CoChat
Sign Up
Cited by 150CAR-T cell therapy researchImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

Point-of-care CAR T-cell production (ARI-0001) using a closed semi-automatic bioreactor: Experience from an academic phase I clinical trial

Open access
Castella, Maria, Caballero-Baños, Miguel, Ortiz-Maldonado, Valentín, González-Navarro, Europa Azucena, Suñé, Guillermo, Antoñana-Vidósola, Asier, Boronat, Anna, Marzal, Berta +17 more·2020·Frontiers in Immunology
DOI 10.3389/fimmu.2020.00482PMC PMC7259426
Open this paper in CoChat — free accountOpen PDF

Abstract

Development of semi-automated devices that can reduce the hands-on time and standardize the production of clinical-grade CAR T-cells, such as CliniMACS Prodigy from Miltenyi, is key to facilitate the development of CAR T-cell therapies, especially in academic institutions. However, the feasibility of manufacturing CAR T-cell products from heavily pre-treated patients with this system has not been demonstrated yet. Here we report and characterize the production of 28 CAR T-cell products in the context of a phase I clinical trial for CD19+ B-cell malignancies (NCT03144583). The system includes CD4-CD8 cell selection, lentiviral transduction and T-cell expansion using IL-7/IL-15. 27 out of 28 CAR T-cell products manufactured met the full list of specifications and were considered valid products. Ex vivo cell expansion lasted an average of 8.5 days and had a mean transduction rate of 30.6%±13.44. All products obtained presented cytotoxic activity against CD19+ cells and were proficient in the secretion of pro-inflammatory cytokines. Expansion kinetics was slower in patient’s cells compared to healthy donor’s cells. However, product potency was comparable. CAR T-cell subset phenotype was highly variable among patients and largely determined by the initial product. TCM and TEM were the predominant T-cell phenotypes obtained. 38.7% of CAR T-cells obtained presented a TN or TCM phenotype, in average, which are the subsets capable of establishing a long-lasting T-cell memory in patients. An in-depth analysis to identify individual factors contributing to the optimal T-cell phenotype revealed that ex vivo cell expansion leads to reduced numbers of TN, TSCM and TEFF cells, while TCM cells increase, both due to cell expansion and CAR-expression. Overall, our results show for the first time that clinical-grade production of CAR T-cells for heavily pre-treated patients using CliniMACS Prodigy system is feasible, and that the obtained products meet the current quality standards of the field. Reduced ex vivo expansion may yield CAR T-cell products with increased persistence in vivo.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fimmu.2020.00482

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Early memory T cell subsets (naive, stem cell memory, and central memory T cells) are long-lived, possess high self-renewal ability, and exhibit long-term persistence and superior antitumor response in vivo.

    “It is widely accepted that early memory T cell subsets (e.g., naive [TN], stem cell memory [TSCM] and central memory [TCM]T cells), which are long-lived and possess high self-renewal ability, exhibit long-term persistence and superior antitumor response in vivo.17,18,19”

    From Point-of-care manufacturing of anti-CD19 CAR-T cells using a closed production platform: Experiences of an academic in Thailand (2024) · cites this paper as [19]

    The Discussion (page not provided) associates naïve, stem cell memory, and central memory T-cell phenotypes with longer persistence in vivo and higher antitumor efficacy. It does not state that all three subsets are long-lived or have high self-renewal ability, and its association is more qualified than the citing sentence’s categorical wording. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Further analysis of T cell subsets revealed substantial proportions of TSCM and TCM in the majority of cell products.

    “Further analysis of T cell subsets revealed substantial proportions of TSCM and TCM, which are early memory T cells possessing long-term persistence and antitumor activity in vivo, in the majority of cell products, which is consistent with previous studies using a similar platform and reagents.14,19,25”

    From Point-of-care manufacturing of anti-CD19 CAR-T cells using a closed production platform: Experiences of an academic in Thailand (2024) · cites this paper as [19]

    The Results section (T Cell Subset Characterization; page not provided) reports that memory phenotypes predominated in the vast majority of final products, with TCM averaging 31.01% of CAR+ cells. It does not establish substantial TSCM proportions in most products: TSCM averaged 5.26%, and the authors emphasize high variability among patients. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 61 · Cited by 150

