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02 February 2025: Review Articles  

A Review of CAR T Cells and Adoptive T-Cell Therapies in Lymphoid and Solid Organ Malignancies

Dinah V. Parums1CDEF*

DOI: 10.12659/MSM.948125

Med Sci Monit 2025; 31:e948125

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Abstract

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ABSTRACT: Chimeric antigen receptor (CAR) T cells are genetically engineered T lymphocytes that express a synthetic receptor that recognizes a tumor cell surface antigen, which causes the T lymphocyte to kill the tumor cell. As of December 2024, the US Food and Drug Administration (FDA) approved six CAR T-cell therapies, with ten CAR T-cell therapies commercially available globally, which target the CD19 and B-cell maturation antigen (BCMA) molecules and with approved indications that include B-cell acute lymphoblastic leukemia (ALL), large B-cell lymphoma (LBCL), follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia (CLL), and multiple myeloma. Pharmaceutical and economic forecasts have shown that the global CAR T-cell therapy market was worth USD 4.6 billion in 2024, with a projected USD 25 billion by 2035. However, there are several challenges in treating hematologic malignancies with CAR T-cell therapy, which include reduced treatment efficacy and durability in some patients, acute and long-term adverse effects, lack of effective salvage treatments, limited access to CAR T-cell therapies due to cost and availability, and the rare association with developing myeloid malignancies. A tumor-infiltrating lymphocyte (TIL) therapy, lifileucel, is FDA-approved for advanced melanoma. The T-cell receptor (TCR) therapy, afamitresgene autoleucel, is FDA-approved for advanced synovial sarcoma. The results from ongoing studies and clinical trials are awaited in solid tumors (melanoma, sarcomas, and carcinomas). This article reviews recent developments and ongoing challenges in adoptive T-cell therapies, including CAR T-cell therapies, in lymphoid and solid organ malignancies.

Keywords: Immunotherapy, Adoptive, Leukemia, Lymphoma, Neoplasms, review

Introduction

Adoptive T-cell therapies for leukemia, non-Hodgkin lymphoma (NHL), melanoma, and, potentially, for sarcoma and carcinoma include chimeric antigen receptor (CAR) T-cell, tumor-infiltrating lymphocytes (TILs), and T-cell receptor (TCR) therapies [1,2]. Interleukin-2 (IL-2) is an established ex vivo method for stimulating and harvesting T cells from human tissue, including tumor tissue [1]. This role for IL-2 has allowed the passive administration of antitumor T cells, or adoptive T-cell therapy, a rapidly developing area of targeted cancer immunotherapy [1]. Adoptive T-cell therapy has several advantages compared to other types of cancer immunotherapy. First, many antitumor T cells can be grown in vitro and then selected for their avidity against the desired tumor-associated antigen [1,2]. Second, the patient can be prepared to provide a suitable tumor microenvironment before the adoptive T-cell treatment [1,2].

The first reported type of adoptive T-cell therapy was for TILs, expanded from human melanoma tissues using IL-2 and administered to the patient [3]. Further developments resulted in techniques for introducing antitumor TCRs into autologous lymphocytes, leading to both TCR and CAR T-cell therapies with antitumor specificity [1,2]. CAR T cells are genetically engineered T lymphocytes that express a synthetic receptor that recognizes a tumor cell surface antigen, which causes the T cell to kill the tumor cell [1,2]. Between 2017 and 2024, the US Food and Drug Administration (FDA) approved six CAR T-cell therapies (Table 1) [1,2,4]. Currently, there are ten CAR T-cell therapies commercially available globally, which target the CD19 and B-cell maturation antigen (BCMA) molecules (Table 1) [2,4]. The approved indications for CAR T-cell therapies include B-cell acute lymphoblastic leukemia (ALL), large B-cell lymphoma (LBCL), follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia (CLL), and multiple myeloma (Table 1) [2,4]. Pharmaceutical and economic forecasts have shown that the global CAR T-cell therapy market was worth USD 4.6 billion in 2024, with a projected USD 25 billion by 2035 [5].

