Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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CAR-Based Cell and Gene Therapies: Global Clinical Landscape and Emerging Therapeutic Strategies from ClinicalTrials.gov

  • Saerom Moon (College of Pharmacy, Duksung Women's University) ;
  • Kyoung Song (College of Pharmacy, Duksung Women's University)
  • Received : 2025.08.12
  • Accepted : 2025.09.30
  • Published : 2025.11.01
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Abstract

Chimeric Antigen Receptor (CAR)-based cell and gene therapies have become transformative treatments, offering targeted and durable responses, especially in hematologic malignancies. This review analyzes 1,744 CAR clinical trials registered on Clinical-Trials.gov as of 2024, focusing on platform types, indications, target antigens, therapeutic strategies, and late-phase development. CAR-T therapies predominate, followed by CAR-NK, CAR-NKT, CAR-M and CAR-DC platforms. Approximately 92% of trials target tumors, with hematologic malignancies accounting for 65% of indications; CD19 and BCMA are primary targets in Phase 3 studies. Solid tumor applications are expanding steadily, driven by unmet clinical needs and advances in CAR engineering. Although monospecific CARs dominate, dual, bispecific, and universal designs are gaining traction to overcome antigen heterogeneity and tumor escape. Combination therapies, such as CAR-T with chemotherapy or monoclonal antibodies, are increasingly used to improve efficacy. CAR-NK therapies, while in early development, show promise due to favorable safety profiles and off-the-shelf allogeneic potential. The United States and China lead global development, supported by robust research ecosystems and industrial investment. Overall, CAR-based therapeutics are evolving from hematologic specialization toward broader clinical application, addressing challenges and guiding future strategies.

Keywords

Acknowledgement

This research was supported by Duksung Women's University Research Grants 2023-3000009004.

References

  1. Badar, T. and Shah, N. N. (2020) Chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia. Curr. Treat. Options Oncol. 21, 16.
  2. Billadeau, D. D., Upshaw, J. L., Schoon, R. A., Dick, C. J. and Leibson, P. J. (2003) NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway. Nat. Immunol. 4, 557-564. https://doi.org/10.1038/ni929
  3. BLOOMBERG (2019) Bristol-Myers Squibb buying Celgene in $74 billion deal. In St. Louis Post-Dispatch, B4.
  4. Cao, L., Zhao, Y., Chen, Y., Ma, P., Xie, J., Pan, X., Zhang, X., Chen, Y., Wang, Q. and Xie, L. (2025) CAR-T cell therapy clinical trials: global progress, challenges, and future directions from ClinicalTrials.gov insights. Front. Immunol. 16, 1583116. https://doi.org/10.3389/fimmu.2025.1583116
  5. Cho, J., Tae, N., Ahn, J., Chang, S., Ko, H. and Kim, D. H. (2022) Bispecific antibody-bound T cells as a novel anticancer immunotherapy. Biomol. Ther. (Seoul) 30, 418-426. https://doi.org/10.4062/biomolther.2022.015
  6. Choi, G., Shin, G. and Bae, S. (2022) Price and prejudice? The value of chimeric antigen receptor (CAR) T-cell therapy. Int. J. Environ. Res. Public Health 19, 12366.
  7. Dagher, O. K. and Posey, A. D. (2023) Forks in the road for CAR T and CAR NK cell cancer therapies. Nat. Immunol. 24, 1994-2007. https://doi.org/10.1038/s41590-023-01659-y
  8. Daher, M. and Rezvani, K. (2021) Outlook for new CAR-based therapies with a focus on CAR NK cells: what lies beyond CAR-engineered T cells in the race against cancer. Cancer Discov. 11, 45-58. https://doi.org/10.1158/2159-8290.CD-20-0556
  9. Davies, J. O. J., Stringaris, K., Barrett, A. J. and Rezvani, K. (2014) Opportunities and limitations of natural killer cells as adoptive therapy for malignant disease. Cytotherapy (Oxford, England) 16, 1453-1466. https://doi.org/10.1016/j.jcyt.2014.03.009
  10. dos Reis, F. D., Saidani, Y., Martín-Rubio, P., Sanz-Pamplona, R., Stojanovic, A. and Correia, M. P. (2025) CAR-NK cells: harnessing the power of natural killers for advanced cancer therapy. Front. Immunol. 16, 1603757.
