Main Article Content

Ugo Testa
Prof. Patrizia Chiusolo
Dr. Elvira Pelosi
Dr. Germana Castelli
Giuseppe Leone


adults T cell acute lymphoblastic leukemia, CAR-T Cells, T-cell lymphoblastic lymphoma


Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell lymphoid neoplasia and, in some instances, improved disease outcomes. Thus, six FDA-approved commercial CAR-T cell products that target antigens preferentially expressed on malignant B-cells or plasma cells have been introduced in the therapy of B-cell lymphomas, B-ALLs and multiple myeloma.

These therapeutic successes have triggered the application of CAR-T cell therapy to other hematologic tumors, including T-cell malignancies. However, the success of CAR-T cell therapies in T-cell neoplasms was considerably more limited to the existence of some limiting factors, such as the sharing of mutual antigens between normal T-cells and CAR-T cells, and malignant cells, determining fratricide events and severe T-cell aplasia; contamination of CAR-T cells used for CAR transduction with contaminating malignant T-cells. Allogeneic CAR-T products can avoid tumor contamination but raise other problems related to immunological incompatibility.

In spite of these limitations, there has been significant progress in CD7- and CD5-targeted CAR-T cell therapy of T-cell malignancies in the last few years.


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1. Van der Zwet JCG, Cordo V, Cante-Barrett K, Meijerink JPP. Multiomic approaches to improve outcome for T-cell acute lymphoblastic leukemia patients. Adv Biol Reg 2019; 74: 100647.
2. Liu Y, Easton J, Shao Y, Maciaszek J, Wang Z, Wilkinson MR. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet 2017; 49: 1211-1218.
3. Seki M, Kimura S, Isobe T, Yoshida K, Ueno H, Nakajima-Takagi Y. Recurrent SPI1 (PU1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia. Nat Genet 2017; 49: 1274-1281.
4. DuVall AS, Sheade J, Anderson D, Yates SJ, Stock W. Updates in the management of relapsed and refractory acute lymphoblastic leukemia: an urgent plea for new treatment in being answered. JCO Oncol Pract 2022; 18: 479-487.
5. Stuver R, Moskowitz AJ. Therapeutic advances in relapsed and refractory peripheral T-cell lymphoma. Cancer 2023, 15: 589.
6. Liu J, Zhang Y, Guo R, Zhao Y, Sun R, Guo S, Lu W, Zhao M. Targeted CD7 CAR T-cells for treatment of T-lymphocte leukemia and lymphoma and acute myeloid leukemia: recent advances. Fron Immunol 2023; 14: 1170968.
7. Frankel AE, Laver JH, Willigham MC, Burns LJ, Kersey JH, Vallera DA. Therapy of patients with T-cell lymphomas and leukemias using an anti-CD7 monoclonal antibody-ricin a chain immunotoxin. Leukemia Lymphoma 1997; 26: 287-298.
8. Gomes-Silva D, Srinivasan M, Sharma S, Lee CM, Wagner DL, Davis TH. CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies. Blood 2017; 130: 285-296.
9. Depil S, Duchhateau P, Grupp SA, Mufti G, Poirot L. “Off-the-shelf” allogeneic CAR T cells: development and challenges. Nat Rev Drug Discov 2020; 19: 185-199.
10. Xie L, Gu R, Yang X, Qiu S, Xu Y, Mou J, Wang Y, Xing H, Tang K, Tian Z, et al. Universal anti-CD7 antigen on T/CAR-T cells. Blood 2022; 140 (suppl.1): 4535.
11. Hu Y, Zhou Y, Zhang M, Zhao H, Wiei G, Ge W, Cui Q, Mu Q, Chen G, Han L, et al. Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies: a phase I clinical study. Cell Res 2022; 32: 995-1007.