Research works printed but not linked: 56

  1. [1]Gill S June CH. Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. Immunol Rev. (2015) 263: 68– 89. 10.1111/imr.12243 25510272 · DOI
  2. [2]Barrett DM Singh N Porter DL Grupp SA June CH. Chimeric antigen receptor therapy for cancer. Annu Rev Med. (2014) 65: 333– 47. 10.1146/annurev-med-060512-150254 24274181 PMC4120077 · DOI
  3. [3]Dai H Wang Y Lu X Han W. Chimeric antigen receptors modified T-cells for cancer therapy. JNCI J Natl Cancer Inst. (2016) 108: djv439. 10.1093/jnci/djv439 26819347 PMC4948566 · DOI
  4. [4]Sadelain M. CAR therapy: the CD19 paradigm. J Clin Invest. (2015) 125: 3392– 400. 10.1172/JCI80010 26325036 PMC4588281 · DOI
  5. [5]Jensen MC Riddell SR. Design and implementation of adoptive therapy with chimeric antigen receptor-modified T cells. Immunol Rev. (2014) 257: 127– 44. 10.1111/imr.12139 24329794 PMC3991306 · DOI
  6. [6]Chang ZL Chen YY. CARs: synthetic immunoreceptors for cancer therapy and beyond. Trends Mol Med. (2017) 23: 430– 50. 10.1016/j.molmed.2017.03.002 28416139 PMC5423782 · DOI
  7. [7]Kochenderfer JN Wilson WH Janik JE Dudley ME Stetler-Stevenson M Feldman SA. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. (2010) 116: 4099– 102. 10.1182/blood-2010-04-281931 20668228 PMC2993617 · DOI · Paper page
  8. [8]Porter DL Levine BL Kalos M Bagg A June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. (2011) 365: 725– 33. 10.1056/NEJMoa1103849 21830940 PMC3387277 · DOI · Paper page
  9. [9]Wang X Popplewell LL Wagner JR Naranjo A Blanchard MS Mott MR. Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. Blood. (2016) 127: 2980– 90. 10.1182/blood-2015-12-686725 27118452 PMC4911862 · DOI
  10. [12]Brentjens RJ Riviere I Park JH Davila ML Wang X Stefanski J. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. (2011) 118: 4817– 28. 10.1182/blood-2011-04-348540 21849486 PMC3208293 · DOI
  11. [13]Kochenderfer JN Dudley ME Carpenter RO Kassim SH Rose JJ Telford WG. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood. (2013) 122: 4129– 39. 10.1182/blood-2013-08-519413 24055823 PMC3862276 · DOI
  12. [14]Kochenderfer JN Dudley ME Kassim SH Somerville RPT Carpenter RO Stetler-Stevenson M. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. (2015) 33: 540– 9. 10.1200/JCO.2014.56.2025 25154820 PMC4322257 · DOI · Paper page
  13. [15]Brudno JN Maric I Hartman SD Rose JJ Wang M Lam N. T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol. (2018) 36: 2267– 80. 10.1200/JCO.2018.77.8084 29812997 PMC6067798 · DOI
  14. [16]Ali SA Shi V Maric I Wang M Stroncek DF Rose JJ. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood. (2016) 128: 1688– 700. 10.1182/blood-2016-04-711903 27412889 PMC5043125 · DOI
  15. [17]Zhao W-H Liu J Wang B-Y Chen Y-X Cao X-M Yang Y. A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. J Hematol Oncol. (2018) 11: 141. 10.1186/s13045-018-0681-6 30572922 PMC6302465 · DOI
  16. [18]Ramos CA Ballard B Zhang H Dakhova O Gee AP Mei Z. Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. J Clin Invest. (2017) 127: 3462– 71. 10.1172/JCI94306 28805662 PMC5669573 · DOI
  17. [19]Wang C-M Wu Z-Q Wang Y Guo Y-L Dai H-R Wang X-H. Autologous T cells expressing CD30 chimeric antigen receptors for relapsed or refractory hodgkin lymphoma: an open-label phase I trial. Clin Cancer Res. (2017) 23: 1156– 66. 10.1158/1078-0432.CCR-16-1365 27582488 · DOI
  18. [20]Fry TJ Shah NN Orentas RJ Stetler-Stevenson M Yuan CM Ramakrishna S. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. (2017) 24: 20– 8. 10.1038/nm.4441 29155426 PMC5774642 · DOI
  19. [21]Kershaw MH Westwood JA Parker LL Wang G Eshhar Z Mavroukakis SA. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res. (2006) 12: 6106– 15. 10.1158/1078-0432.CCR-06-1183 17062687 PMC2154351 · DOI
  20. [22]O'Rourke DM Nasrallah MP Desai A Melenhorst JJ Mansfield K Morrissette JJD. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. (2017) 9: eaaa0984. 10.1126/scitranslmed.aaa0984 28724573 PMC5762203 · DOI