  11. Du, X., Luo, X., Liu, L., Cao, Y., Zhang, Y. and Zhang, Y. (2024) Mapping the cell therapy landscape: insights into clinical trials and regulatory advances in China. J. Hematol. Oncol. 17, 96. https://doi.org/10.1186/s13045-024-01616-8
  12. Fan, M., Li, M., Gao, L., Geng, S., Wang, J., Wang, Y., Yan, Z. and Yu, L. (2017) Chimeric antigen receptors for adoptive T cell therapy in acute myeloid leukemia. J. Hematol. Oncol. 10, 151.
  13. Fiorenza, S., Ritchie, D. S., Ramsey, S. D., Turtle, C. J. and Roth, J. A. (2020) Value and affordability of CAR T-cell therapy in the United States. Bone Marrow Transplant. 55, 1706-1715. https://doi.org/10.1038/s41409-020-0956-8
  14. Gale, R. P. (2022) Chimeric antigen receptor-T-cell therapy: China leading the way. Blood Sci. 4, 176. https://doi.org/10.1097/BS9.0000000000000118
  15. Garfall, A. L., Lancaster, E., Stadtmauer, E. A., Lacey, S. F., Dengel, K., Ambrose, D. E., Chen, F., Gupta, M., Kulikovskaya, I., Vogl, D. T., Plesa, G., Weiss, B. M., Ferthio, R., Richardson, C., Melenhorst, J. J., Levine, B. L., June, C. H., Milone, M. and Cohen, A. D. (2016) Posterior reversible encephalopathy syndrome (PRES) after infusion of anti-Bcma CAR T cells (CART-BCMA) for multiple myeloma: successful treatment with cyclophosphamide. Blood 128, 5702. https://doi.org/10.1182/blood.V128.22.5702.5702
  16. Giorgioni, L., Ambrosone, A., Cometa, M. F., Salvati, A. L. and Magrelli, A. (2023) CAR-T state of the art and future challenges, a regulatory perspective. Int. J. Mol. Sci. 24, 11803.
  17. Giorgioni, L., Ambrosone, A., Cometa, M. F., Salvati, A. L., Nisticò, R. and Magrelli, A. (2024) Revolutionizing CAR T-Cell therapies: innovations in genetic engineering and manufacturing to enhance efficacy and accessibility. Int. J. Mol. Sci. 25, 10365.
  18. Hadiloo, K., Tahmasebi, S. and Esmaeilzadeh, A. (2023) CAR-NKT cell therapy: a new promising paradigm of cancer immunotherapy. Cancer Cell Int. 23, 86-22. https://doi.org/10.1186/s12935-023-02923-9
  19. Honikel, M. M. and Olejniczak, S. H. (2022) Co-stimulatory receptor signaling in CAR-T cells. Biomolecules (Basel, Switzerland) 12, 1303. https://doi.org/10.3390/biom12091303
  20. Hu, Y., Feng, J., Gu, T., Wang, L., Wang, Y., Zhou, L., Hong, R., Tan Su Yin, E., Zhang, M., Lu, P. and Huang, H. (2022) CAR T-cell therapies in China: rapid evolution and a bright future. Lancet Haematol. 9, e930-e941. https://doi.org/10.1016/S2352-3026(22)00291-5
  21. Imai, C., Iwamoto, S. and Campana, D. (2005) Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood 106, 376-383. https://doi.org/10.1182/blood-2004-12-4797
  22. Iyer, R. K., Bowles, P. A., Kim, H. and Dulgar-Tulloch, A. (2018) Industrializing autologous adoptive immunotherapies: manufacturing advances and challenges. Front. Med. 5, 150.
  23. Jensen, M. C. and Riddell, S. R. (2014) Design and implementation of adoptive therapy with chimeric antigen receptor-modified T cells. Immunol. Rev. 257, 127-144. https://doi.org/10.1111/imr.2013.257.issue-1
  24. Jørgensen, L. V., Christensen, E. B., Barnkob, M. B. and Barington, T. (2025) The clinical landscape of CAR NK cells. Exp. Hematol. Oncol. 14, 46.