The development of adoptive T-cell therapies has been slow due to several recognized associated adverse events [1,2,6,7]. TIL and TCR T-cell therapies can result in an immune effector cell-associated neurotoxicity syndrome, which includes encephalopathy [6]. Also, TIL and TCR T-cell therapies require administration with high-dose interleukin-2 (IL-2), which can cause fevers and capillary leak syndrome [6]. Capillary leak syndrome presents with fluid retention, pulmonary edema, and renal dysfunction [6]. CAR T-cell therapy can be complicated by cytokine release syndrome, which results in hypotension, hypoxia, and tachycardia [7,8]. Chemotherapy, such as cyclophosphamide and fludarabine, is typically administered before CAR T-cell, TCR, and TIL T cell infusions to deplete other cells that may suppress or compete with the therapeutic T cells [1,2]. Therefore, patients may experience toxicities from standard chemotherapeutic agents and novel adoptive T-cell therapies [7]. The results from ongoing studies and clinical trials are awaited to identify adoptive T-cell therapies for solid tumors (melanoma, sarcomas, and carcinomas). This article reviews recent developments and ongoing challenges in adoptive T-cell therapies, including CAR T-cell therapies, in lymphoid and solid organ malignancies.

What is CAR T-Cell Therapy?

The chimeric antigen receptor (CAR) protein is a synthetic receptor expressed by genetically engineered T cells that binds to an extracellular malignancy-associated antigen on a tumor cell [2,9]. The CAR protein receptor consists of an extracellular antigen-recognition moiety, which is usually derived from the variable regions of an antibody, and intracellular T cell-derived components that activate the T cell, a CD3 T-cell activation domain, and a costimulatory CD28 or 4-1BB domain [9]. Autologous T cells are genetically modified using a viral vector to express the CAR protein on the cell surface [9]. Generic CAR T cell products generally have names with two words, with the first word indicating the gene component and the second describing the cell component [9]. The letters – cabta – in the first word indicate - cell expressed antibody and T-cell activation [9]. Autologous CAR T cell products, derived from the patient, often have two-word names, with the second word starting with auto [9]. The ending of the second word, -cel, indicates that the product is a cellular drug [9].

Currently Approved CAR T-Cell Therapies

Currently, six CAR T-cell therapies are approved by the US Food and Drug Administration (FDA), and an additional four are commercially available globally (Table 1) [2,4). Anti-CD19 CAR T-cell therapy has shown success in patients with B-cell malignancies who previously were refractory to treatments, including B-cell ALL, CLL, LBCL follicular lymphoma, mantle cell lymphoma, and myeloma, and can also achieve long-lasting remissions [2,4].

Tisagenlecleucel (Kymriah), axicabtagene ciloleucel (Yescarta), brexucabtagene autoleucel (Tecartus), and lisocabtagene maraleucel (Breyanzi) are cellular drugs, engineered to recognize the B-cell antigen, CD19, and they treat specific B-cell non-Hodgkin lymphomas, B-cell acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL) [2,4]. Idecabtagene violence (Abecma) and ciltacabtagene autoleucel (cita-cel or Carvykti) target the plasma cell-associated protein B-cell maturation antigen (BCMA) and are used to treat multiple myeloma (Table 1) [2,4]. Tisagenlecleucel (Kymriah), the first commercially available cellular immunotherapy, was FDA-approved in 2017 for children and young adults 25 years and younger with B-cell ALL [2–4]. Regulatory approval was supported by the results from a phase 2 clinical trial of patients with ALL, in which treatment resulted in remission in 82% of patients [3,4]. At a 3-year follow-up, treatment with tisagenlecleucel (Kymriah) resulted in a relapse-free survival rate of 48% [4]. In a retrospective analysis of 511 patients that compared tisagenlecleucel (Kymriah) to usual or standard of care, tsagenlecleucel (Kymriah) significantly improved 2-year overall survival (59.5% vs 36.2%) [10].

Axicabtagene ciloleucel (Yescarta) was evaluated in 101 patients with previously treated large B-cell lymphoma (LBCL), which resulted in a complete remission rate of 54% and 5-year survival rate of 43%, compared with overall survival of 20% at 2 years in a historical control [11,12]. Randomized clinical trial data also supported regulatory approval of axicabtagene ciloleucel (Yescarta) and lisocabtagene maraleucel (Breyanzi) for LBCL in patients who did not have a response to their first standard chemotherapy regimen or who progressed within 12 months of initial remission [13]. The 2-year progression-free survival rates following axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) treatment for follicular lymphoma were 63% and 57%, respectively [8,14]. The 12-month progression-free survival rates following brexucabtagene autoleucel (Tecartus) and lisocabtagene maraleucel (Breyanzi) for mantle cell lymphoma were 61% and 53%, respectively [15,16]. In patients with multiple myeloma with a median of six prior cancer treatments, idecabtagene vicleucel (Abecma) was associated with a response rate of 73%, and ciltacabtagene autoleucel (cita-cel or Carvykti) had a response rate of 98% [17,18]. Two randomized clinical trials comparing anti-BCMA CAR T-cell therapy with Idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (cita-cel or Carvykti) compared standard-of-care treatments for patients with previously treated multiple-myeloma, and prior treatment showed superior progression-free survival with CAR T-cell therapy [19–21]. However, there are several challenges in treating hematologic malignancies with CAR T-cell therapy, which include reduced treatment efficacy and durability in some patients, acute and long-term adverse effects, lack of effective salvage treatments, limited access to CAR T-cell therapies due to cost and availability, and the rare association with developing myeloid malignancies [22–24].