  21. [23]Katz SC Burga RA McCormack E Wang LJ Mooring W Point GR. Phase I hepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor-modified T-cell therapy for CEA+ liver metastases. Clin Cancer Res. (2015) 21: 3149– 59. 10.1158/1078-0432.CCR-14-1421 25850950 PMC4506253 · DOI
  22. [24]Beatty GL O'Hara MH Lacey SF Torigian DA Nazimuddin F Chen F. Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial. Gastroenterology. (2018) 155: 29– 32. 10.1053/j.gastro.2018.03.029 29567081 PMC6035088 · DOI
  23. [25]Ahmed N Brawley VS Hegde M Robertson C Ghazi A Gerken C. Human epidermal growth factor receptor 2 (HER2) -specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol. (2015) 33: 1688– 96. 10.1200/JCO.2014.58.0225 25800760 PMC4429176 · DOI · Paper page
  24. [26]Thistlethwaite FC Gilham DE Guest RD Rothwell DG Pillai M Burt DJ. The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity. Cancer Immunol Immunother. (2017) 66: 1425– 36. 10.1007/s00262-017-2034-7 28660319 PMC5645435 · DOI
  25. [27]Morgan RA Yang JC Kitano M Dudley ME Laurencot CM Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. (2010) 18: 843– 51. 10.1038/mt.2010.24 20179677 PMC2862534 · DOI
  26. [28]Lamers CH Sleijfer S van Steenbergen S van Elzakker P van Krimpen B Groot C. Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Mol Ther. (2013) 21: 904– 12. 10.1038/mt.2013.17 23423337 PMC5189272 · DOI
  27. [29]Lamers CHJ Sleijfer S Vulto AG Kruit WHJ Kliffen M Debets R. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol. (2006) 24: e20– 2. 10.1200/JCO.2006.05.9964 16648493 · DOI
  28. [30]Brown CE Alizadeh D Starr R Weng L Wagner JR Naranjo A. Regression of glioblastoma after chimeric antigen receptor T-cell therapy. N Engl J Med. (2016) 375: 2561– 9. 10.1056/NEJMoa1610497 28029927 PMC5390684 · DOI
  29. [31]Knochelmann HM Smith AS Dwyer CJ Wyatt MM Mehrotra S Paulos CM. CAR T cells in solid tumors: blueprints for building effective therapies. Front Immunol. (2018) 9: 1740. 10.3389/fimmu.2018.01740 30140266 PMC6094980 · DOI
  30. [32]Long KB Young RM Boesteanu AC Davis MM Melenhorst JJ Lacey SF. CAR T cell therapy of non-hematopoietic malignancies: detours on the road to clinical success. Front Immunol. (2018) 9: 2740. 10.3389/fimmu.2018.02740 30559740 PMC6287001 · DOI
  31. [33]Hoyos V Savoldo B Quintarelli C Mahendravada A Zhang M Vera J. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia. (2010) 24: 1160– 70. 10.1038/leu.2010.75 20428207 PMC2888148 · DOI
  32. [34]Chmielewski M Abken H. CAR T cells releasing IL-18 convert to T-Bethigh FoxO1low effectors that exhibit augmented activity against advanced solid tumors. Cell Rep. (2017) 21: 3205– 19. 10.1016/j.celrep.2017.11.063 29241547 · DOI
  33. [35]Krenciute G Prinzing BL Yi Z Wu M-F Liu H Dotti G. Gottschalk S. Transgenic expression of IL15 improves antiglioma activity of IL13Rα2-CAR T cells but results in antigen loss variants. Cancer Immunol Res. (2017) 5: 571– 81. 10.1158/2326-6066.CIR-16-0376 28550091 PMC5746871 · DOI
  34. [36]Chmielewski M Abken H. CAR T cells transform to trucks: chimeric antigen receptor-redirected T cells engineered to deliver inducible IL-12 modulate the tumour stroma to combat cancer. Cancer Immunol Immunother. (2012) 61: 1269– 77. 10.1007/s00262-012-1202-z 22274776 PMC11029721 · DOI
  35. [37]Castella M Boronat A Martín-Ibáñez R Rodríguez V Suñé G Caballero M. 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. (2019) 12: 134– 44. 10.1016/j.omtm.2018.11.010 30623002 PMC6319086 · DOI
  36. [38]Sommermeyer D Hudecek M Kosasih PL Gogishvili T Maloney DG Turtle CJ. Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia. (2016) 30: 492– 500. 10.1038/leu.2015.247 26369987 PMC4746098 · DOI
  37. [39]Kwajah MMS Schwarz H. CD137 ligand signaling induces human monocyte to dendritic cell differentiation. Eur J Immunol. (2010) 40: 1938– 49. 10.1002/eji.200940105 20432236 · DOI
  38. [40]Kawalekar OU O'Connor RS Fraietta JA Guo L McGettigan SE Posey AD. Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells. Immunity. (2016) 44: 380– 90. 10.1016/j.immuni.2016.01.021 26885860 PMC13498396 · DOI
  39. [41]Aleksandrova K Leise J Priesner C Melk A Kubaink F Abken H. Functionality and cell senescence of CD4/ CD8-selected CD20 CAR T cells manufactured using the automated CliniMACS Prodigy® platform. Transfus Med Hemotherapy. (2019) 46: 47– 54. 10.1159/000495772 31244581 PMC6558326 · DOI