  25. Kriegsmann, K., Kriegsmann, M., von Bergwelt-Baildon, M., Cremer, M. and Witzens-Harig, M. (2018) NKT cells — New players in CAR cell immunotherapy? Eur. J. Haematol. 101, 750-757. https://doi.org/10.1111/ejh.2018.101.issue-6
  26. Kruschinski, A., Moosmann, A., Poschke, I., Norell, H., Chmielewski, M., Seliger, B., Kiessling, R., Blankenstein, T., Abken, H. and Charo, J. (2008) Engineering antigen-specific primary human NK cells against HER-2 positive carcinomas. Proc. Natl. Acad. Sci. U. S. A. 105, 17481-17486. https://doi.org/10.1073/pnas.0804788105
  27. Lanier, L. L., Corliss, B. C., Wu, J., Leong, C. and Phillips, J. H. (1998) Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature 391, 703-707. https://doi.org/10.1038/35642
  28. Li, J., Hu, H., Lian, H., Yang, S., Liu, M., He, J., Cao, B., Chen, D., Hu, Y., Zhi, C., Shen, Y., Ye, X., He, B., Zhao, M., Fan, W., Xu, L., Leidner, R., Wu, Q., Yang, L. and Zhang, Z. (2024) NK-92MI cells engineered with anti-claudin-6 chimeric antigen receptors in immunotherapy for ovarian cancer. Int. J. Biol. Sci. 20, 1578-1601. https://doi.org/10.7150/ijbs.88539
  29. Li, Y., Zhou, Y., Yu, J., Zhu, Y., Lee, D., Zhu, E., Li, Z., Kim, Y. J., Zhou, K., Fang, Y., Lyu, Z., Chen, Y., Tian, Y., Huang, J., Cen, X., Husman, T., Cho, J. M., Hsiai, T., Zhou, J. J., Wang, P., Puliafito, B. R., Larson, S. M. and Yang, L. (2024) Engineering allorejection-resistant CAR-NKT cells from hematopoietic stem cells for off-the-shelf cancer immunotherapy. Mol. Ther. 32, 1849-1874. https://doi.org/10.1016/j.ymthe.2024.04.005
  30. Li, Y., Hermanson, D. L., Moriarity, B. S. and Kaufman, D. S. (2018) Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity. Cell Stem Cell 23, 181-192.e5. https://doi.org/10.1016/j.stem.2018.06.002
  31. Litvinova, Y., Merkur, S., Allin, S., Angulo-Pueyo, E., Behmane, D., Bernal-Delgado, E., Dalmas, M., De Belvis, A., Edwards, N., Estupiñán-Romero, F., Gaal, P., Gerkens, S., Jamieson, M., Morsella, A., Picecchi, D., Røshol, H., Saunes, I. S., Sullivan, T., Szécsényi-Nagy, B., Vijver, I. V. D., Walter, R. and Panteli, D. (2024) Availability and financing of CAR-T cell therapies: a cross-country comparative analysis. Health Policy (Amsterdam) 149, 105153. https://doi.org/10.1016/j.healthpol.2024.105153
  32. Liu, E., Marin, D., Banerjee, P., Macapinlac, H. A., Thompson, P., Basar, R., Nassif Kerbauy, L., Overman, B., Thall, P., Kaplan, M., Nandivada, V., Kaur, I., Nunez Cortes, A., Cao, K., Daher, M., Hosing, C., Cohen, E. N., Kebriaei, P., Mehta, R., Neelapu, S., Nieto, Y., Wang, M., Wierda, W., Keating, M., Champlin, R., Shpall, E. J. and Rezvani, K. (2020) Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N. Engl. J. Med. 382, 545-553. https://doi.org/10.1056/NEJMoa1910607
  33. Locke, F. L., Ghobadi, A., Jacobson, C. A., Miklos, D. B., Lekakis, L. J., Oluwole, O. O., Lin, Y., Braunschweig, I., Hill, B. T., Timmerman, J. M., Deol, A., Reagan, P. M., Stiff, P., Flinn, I. W., Farooq, U., Goy, A., McSweeney, P. A., Munoz, J., Siddiqi, T., Chavez, J. C., Herrera, A. F., Bartlett, N. L., Wiezorek, J. S., Navale, L., Xue, A., Jiang, Y., Bot, A., Rossi, J. M., Kim, J. J., Go, W. Y. and Neelapu, S. S. (2019) Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 20, 31-42. https://doi.org/10.1016/S1470-2045(18)30864-7
  34. Lyman, G. H., Nguyen, A., Snyder, S., Gitlin, M. and Chung, K. C. (2020) Economic evaluation of chimeric antigen receptor T-cell therapy by site of care among patients with relapsed or refractory large B-cell lymphoma. JAMA Netw. Open 3, e202072. https://doi.org/10.1001/jamanetworkopen.2020.2072