Reasons for Reduced Efficacy of CAR T-Cell Therapy

The reduced efficacy of CAR T-cell therapy in some patients and the lack of durable remission may be explained by acquired antigen escape mechanisms, which may explain treatment relapse. As B-cell malignancy progresses, it either no longer expresses the antigen targeted by the CAR T cell, has reduced target antigen expression, or expresses the antigen in an altered form not recognized by CAR T cells. These antigen escape mechanisms could explain many patients with relapse after initial remission following CAR T-cell therapy [25,26]. The low efficacy of CAR T-cell therapy could also be explained by the poor quality of the autologous T cells harvested from the patient during leukapheresis, resulting in reduced quality of manufactured CAR T cells, as treatment response rates are improved with more immature T cells with increased proliferation rates following transfer [25,26]. Also, patients with more prior cancer treatments are at risk for functionally impaired T cell responses and are less likely to achieve remissions [26,27]. Methods for identifying patients at risk for antigen escape and impaired treatment efficacy are essential, as resistance to CAR T-cell therapy is associated with poorer patient treatment outcomes.

Acute and Long-Term Adverse Effects of CAR T-Cell Therapy

CAR T-cell therapy can be complicated by cytokine release syndrome that includes hypotension, hypoxia, and tachycardia [7,8,28]. TIL and TCR T-cell therapies can result in an immune effector cell-associated neurotoxicity syndrome [7,8]. High-dose IL-2 is given with TIL and TCR T-cell therapies, which can cause fevers and capillary leak syndrome [7,8]. Anti-CD19 CAR T cells can proliferate in the patient, sometimes by as much as 1,000-fold, which increases the levels of several cytokines, including IL-6 and interferon-γ, and inflammatory factors [7,8,28]. Increased levels of circulating proinflammatory factors result in cytokine release syndrome, which presents as fever, hypotension, and coagulopathies [7,8,28]. Cytokine release syndrome can be reduced by administering the IL-6 blocker, tocilizumab, after symptoms develop, which supports the recent FDA approval of tocilizumab for CAR T cell-mediated cytokine release syndrome [7,8,28]. Dexamethasone or prednisone can be administered as second-line agents to treat cytokine release syndrome and reduce the effects [28]. However, CAR T cells can cross the blood-brain barrier to cause permanent neurologic syndromes, including encephalopathy, dysphasia, tremors, focal motor defects, cerebral edema, and seizures [7,8,28]. This condition is termed immune effector cell-associated neurotoxicity syndrome and is recognized by a consensus committee from the American Society for Transplantation and Cellular Therapy, which has developed a system for grading this CAR T-cell therapeutic toxicity [29]. Also, several professional societies have published guidelines for managing cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome [30–32].

Cytokine release syndrome and neurologic toxicities require specialized medical management, which means that CAR T-cell therapy is currently administered at tertiary care centers, and only 9–24% of patients receive outpatient CAR T cell infusions in clinical trials [33]. Clinical trial data have shown that long-term adverse effects of CAR T-cell therapy include prolonged myelosuppression, which affects 22–54% of patients, and immunosuppression, which may result in opportunistic infections infection in 5–32% of patients [33]. Anti-CD19 CAR T-cell therapies, including tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta), may eliminate normal CD19-expressing B lymphocytes, leading to complete B-cell depletion (B-cell aplasia), resulting in hypogammaglobulinemia, which requires immunoglobulin replacement therapy [34]. Patients with B-cell aplasia and prolonged cytopenias are at increased risk of opportunistic and primary pathogen infections, most commonly reported during the month following anti-CD19 CAR T cell infusion [35].