  40. [42]Marín Morales JM Münch N Peter K Freund D Oelschlägel U Hölig K. Automated clinical grade expansion of regulatory T cells in a fully closed system. Front Immunol. (2019) 10: 38. 10.3389/fimmu.2019.00038 30778344 PMC6369367 · DOI
  41. [43]Wang X Rivière I. Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol Ther Oncolytics. (2016) 3: 16015. 10.1038/mto.2016.15 27347557 PMC4909095 · DOI · Paper page
  42. [44]Zhang W Jordan KR Schulte B Purev E. Characterization of clinical grade CD19 chimeric antigen receptor T cells produced using automated CliniMACS prodigy system. Drug Des Devel Ther. (2018) 12: 3343– 56. 10.2147/DDDT.S175113 30323566 PMC6181073 · DOI · Paper page
  43. [45]Priesner C Aleksandrova K Esser R Mockel-Tenbrinck N Leise J Drechsel K. Automated enrichment, transduction, and expansion of clinical-scale CD62L+ T cells for manufacturing of gene therapy medicinal products. Hum Gene Ther. (2016) 27: 860– 9. 10.1089/hum.2016.091 27562135 PMC5035932 · DOI
  44. [47]Mackall C Fleisher T Brown M Magrath I Shad A Horowitz M. Lymphocyte depletion during treatment with intensive chemotherapy for cancer. Blood. (1994) 84: 2221– 8. 10.1182/blood.V84.7.2221.2221 7919339 · DOI
  45. [48]Fraietta JA Beckwith KA Patel PR Ruella M Zheng Z Barrett DM. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood. (2016) 127: 1117– 27. 10.1182/blood-2015-11-679134 26813675 PMC4778162 · DOI · Paper page
  46. [49]Porter DL Hwang W-T Frey N V Lacey SF Shaw PA Loren AW. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. (2015) 7: 303ra139. 10.1126/scitranslmed.aac5415 26333935 PMC5909068 · DOI · Paper page
  47. [50]Zhu F Shah NN Xu H Schneider D Orentas R Dropulic B CAR-T cell production using the Clinimacs® Prodigy system. Blood. (2016) 128: 5724 10.1182/blood.V128.22.5724.5724 · DOI
  48. [51]Mock U Nickolay L Philip B Cheung GWK Zhan H Johnston ICD. Automated manufacturing of chimeric antigen receptor T cells for adoptive immunotherapy using CliniMACS prodigy. Cytotherapy. (2016) 18: 1002– 11. 10.1016/j.jcyt.2016.05.009 27378344 · DOI · Paper page
  49. [52]Blaeschke F Stenger D Kaeuferle T Willier S Lotfi R Kaiser AD. 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. (2018) 67: 1053– 66. 10.1007/s00262-018-2155-7 29605883 PMC11028239 · DOI · Paper page
  50. [53]Blaeschke F Kaeuferle T Feucht J Weber D Lotfi R Kaiser A Defined central memory and stem memory T cell phenotype of CD4 and CD8 CAR T cells for the treatment of CD19+ acute lymphoblastic leukemia in an automated closed system. Blood. (2016) 128: 1053– 66. 10.1182/blood.V128.22.4558.4558 PMC11028239 29605883 · DOI
  51. [54]Hollyman D Stefanski J Przybylowski M Bartido S Borquez-Ojeda O Taylor C. Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy. J Immunother. (2009) 32: 169– 80. 10.1097/CJI.0b013e318194a6e8 19238016 PMC2683970 · DOI
  52. [55]Gomes-Silva D Mukherjee M Srinivasan M Krenciute G Dakhova O Zheng Y. Tonic 4-1BB costimulation in chimeric antigen receptors impedes T cell survival and is vector-dependent. Cell Rep. (2017) 21: 17– 26. 10.1016/j.celrep.2017.09.015 28978471 PMC5645034 · DOI
  53. [57]Hinrichs CS Borman ZA Gattinoni L Yu Z Burns WR Huang J. Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy. Blood. (2011) 117: 808– 14. 10.1182/blood-2010-05-286286 20971955 PMC3035075 · DOI
  54. [58]Berger C Jensen MC Lansdorp PM Gough M Elliott C Riddell SR. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J Clin Invest. (2008) 118: 294– 305. 10.1172/JCI32103 18060041 PMC2104476 · DOI
  55. [59]Larbi A Fulop T From “truly naïve” to “exhausted senescent” T cells: when markers predict functionality. Cytom Part A. (2014) 85: 25– 35. 10.1002/cyto.a.22351 24124072 · DOI · Paper page
  56. [60]Leitenberg D Novak TJ Farber D Smith BR Bottomly K. The extracellular domain of CD45 controls association with the CD4-T cell receptor complex and the response to antigen-specific stimulation. J Exp Med. (1996) 183: 249– 59. 10.1084/jem.183.1.249 8551228 PMC2192406 · DOI