12. Zhang X, Zhou Y, Yang J, Li J, Qiu L, Ge W, Pei B, Chen J, Han L, Ren J, Lu P. A novel universal CD7-targeted CAR-T cell therapy for relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Blood 2022; 140 (suppl.1): 4566-4567.
13. Leedom T, Hamil AS, Pouyanfard S, Govero J, Langland R, Ballard A, Schwarzkopf L, Martens A, Espenchied A, Vinay P, et al. Characterization of WU-CART-007, an allogeneic CD7-targeted CAR-T cell therapy for T-cell malignancies. Blood 2021; 138 (suppl. 1): 703.
14. Ghobadi A, Aldoss I, Maudfe S, Wayne AS, Bhoywani D, Bajhel A, Dholaria B, Faramand R, Mattison R, Rettig M, et al. Phase 1-2 dose-escalation study of anti-CD7 allogeneic CAR-T cell in relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL). HemaSphere 2023; 7 (s3): P356.
15. Li S, Wang X, Yuan Z, Liu L, Luo L, Li Y, Wu K, Liu J, Yang C, Li Z, et al. Eradication of T-ALL cells by CD7-targeted universal CAR-T cells and initial test of ruxolitinib-based CRS management. Clin Cancer Res 2021; 27: 1242-1246.
16. Li S, Wang X, Liu L, Liu J, Rao J, Yuan Z, Gao L, Li Y, Lou L, Li G, et al. CD7 targeted “off-the-shelf” CAR-T demonstrates robust in vivo expansion and high efficacy in the treatment of patients with relapsed and refractory T cell malignancies. Leukemia 2023; in press.
17. Dioiorio C, Murray R, Naniong M, Barrera L, Camblin A, Chukinas J, Coholan L, Edwards A, Fuller T, Gonzalez C, et al. Cytosine base editing enables quadruple-edited allogeneic CART cells for T-ALL. Blood 2022; 140: 619-629.
18. Chiesa R, Georgiadis C, Syed F, Zhou H, Etuk A, Gkazi SA, Preece R, Ottaviano G, Braybrook Y, Chu J, et al. Base-edited CAR7 T cells for relapsed T-cell acute lymphoblastic leukemia. N Engl J Med 2023; 389: 899-910.
19. Png YT, Vinanica N, Kamiya T, Shimasaki N, Coustan-Smith N, Campana D. Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies. Blood Adv 2017; 1: 1248-1260.
20. Kamiya T, WONG D, Png YT, Campana D. A novel method to generate T-cell receptor-deficient chimeric antigen receptor T cells. Blood Adv 2028; 2: 517-528.
21. Wong XFA,Ng J, Zheng S, Ismail R, Qian H, Campana D. Development of an off-the-Sh elf chimeric antigen receptor (CAR)-T cell therapy for T-cell acute lymphoblastic leukemia (T-ALL) without gene editing. Blood 2022; 140 (suppl.1): 2358-2359.
22. M, Chen D Zhang, Fu X, Meng H, Nan F, Sun Z, Yu H, Zhang L, Li L, Li X, et al. Autologous nanobody-derived fratricide-resistant CD7-CAR T-cell therapy for patients with relapsed and refractory T-cell acute lymphoblastic leukemia/lymphoma. Clin Cancer Res 2022; 28: 2830-2843.
23. Pan J, Tan Y, Wang G, Deng B, Ling Z, Song W, Seery S, Zhang Y, Peng S, Xu J, et al. Donor-derived CD7 chimeric antigen receptor T cells for T-cell acute lymphoblastic leukemia: first-in-human, phase I trial. J Clin Oncol 2021; 39: 3340-3351.
24. Tan Y, Pan J, Deng B, Ling Z, Weiliang S, Tian Z, Cao M, Xu J, Duan J, Wang Z, et al. Efficacy and safety of donor-derived CD7 CART cells for r/r T-cell acute lymphoblastic leukemia/lymphoma: interim analysis from a phase 2 trial. Blood 2022; 140 (suppl. 1): 4602-4603.
25. Tan Y, Shan L, Zhao L, Deng B, Ling Z, Zhang Y, Peng S, Xu J, Duan J, Wang Z, et al. Long-term follow-up of donor-derived CD7 CAR-T cell therapy in patients with T-cell acute lymphoblastic leukemia. J Hematol Oncol 2023; 16: 34.