Secondary Myeloid Malignancies and CAR T-Cell Therapy

Myelodysplasia and secondary myeloid malignancies, including acute myeloid leukemia (AML), affect approximately 2–10% of patients within five years after treatment with CAR T cells [22–24,36]. Prior chemotherapy and chemotherapy received immediately before a CAR T cell infusion will also result in an increased risk for myelodysplasia and AML [22–24]. However, in recognition of these associations, in December 2023, the FDA approved an updated package insert box warning for ciltacabtagene autoleucel (cita-cel or Carvykti), which states that secondary hematologic malignancies, including AML and myelodysplastic syndrome, had been reported in patients treated with this CAR T-cell product [37,38]. The potential for CAR T-cell therapy to increase the risk of subsequent T-cell malignancies is unknown and remains under investigation [38]. However, thousands of patients have received CAR T-cell therapy for potentially life-threatening hematologic malignancies, and these toxicities are rare, so the benefit of CAR T-cell therapy is still considered to outweigh the risk [38].

CAR T-Cell Therapy for Solid Malignant Tumors

The development of CAR T-cell therapy for solid malignant tumors has been slow and difficult for several reasons. There are limited numbers of identified antigens specifically expressed on the surface of malignant epithelial and mesenchymal cells that can be targeted by CARs [38,39]. Also, many antigens share expression by tumor cells and healthy cells [38,39]. However, recent studies have supported the development of CAR T-cell therapy for patients with solid malignant tumors [38–40]. Recently, CAR T cells directed against disialoganglioside GD2 showed responses in 17/27 (63%) children with pediatric neuroblastoma, identified according to revised International Neuroblastoma Response Criteria [41]. Early results from treatment directed at prostate-specific antigen (PSA) in patients with advanced prostate carcinoma showed reduced PSA levels following treatment [42]. Because carcinomas and sarcomas can be localized on imaging, locoregional CAR T-cell therapies are being developed, which may reduce CAR T-cell toxicity [43,44].

Tumor-Infiltrating Lymphocytes (TILs)

Lifileucel (Amtagvi) is an adoptive immune cell therapy that uses autologous ex vivo-expanded tumor-infiltrating lymphocytes (TILs) [45]. On February 16, 2024, the US Food and Drug Agency (FDA) granted accelerated approval for lifileucel for adult patients with advanced or unresectable melanoma progressing after treatment with immune checkpoint inhibitors and, if BRAF V600 mutation-positive, BRAF/MEK inhibitors [45,46]. However, the manufacturing process, the requirements for patient selection, and the pretreatment lymphodepletion regimen are followed by a single infusion of lifileucel and up to six treatments with high-dose IL-2 [45]. The use of this TIL therapy has the potential for adverse events at each stage of treatment [45,47]. Following the first US FDA-approved TIL cell therapy product, lifileucel (Amtagvi), the supporting clinical trials have identified potential adverse events [47]. Adoptive cell therapy with autologous, ex vivo-expanded TILs is a complex, time-consuming, and potentially costly new type of immunotherapy [6,47].

In 2024, expert consensus guidelines were published on best practices and patient management for adoptive cell therapy with autologous, ex vivo-expanded TILs [47]. An international TIL Working Group was formed in anticipation of further regulatory approvals for clinical use [47]. The consensus guidelines have been developed for multidisciplinary teams of physicians, nurses, and other healthcare professionals involved in patient care [47]. This approach to treating advanced-stage solid malignant tumors has shown efficacy and tolerable safety in clinical trials, with advances in the central manufacturing process [47]. The new guidelines and oversight by the TIL Working Group aim to provide and update recommendations for patient treatment eligibility criteria, management, screening tests and clinical and toxicity management, tumor tissue procurement, lymphodepletion, IL-2 administration, and TIL infusion, to develop a standard of care for adoptive cell therapies [47].

TIL Therapy and Solid Malignant Tumors

Cellular therapy for solid tumors has primarily been with TILs, natural T cells grown ex vivo from a resected tumor [3,48]. The TIL therapy, lifileucel (LN-145) (Amtagvi), received accelerated FDA approval to treat unresectable or metastatic melanoma in patients previously treated with at least one systemic therapy [46]. FDA approval was based on an overall response rate of 31.5% (95% CI, 21.1–43.4%) and the median duration of response that was not reached [46]. Tumor responses were reported with TIL therapy for human papillomavirus (HPV)-associated cancers, with responses in 5/18 patients (28%) with cervical cancer and 2 of 11 patients (18%) with other HPV-associated cancers, including oropharyngeal cancer [49]. In August 2019, the FDA granted a Breakthrough Therapy designation for lifileucel (LN-145) (Amtagvi) as a cervical cancer treatment based on the results from a phase 2 study of adoptive cell transfer using autologous TILs for the treatment of recurrent, metastatic, or persistent cervical cancer [3,50].

