make CAR-T drugs would save billions. [Internet] [Nov. 20, 2019]. Available from: https://www.statnews.com/2019/11/20/car-t-drugs-academic-medical-centers-save-billions/.
  50. Arnaudo L. On CAR-Ts, decentralized in-house models, and the hospital exception. Routes for sustainable access to innovative therapies. J Law Biosci [Internet]. 2022 Jul-Dec; 9(2):lsac027. Disponible en: https://doi.org/10.1093/jlb/lsac027. DOI: https://doi.org/10.1093/jlb/lsac027
  51. Juan M, Delgado J, Calvo G, Trias E, Urbano-Ispizua A. Is Hospital Exemption an Alternative or a Bridge to European Medicines Agency for Developing Academic Chimeric Antigen Receptor T-Cell in Europe? Our Experience with ARI-0001. Hum Gene Ther [Internet]. 2021 Oct;32(19-20):1004-1007. Disponible en: https://doi.org/10.1089/hum.2021.168. DOI: https://doi.org/10.1089/hum.2021.168
  52. Wang V, Gauthier M, Decot V, Loïc Reppel L, Bensoussan D. Systematic Review on CAR-T Cell Clinical Trials Up to 2022: Academic Center Input. Cancers (Basel) [Internet]. 2023 Feb 4;15(4):1003. Disponible en: https://doi.org/10.3390/cancers15041003. DOI: https://doi.org/10.3390/cancers15041003
  53. Picanço-Castro V, Bonamino M, Ramos R, Guerino-Cunha R, Oliveira T, Rego E, et al. CAR-T cells: preclinical development-Safety and efficacy evaluation. Hematol Transfus Cell Ther [Internet]. 2021;43(S2):S54-S63. Disponible en: https://doi.org/10.1016/j.htct.2021.09.008 DOI: https://doi.org/10.1016/j.htct.2021.09.008
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