26. Freiwan A, Zoine JT, Crawford JC, Vaidya A, Schattgen SA, Myers JA, Patil SL, Khanlari M, Inaba H, Klco JM, et al. Engineering naturally occurring CD7- T cells for the immunotherapy of hematological malignancies. Blood 2022; 140: 2684-2694.
27. Lu P, Liu Y, Yang J, Zhang X, Yang X, Wang H, Wang L, Wang D, Jin D, Li J, Huang X. Naturally selected CD7 CAR-T therapy without genetic manipulations for T-ALL/LBL: first-in-human phase 1 clinical trial. Blood 2022; 140: 321-334.
28. -Zhang X, Yang J, Li J, Qiu L, Zhang J, Lu Y, Zhao YL, Jin D, Li J, Lu P. Analysis of 60 patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma treated with CD7-targeted chimeric antigen receptor-T cell therapy. Am J Hematol. 2023 Dec;98(12):1898-1908. doi: 10.1002/ajh.27094. Epub 2023 Sep 23. Erratum in: Am J Hematol. 2024 Jan 15;
29. Zhang Y, Li C, Du M, Jiang H, Luo W, Tang L, Kang Y, Xu J, Wu Z, Wang X, et al. Allogeneic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies. Blood Cancer J 2023; 13: 61
30. Jiang J, Chen J, Liao C, Duan Y, Wang Y, Shang K, Huang Y, Tang Y, Gao X, Gu Y, Sun J. Inserting EF1-drivem CD7-sepcific CAR at CD7 locus reduces fratricide and enhances tumor rejection. Leukemia 2023; 37: 1660-1670.
31. Yo J, Jia Y, Tuhin IJ, Tan J, Monty MA, Xu N, Kang L, Li M, Lou X, Zhou M, et al. Feasibility study of a novel preparation strategy for anti-CD7 CAR-T cells with a recombinant anti-CD7 blocking antibody. Mol Ther Oncolyt 2022; 24: 719-728.
32. Watanabe N, Mo F, Zheng R, Ma R, Bray VC, van Leeuwen DG, Sritabal-Ramirez J, Hu H, Wang S, Metha B, et al. Feasibility and preclinical efficacy of CD7-medaited CD7 CAR T cells for T cell malignancies. Mol Ther 2023; 31: 24-34.
33. Dai Z, Mu W, Zhao Y, Jia X, Liu J, Wei Q, Tan T, Zhou J. The rational development of CD5-targeting biepitopic CARs with fully human heavy-chain-only antigen recognition domains. Mol Ther 2021; 29: 2707-2714.
34. Ho LY, Yu SR, Jeong JH, Lee HJ, Cho HJ, Kim HC. Mitigating the CD5 CAR-CD5 interaction enhances the functionality of CD5 CAR-t cells by alleviating the T-cell fratricide. Cancer Res 2023; 83 (suppl. 7): 4086.
35. Dai Z, Mu W, Zhao Y, Cheng J, Lin H, Ouyang K, Jia X, Liu J, Wei Q, Wang M, et al. T cells expressing CD5/CD7 bispecific chimeric antigen receptors with fully human heavy-chain-only domains mitigate tumor antigen escape. Signal Transd Targeted Therapy 2022; 7: 85.
36. Hill LC, Rouce RH, Smith TS, Yang L, Srinivasan M, Zhang H, Perconti S, Mehta B, Dekhova O, Randall J, et al. Safety and anti-tumor activity of CD5 CAR T-cells in patients with relapsed/refractory T-cell malignancies. Blood 2019; 134 (suppl. 1): 199.
37. Rouce RH, Hill LC, Smith TS, Yang L, Boriskie B, Srinivasan M, Zhang H, Perconti S, Mehta B, Dakhova O, et al. Early signals of anti-tumor efficacy and safety with autologous CD5.CAR T-cells in patients with refractory/relapsed T-cell lymphoma. Blood 2021; 138 (suppl.1): 654.
38. Pan J, Tan Y, Shan L, Deng B, Ling Z, Song W, Feng X, Hu G. Phase I study of donor-derived CD5 CAR T cells in patients with relapsed or refractory T-cell acute lymphoblastic leukemia. J Clin Oncol 2022; 40: 7028.
39. Patel RP, Ghilardi G, Porazzi P, Yang S, Qian D, Pajarillo R, Wang M, Zhang Y, Schuster SJ, Barta SK, et al. Clinical development of Senza 5TM CART5: a novel dual population CD5 CRISPR-Cas9 knocked out anti-CD5 chimeric antigen receptor T cell product for relapsed and refractory CD5+ nodal T-cell lymphoma. Blood 2022; 140 (suppl. 1): 1604-1605.