TCR T-Cell Therapy and Solid Malignant Tumors

T-cell receptor (TCR)-engineered T-cell therapies involve administering T cells that are genetically engineered ex vivo to express a TCR that targets a tumor-associated antigen [51]. The TCR T-cell therapy afamitresgene autoleucel (afami-cel) (Tecelra) has received FDA approval for treating synovial cell sarcoma after prior chemotherapy [51,52]. Afamitresgene autoleucel (afami-cel) (Tecelra) targets the antigen melanoma-associated antigen A4 (MAGE-A4). FDA approval was based on an overall response rate of 39% (median duration of response, 11.6 months) [52,53]. Other TCR T-cell therapies have antitumor effects exhibited by tumor responses in early-phase clinical trials for synovial cell sarcoma, melanoma, and HPV-associated cancers directed to the HPV oncoproteins [54,55].

Future Developments: CAR NK Cells

Natural killer (NK) cells are fundamental to the innate immune response. NK cells possess independent cytotoxic capabilities that are pivotal in combating cancer. Developments in treatments for solid malignancies that target T-cell immunity have been slow, which highlights the importance of developing innovative approaches, which may include roles for NK cells, including chimeric antigen receptor (CAR) NK cells [56]. There are still some unknowns regarding the dynamics of NK cells within the tumor microenvironment [56]. However, there are potential applications for emerging CAR NK cell therapeutic strategies in precision medicine and cancer treatment [56].

Conclusions

In less than a decade, adoptive T-cell therapies have progressed from targeting B-cell leukemias and lymphomas to melanoma, and there is now the potential for targeting sarcomas and carcinomas. CAR T-cell therapy is a regulatory-approved immunotherapy that has currently shown improved progression-free survival in patients with multiple myeloma, improved overall survival for patients with DLBCL, and high rates of remission in patients with other hematologic malignancies, including ALL, follicular lymphoma, and mantle cell lymphoma. Recently approved T lymphocyte-based immunotherapies are showing potential for improved outcomes in patients with solid tumor malignancies. Although the potential for CAR T-cell, TIL, and TCR T-cell therapies are now becoming realized, so is their potential for significant and generalized treatment complications, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and capillary leak syndrome. Therefore, drug development should continue in parallel with an increased understanding of the prevention, diagnosis, and management of these complications and the use of guidelines for therapeutic monitoring of adoptive T-cell therapy.

References

1. Feldman SA, Assadipour Y, Kriley I, Adoptive cell therapy – tumor-infiltrating lymphocytes, T-cell receptors, and chimeric antigen receptors: Semin Oncol, 2015; 42(4); 626-39

2. Mavi AK, Gaur S, Gaur G, CAR T-cell therapy: Reprogramming patient’s immune cell to treat cancer: Cell Signal, 2023; 105; 110638

3. Rosenberg SA, Speiss P, Lafreniere R, A new approach to adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes: Science, 1986; 233; 1318-21

4. National Cancer Institute (NCI): CAR T Cells: Engineering patients’ immune cells to treat their cancers March, 2022 Available from: https://www.cancer.gov/about-cancer/treatment/research/car-t-cells

5. Research and Markets Forecast: CAR T cell therapy market: Industry trends and global forecasts, till 2035: Distribution by target indication, target antigens, key geographical regions, key players and sales forecast May, 2024 Available from: https://www.researchandmarkets.com/report/car-t-therapies

6. Chesney J, Lewis KD, Kluger H, Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: Pooled analysis of consecutive cohorts of the C-144-01 study: J Immunother Cancer, 2022; 10(12); e005755

7. Brudno JN, Kochenderfer JN, Toxicities of chimeric antigen receptor T cells: Recognition and management: Blood, 2016; 127(26); 3321-30

8. Brudno JN, Kochenderfer JN, Current understanding and management of CAR T cell-associated toxicities: Nat Rev Clin Oncol, 2024; 21(7); 501-21