  35. Majzner, R. G. and Mackall, C. L. (2019) Clinical lessons learned from the first leg of the CAR T cell journey. Nat. Med. 25, 1341-1355. https://doi.org/10.1038/s41591-019-0564-6
  36. Mansoori, S., Noei, A., Maali, A., Seyed-Motahari, S. S. and Sharifzadeh, Z. (2024) Recent updates on allogeneic CAR-T cells in hematological malignancies. Cancer Cell Int. 24, 304. https://doi.org/10.1186/s12935-024-03479-y
  37. Mariz, S., Reese, J. H., Westermark, K., Greene, L., Goto, T., Hoshino, T., Llinares-garcia, J. and Sepodes, B. (2016) Worldwide collaboration for orphan drug designation. Nat. Rev. Drug Discov. 15, 588. https://doi.org/10.1038/nrd.2016.143
  38. Marofi, F., Saleh, M. M., Rahman, H. S., Suksatan, W., Al-Gazally, M. E., Abdelbasset, W. K., Thangavelu, L., Yumashev, A. V., Hassanzadeh, A., Yazdanifar, M., Motavalli, R., Pathak, Y., Naimi, A., Baradaran, B., Nikoo, M. and Khiavi, F. M. (2021) CAR-engineered NK cells; a promising therapeutic option for treatment of hematological malignancies. Stem Cell Res. Ther. 12, 374.
  39. Maude, S. L., Frey, N., Shaw, P. A., Aplenc, R., Barrett, D. M., Bunin, N. J., Chew, A., Gonzalez, V. E., Zheng, Z., Lacey, S. F., Mahnke, Y. D., Melenhorst, J. J., Rheingold, S. R., Shen, A., Teachey, D. T., Levine, B. L., June, C. H., Porter, D. L. and Grupp, S. A. (2014) Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 371, 1507-1517. https://doi.org/10.1056/NEJMoa1407222
  40. Maude, S. L., Laetsch, T. W., Buechner, J., Rives, S., Boyer, M., Bittencourt, H., Bader, P., Verneris, M. R., Stefanski, H. E., Myers, G. D., Qayed, M., De Moerloose, B., Hiramatsu, H., Schlis, K., Davis, K. L., Martin, P. L., Nemecek, E. R., Yanik, G. A., Peters, C., Baruchel, A., Boissel, N., Mechinaud, F., Balduzzi, A., Krueger, J., June, C. H., Levine, B. L., Wood, P., Taran, T., Leung, M., Mueller, K. T., Zhang, Y., Sen, K., Lebwohl, D., Pulsipher, M. A. and Grupp, S. A. (2018) Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N. Engl. J. Med. 378, 439-448. https://doi.org/10.1056/NEJMoa1709866
  41. Mhaidly, R. and Verhoeyen, E. (2020) Humanized mice are precious tools for preclinical evaluation of CAR T and CAR NK cell therapies. Cancers 12, 1915. https://doi.org/10.3390/cancers12071915
  42. Mitra, A., Barua, A., Huang, L., Ganguly, S., Feng, Q. and He, B. (2023) From bench to bedside: the history and progress of CAR T cell therapy. Front. Immunol. 14, 1188049. https://doi.org/10.3389/fimmu.2023.1188049
  43. Morris, E. C., Neelapu, S. S., Giavridis, T. and Sadelain, M. (2022) Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat. Rev. Immunol. 22, 85-96. https://doi.org/10.1038/s41577-021-00547-6
  44. Morva, A., Arroyo, A. B., Andreeva, L., Tapia-Abellán, A. and Luengo-Gil, G. (2025) Unleashing the power of CAR-M therapy in solid tumors: a comprehensive review. Front. Immunol. 16, 1615760. https://doi.org/10.3389/fimmu.2025.1615760
  45. Moses, H., Matheson, D. H. M., Cairns-Smith, S., George, B. P., Palisch, C. and Dorsey, E. R. (2015) The anatomy of medical research: US and international comparisons. JAMA 313, 174-189. https://doi.org/10.1001/jama.2014.15939
  46. Mullin, R. (2017) Gilead to acquire Kite Pharma for $11.9 billion. C&EN Global Enterp. 95, 15. https://doi.org/10.1021/cen-09535-notw12
  47. Na, Y. R., Kim, S. W. and Seok, S. H. (2023) A new era of macrophage-based cell therapy. Exp. Mol. Med. 55, 1945-1954. https://doi.org/10.1038/s12276-023-01068-z