40. Chun I, Kim KH, Chiang YH, Xie W, Lee Y, Pajarillo R, Rotolo A, Shestova O, Hong SJ, Abdel-Mohsen M, et al. CRISPR-Cas9 knock out of CD5 enhances the anti-tumor activity of chiemeric antigen receptor T cells. Blood 2020; 136 (suppl.1): 51-52.
41. Scarfò I, Ormhoj M, Frigault MJ, Castano AP, Lorrey S, Bouffard AA, van Scoyk A, Rodig SJ, Shay AJ, Aster JC, et al. Anti-CD37 chimeric antigen receptor T cells are active against B- and T-cell lymphomas. Blood 2018; 132: 1495-1506.
42. Frigault MJ, Chen YB, Gallagher K, Horick NK, El-Jawahri A, Scarfò I, Wehrli M, Huang L, Casey K, Cook D, et al. Phase 1 study of CD37-directed CAR T cells in patients with relapsed or refractory CD37+ hematologic malignancies. Blood 2021; 138 (suppl.1): 653.
43. Wu CH, Wang L, Yang CY, Wen KW, Hinds B, Gill R, McCormick F, Moasser M, Pincus L, AI Wz. Targeting CD70 in cutaneous T-cell lymphoma using an antibody-drug conjugate in patient-derived xenograft models. Blood Adv 2022; 6: 2290-2299.
44. Iyer SP, Sica A, Ho J, Hu B, Zain J, Prica A, Weng WK, Kim YH, Kodadoust MS, Palomba ML, et al. The cobalt-lym study of CTX 130: a phase 1 dose-escalation study of CD70-targeted allogeneic CRSPS-CAS9-engineered CAR T cells in patients with relapsed/refractory (R/R) T-cell malignancies. HemaSphere 2022; 6: 53.
45. Maciocia PM, Wawrzyniecka PA, Philip B, Ricciardelli I, Akarca AU, Onuoha SC, Legut M, Cole DK, Sewell AK, Gritti G, et al. Targeting the T cell receptor -chain constant region for immunotherapy of T cell malignancies. Nat Med 2017; 23: 1416-1423.
46. Cwynarski K, Iacoboni G, Thoulouili E, Menne T, Irvine D, Balasubramaniam N, Wood L, Stephens C, Shang J, Xue E, et al. First in human study of AUTO4, a TRBC1 targeting CAR T cell therapy in relapsed/refractory TRBC1-positive peripheral T cell lymphoma. Blood 2022; 140 (suppl. 1): 10316-10317.
47. Ureshino H, Kamachi K, Kimura S. Mogamulizumab for the treatment of adult T-cell leukemia/lymphoma. Clin Lymphoma Myeloma Leuk 2019; 19: 326-331.
48. Moore DC, Elmes JB, Shibu PA. Mogamulizumab: an anti-CC chemokine receptor 4 antibody for T-cell lymphomas. Ann Pharmacother 2020; 54: 371-379.
49. Perera LP, Zhang M, Nakagawa M, Petrus MN, Maeda M, Kadin ME, Waldmann TA, Perera PY. Chimeric antigen receptor modified T cells that target chemokine receptor CCR4 as a therapeutic modality for T-cell malignancies. Am J Hematol 2017; 92: 892-901.
50. Watanabe K, Goemz AM, Kuramitsu S, Siurala M, Du T, Agarwal S, Song D, Scholler J, Rotolo A, Posey AD, et al. Identifying highly active anti-CCR4 CAR T cells for the treatment of T-cell lymphoma. Blood Adv 2023; 7: 3416-3430.
51. Maciocia PM, Wawrzienecka PA, Maciocia nC. Burley A, Karpanasamy T, Devereaux S, Heokx M, O’Connor D, Leon T, Rapoz-D’Silva T, et al. Anti-CCR9 chimeric antigen receptor T cells for T-cell acute lymphoblastic leukemia. Blood 2022; 140: 25-37.
52. Xiang J, Devenport JM, Carter AJ, Staser KW, Kim MY, O’Neal J, Ritchey JK, Rettig MP, Gao F, Rettig G, et al. An “off-the-shelf” CD2 universal CAR-T therapy for T-cell malignancies. Leukemia 2023; 37: 2448-2456.
53. Gilsovic-Aplenc T, Diorio C, Chukinas JA, Veliz K, Shestova, Shen F, Nunez-Cruz S, Vincent TL, Miao F, Milone MC, et al. CD38 as a pan-hematologic target for chimeric antigen receptor T cells. Blood Adv 2023; 22: 4418-4430.

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