9. Loizides U, Dominici M, Manderson T, The harmonization of World Health Organization International Nonproprietary Names definitions for cell and cell-based gene therapy substances: When a name is not enough: Cytotherapy, 2021; 23(5); 357-66

10. Stackelberg VA, Jäschke K, Jousseaume E, Tisagenlecleucel vs. historical standard of care in children and young adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia: Leukemia, 2023; 37(12); 2346-55

11. Neelapu SS, Jacobson CA, Ghobadi A, Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma: Blood, 2023; 141(19); 2307-15

12. Crump M, Neelapu SS, Farooq U, Outcomes in refractory diffuse large B-cell lymphoma: Results from the international SCHOLAR-1 study: Blood, 2017; 130(16); 1800-8

13. Westin JR, Oluwole OO, Kersten MJZUMA-7 Investigators; Kite members, Survival with axicabtagene ciloleucelin large B-cell lymphoma: N Engl J Med, 2023; 389(2); 148-57

14. Palomba ML, Ghione P, Patel AR, A 24-month updated analysis of the comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma: Expert Rev Anticancer Ther, 2023; 23(2); 199-206

15. Wang M, Munoz J, Goy A, KTE-X19CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma: N Engl J Med, 2020; 382(14); 1331-42

16. Wang M, Siddiqi T, Gordon LI, Lisocabtagene maraleucel in relapsed/refractory mantle cell lymphoma: primary analysis of the mantle cell lymphoma cohort from TRANSCEND NHL 001, a phase I multicenter seamless design study: J Clin Oncol, 2024; 42(10); 1146-57

17. Lin Y, Raje NS, Berdeja JG, Idecabtagene vicleucel for relapsed and refractory multiple myeloma: Post hoc 18-month follow-up of a phase 1 trial: Nat Med, 2023; 29(9); 2286-94

18. Martin T, Usmani SZ, Berdeja JG, Ciltacabtagene autoleucel, an anti-B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up: J Clin Oncol, 2023; 41(6); 1265-74

19. San-Miguel J, Dhakal B, Yong K, Cilta-cel or standard care in lenalidomide-refractory multiple myeloma: N Engl J Med, 2023; 389(4); 335-47

20. Rodriguez-Otero P, Ailawadhi S, Arnulf B, Ide-cel or standard regimens in relapsed and refractory multiple myeloma: N Engl J Med, 2023; 388(11); 1002-14

21. Xu J, Wang BY, Yu SH, Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial: J Hematol Oncol, 2024; 17(1); 23

22. Ghilardi G, Fraietta JA, Gerson JN, T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy: Nat Med, 2024; 30(4); 984-89

23. Gurney M, Baranwal A, Rosenthal A, Features and factors associated with myeloid neoplasms after chimeric antigen receptor T-cell therapy: JAMA Oncol, 2024; 10(4); 532-35

24. Levine BL, Pasquini MC, Connolly JE, Unanswered questions following reports of secondary malignancies after CAR-T cell therapy: Nat Med, 2024; 30(2); 338-41

25. Plaks V, Rossi JM, Chou J, CD19 target evasion as a mechanism of relapse in large B-cell lymphoma treated with axicabtagene ciloleucel: Blood, 2021; 138(12); 1081-85

26. Fraietta JA, Lacey SF, Orlando EJ, Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia: Nat Med, 2018; 24(5); 563-71

27. Locke FL, Rossi JM, Neelapu SS, Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma: Blood Adv, 2020; 4(19); 4898-911

28. Lee DW, Gardner R, Porter DL, Current concepts in the diagnosis and management of cytokine release syndrome: Blood, 2014; 124(2); 188-95

29. Lee DW, Santomasso BD, Locke FL, ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells: Biol Blood Marrow Transplant, 2019; 25(4); 625-38

30. Maus MV, Alexander S, Bishop MR, Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events: J Immunother Cancer, 2020; 8(2); e001511

31. Santomasso BD, Nastoupil LJ, Adkins S, Management of immune-related adverse events in patients treated with chimeric antigen receptor T-cell therapy: ASCO guideline: J Clin Oncol, 2021; 39(35); 3978-92

32. Hayden PJ, Roddie C, Bader P, 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, 2022; 33(3); 259-75

33. Rejeski K, Subklewe M, Locke FL, Recognizing, defining, and managing CAR-T hematologic toxicities: Hematology Am Soc Hematol Educ Program, 2023; 2023(1); 198-208

34. Bhoj VG, Arhontoulis D, Wertheim G, Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy: Blood, 2016; 128(3); 360-70