  48. Nakajima, H. and Colonna, M. (2000) 2B4: an NK cell activating receptor with unique specificity and signal transduction mechanism. Human Immunol. 61, 39-43. https://doi.org/10.1016/S0198-8859(99)00170-6
  49. Packalen, M. and Bhattacharya, J. (2020) NIH funding and the pursuit of edge science. Proc. Natl. Acad. Sci. U. S. A. 117, 12011-12016. https://doi.org/10.1073/pnas.1910160117
  50. Pan, K., Farrukh, H., Chittepu, V. C. S. R., Xu, H., Pan, C. and Zhu, Z. (2022) CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy. J. Exp. Clin. Cancer Res. 41, 119. https://doi.org/10.1186/s13046-022-02327-z
  51. Paul, S. and Lal, G. (2017) The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy. Front. Immunol. 8, 1124.
  52. Peng, L., Sferruzza, G., Yang, L., Zhou, L. and Chen, S. (2024) CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors. Cell. Mol. Immunol. 21, 1089-1108. https://doi.org/10.1038/s41423-024-01207-0
  53. Perez, C. R. and De Palma, M. (2019) Engineering dendritic cell vaccines to improve cancer immunotherapy. Nat. Commun. 10, 5408.
  54. Priesner, C. and Hildebrandt, M. (2022) Advanced therapy medicinal products and the changing role of academia. Transfus. Med. Hemother. 49, 158-162. https://doi.org/10.1159/000524392
  55. Rafiq, S., Hackett, C. S. and Brentjens, R. J. (2020) Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nat. Rev. Clin. Oncol. 17, 147-167. https://doi.org/10.1038/s41571-019-0297-y
  56. Rezvani, K., Rouce, R., Liu, E. and Shpall, E. (2017) Engineering natural killer cells for cancer immunotherapy. Mol. Ther. 25, 1769-1781. https://doi.org/10.1016/j.ymthe.2017.06.012
  57. Rodriguez-Cartagena, L. G., Bowles, B. S., Kurani, S. S., Windebank, A. J., Kenderian, S. S. and Greenberg-Worisek, A. J. (2018) Chimeric antigen receptor T-cells: successful translation of the first cell and gene therapy from bench to bedside. Clin. Transl. Sci. 11, 537-539. https://doi.org/10.1111/cts.v11.6
  58. Schuster, S. J., Bishop, M. R., Tam, C. S., Waller, E. K., Borchmann, P., McGuirk, J. P., Jäger, U., Jaglowski, S., Andreadis, C., Westin, J. R., Fleury, I., Bachanova, V., Foley, S. R., Ho, P. J., Mielke, S., Magenau, J. M., Holte, H., Pantano, S., Pacaud, L. B., Awasthi, R., Chu, J., Anak, Ö, Salles, G. and Maziarz, R. T. (2019) Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N. Engl. J. Med. 380, 45-56. https://doi.org/10.1056/NEJMoa1804980
  59. Selker, H. P. and Califf, R. M. (2011) The need for academic leadership in full-spectrum translational research. Clin. Transl. Sci. 4, 78-79. https://doi.org/10.1111/cts.2011.4.issue-2
  60. Sheth, V. S. and Gauthier, J. (2021) Taming the beast: CRS and ICANS after CAR T-cell therapy for ALL. Bone Marrow Transplant. 56, 552-566. https://doi.org/10.1038/s41409-020-01134-4
  61. Shin, M. H., Oh, E., Kim, Y., Nam, D., Jeon, S. Y., Yu, J. H. and Minn, D. (2023) Recent advances in CAR-based solid tumor immunotherapy. Cells 12, 1606. https://doi.org/10.3390/cells12121606
  62. Tangye, S. G., Cherwinski, H., Lanier, L. L. and Phillips, J. H. (2000) 2B4-mediated activation of human natural killer cells. Mol. Immunol. 37, 493-501. https://doi.org/10.1016/S0161-5890(00)00076-6
  63. Töpfer, K., Cartellieri, M., Michen, S., Wiedemuth, R., Müller, N., Lindemann, D., Bachmann, M., Füssel, M., Schackert, G. and Temme, A. (2015) DAP12-based activating chimeric antigen receptor for NK cell tumor immunotherapy. J. Immunol. 194, 3201-3212. https://doi.org/10.4049/jimmunol.1400330
  64. Wang, Z. (2024) Challenges and feasible solutions of CART therapy in solid tumors. MedScien 1. doi: 10.61173/db2q9t74.