Authors
Castella, M., Caballero-Baños, M., Ortiz-Maldonado, V., González-Navarro, E. A., Suñé, G., Antoñana-Vidósola, A., Boronat, A., Marzal, B., Millán, L., Martín-Antonio, B., Cid, J., Lozano, M., García, E., Tabera, J., Trias, E., Perpiña, U., Canals, J. M., Baumann, T., Benítez-Ribas, D., Campo, E., Yagüe, J., Urbano-Ispizua, Á., Rives, S., Delgado, J., & Juan, M.
Affiliations
  • Hospital Clínic de Barcelona (ES)
  • Hospital Sant Joan de Déu Barcelona (ES)
Corresponding author
Juan, Manel
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2020-03-20
Volume
11
Pages
482-482
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2020.00482
PMC
PMC7259426
OpenAlex
W3015507915
Cited by
150
References
61
Citations by year
2026: 25 · 2025: 22 · 2024: 24 · 2023: 28 · 2022: 28 · 2021: 19 · 2020: 4
FWCI
7.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Docusalut (Conselleria de Salut i Consum del Govern de les Illes Balears) (submittedVersion, cc-by)
  • Hispana (submittedVersion, cc-by)
  • RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion)
Funders
Instituto de Salud Carlos III (PI13/00676, PI17/01043, PI18/00775, PICIS14/00122, PIE13/00033)
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
CAR T-cell therapy, point-of-care manufacturing, CliniMACS Prodigy, CD19 CAR, B-cell malignancies, heavily pretreated patients, lentiviral transduction, T cell subsets, T cell exhaustion, product quality standards, cytokine production
MeSH terms
Academic Medical Centers, Adolescent, Adult, Automation, Cells, Cultured, Child, Cytotoxicity, Immunologic, Female, Humans, Immunologic Memory, Male, T-Lymphocytes, T-Lymphocyte Subsets, Immunotherapy, Adoptive, Point-of-Care Systems, Bioreactors, Cell Proliferation, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review