35. Hill JA, Seo SK, How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies: Blood, 2020; 136(8); 925-35

36. Barone A, Chiappella A, Casadei B, Secondary primary malignancies after CD-19 directed CAR-T-cell therapy in lymphomas: A report from the Italian CART-SIE study: Br J Haematol, 2024; 205(4); 1356-60

37. Legend Biotech Corporation: Form 6-K: Legend Biotech announces US FDA label update for CARVYKTI (ciltacabtagene autoleucel; cilta-cel), 2024, US Securities and Exchange Commission Available from: https://investors.legendbiotech.com/static-files/e40632fa-bb0c-4a3e-ac55-0ca85b212d76

38. Verdun N, Marks P, Secondary cancers after chimeric antigen receptor T-cell therapy: N Engl J Med, 2024; 390(7); 584-86

39. Schmidts A, Maus MV, Making CAR T cells a solid option for solid tumors: Front Immunol, 2018; 9; 2593

40. Norberg SM, Hinrichs CS, Engineered T cell therapy for viral and non-viral epithelial cancers: Cancer Cell, 2023; 41(1); 58-69

41. Del Bufalo F, De Angelis B, Caruana IPrecision Medicine Team – IRCCS Ospedale Pediatrico Bambino Gesù, GD2-CART01 for relapsed or refractory high-risk neuroblastoma: N Engl J Med, 2023; 388(14); 1284-95

42. Narayan V, Barber-Rotenberg JS, Jung IYProstate Cancer Cellular Therapy Program Investigators, PSMA-targeting TGFβ-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: A phase 1 trial: Nat Med, 2022; 28(4); 724-34

43. Brown CE, Alizadeh D, Starr R, Regression of glioblastoma after chimeric antigen receptor T-cell therapy: N Engl J Med, 2016; 375(26); 2561-69

44. Choi BD, Gerstner ER, Frigault MJ, Intraventricular CARv3-TEAM-E T cells in recurrent glioblastoma: N Engl J Med, 2024; 390(14); 1290-98

45. Parums DV, Editorial: First regulatory approval for adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs) – Lifileucel (Amtagvi): Med Sci Monit, 2024; 30; e944927

46. Food and Drug Administration (FDA): FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma Feb 16, 2024 Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lifileucel-unresectable-or-metastatic-melanoma

47. Warner AB, Hamid O, Komanduri K, Expert consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy: J Immunother Cancer, 2024; 12(2); e008735

48. Kim SP, Vale NR, Zacharakis N, Adoptive cellular therapy with autologous tumor-infiltrating lymphocytes and T-cell receptor-engineered T cells targeting common p53 neoantigens in human solid tumors: Cancer Immunol Res, 2022; 10(8); 932-46

49. Stevanović S, Helman SR, Wunderlich JR, A phase II study of tumor-infiltrating lymphocyte therapy for human papillomavirus-associated epithelial cancers: Clin Cancer Res, 2019; 25(5); 1486-93

50. Jazaeri AA, Zsiros E, Amaria RN, Safety and efficacy of adoptive cell transfer using autologous tumor infiltrating lymphocytes (LN-145) for treatment of recurrent, metastatic, or persistent cervical carcinoma: J Clin Oncol, 2019; 15(Suppl); 2538

51. Baulu E, Gardet C, Chuvin N, Depil S, TCR-engineered T cell therapy in solid tumors: State of the art and perspectives: Sci Adv, 2023; 9(7); eadf3700

52. US Food and Drug Administration, FDA grants accelerated approval to afamitrersgene autoleucel for unresectable or metastatic synovial sarcoma August 2, 2024 Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-afamitresgene-autoleucel-unresectable-or-metastatic-synovial-sarcoma

53. D’Angelo SP, Araujo DM, Abdul Razak AR, Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): An international, open-label, phase 2 trial: Lancet, 2024; 403(10435); 1460-71

54. Doran SL, Stevanović S, Adhikary S, T-cell receptor gene therapy for human papillomavirus-associated epithelial cancers: A first-in-human, phase I/II study: J Clin Oncol, 2019; 37(30); 2759-68

55. Nagarsheth NB, Norberg SM, Sinkoe AL, TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers: Nat Med, 2021; 27(3); 419-25

56. Li T, Niu M, Zhang W, CAR-NK cells for cancer immunotherapy: Recent advances and future directions: Front Immunol, 2024; 15; 1361194

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750