  65. Wei, J., Guo, Y., Wang, Y., Wu, Z., Bo, J., Zhang, B., Zhu, J. and Han, W. (2021) Clinical development of CAR T cell therapy in China: 2020 update. Cell. Mol. Immunol. 18, 792-804. https://doi.org/10.1038/s41423-020-00555-x
  66. Wei, J., Yang, Y., Wang, G. and Liu, M. (2022) Current landscape and future directions of bispecific antibodies in cancer immunotherapy. Front. Immunol. 13, 1035276.
  67. Wu, W., Wang, Y., Tang, Z., Gao, Y. and Huo, Y. (2020) Regulatory oversight of cell therapy in China: government's efforts in patient access and therapeutic innovation. Pharmacol. Res. 158, 104889. https://doi.org/10.1016/j.phrs.2020.104889
  68. Wu, X. and Matosevic, S. (2022) Gene-edited and CAR-NK cells: opportunities and challenges with engineering of NK cells for immunotherapy. Mol. Ther. Oncolytics 27, 224-238. https://doi.org/10.1016/j.omto.2022.10.011
  69. Xu, Y., Liu, Q., Zhong, M., Wang, Z., Chen, Z., Zhang, Y., Xing, H., Tian, Z., Tang, K., Liao, X., Rao, Q., Wang, M. and Wang, J. (2019) 2B4 costimulatory domain enhancing cytotoxic ability of anti-CD5 chimeric antigen receptor engineered natural killer cells against T cell malignancies. J. Hematol. Oncol. 12, 49. https://doi.org/10.1186/s13045-019-0732-7
  70. Yang, J., Hu, S., Shangguan, J., Eresen, A., Li, Y., Pan, L., Ma, Q., Velichko, Y., Wang, J., Hu, C., Yaghmai, V. and Zhang, Z. (2019) Dendritic cell immunotherapy induces anti-tumor effect in a transgenic mouse model of pancreatic ductal adenocarcinoma. Am. J. Cancer Res. 9, 2456-2468
  71. Yin, C., Gao, J., Li, G., Hu, H., Zhou, L., Lu, S. and Chen, X. (2022) Gene and cell therapies in China: booming landscape under dual track regulation. J. Hematol. Oncol. 15, 139. https://doi.org/10.1186/s13045-022-01354-9
  72. Zhang, L., Meng, Y., Feng, X. and Han, Z. (2022a) CAR-NK cells for cancer immunotherapy: from bench to bedside. Biomarker Res. 10, 12-19. https://doi.org/10.1186/s40364-022-00364-6
  73. Zhang, P., Zhang, G. and Wan, X. (2023) Challenges and new technologies in adoptive cell therapy. J. Hematol. Oncol. 16, 97.
  74. Zhang, X., Zhu, L., Zhang, H., Chen, S. and Xiao, Y. (2022b) CAR-T cell therapy in hematological malignancies: current opportunities and challenges. Front. Immunol. 13, 927153. https://doi.org/10.3389/fimmu.2022.927153
  75. Zhong, Y. and Liu, J. (2024) Emerging roles of CAR-NK cell therapies in tumor immunotherapy: current status and future directions. Cell Death Discov. 10, 318-319. https://doi.org/10.1038/s41420-024-02077-1
  76. Zhu, X., Xue, J., Jiang, H. and Xue, D. (2024) CAR-NK cells for gastrointestinal cancer immunotherapy: from bench to bedside. Mol. Cancer 23, 237-216.