Recent advances in cellular immunotherapy for lymphoid malignancies

Haerim Chung; Hyunsoo Cho

doi:10.5045/br.2023.2023177

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Blood Res 2023; 58(4):

Published online December 31, 2023

https://doi.org/10.5045/br.2023.2023177

Recent advances in cellular immunotherapy for lymphoid malignancies

Haerim Chung, Hyunsoo Cho

Author Info. +

Division of Hematology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

Correspondence to : Hyunsoo Cho, M.D., Ph.D.
Division of Hematology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
E-mail: hyunsoocho@yuhs.ac

*This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (RS-2023-00208390) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Korea (HI22C1217 and HI22C1826).

Received: September 21, 2023; Revised: October 27, 2023; Accepted: November 1, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Abstract

Cellular immunotherapy with chimeric antigen receptor (CAR) T-cells has revolutionized the treatment of lymphoid malignancies. This review addresses the need for CAR expression in our endogenous T-cells to kill tumor cells with a focus on the basic principles of T-cell receptor recognition of major histocompatibility complex-peptide complexes. We review the factors associated with CAR T-cell outcomes and recent efforts to employ CAR T-cells in earlier lines of therapy. We also discuss the value of bispecific T-cell engagers as off-the-shelf products with better toxicity profiles. Finally, natural killer cells are discussed as an important cellular immunotherapy platform with the potential to broaden immunotherapeutic applications beyond lymphoid malignancies.

Keywords Cellular immunotherapy, Chimeric antigen receptor T cells, Lymphoma, Multiple myeloma

Article

Review Article

Blood Res 2023; 58(4): 166-172

Published online December 31, 2023 https://doi.org/10.5045/br.2023.2023177

Recent advances in cellular immunotherapy for lymphoid malignancies

Haerim Chung, Hyunsoo Cho

Division of Hematology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

Correspondence to:Hyunsoo Cho, M.D., Ph.D.
Division of Hematology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
E-mail: hyunsoocho@yuhs.ac

*This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (RS-2023-00208390) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Korea (HI22C1217 and HI22C1826).

Received: September 21, 2023; Revised: October 27, 2023; Accepted: November 1, 2023

Abstract

Keywords: Cellular immunotherapy, Chimeric antigen receptor T cells, Lymphoma, Multiple myeloma

Abstract

Table 1 . FDA approved CAR T cells for lymphoid malignancies as of Sep 2023..

Target	Generic name	Trade name (manufacturer)	FDA approval	Indications
CD19	Tisagenlecleucel	Kymriah (Norvatis)	2017 2018 2022	Relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) (third line). R/R large B-cell lymphoma (LBCL) (third line). R/R follicular lymphoma (FL) (third line).
	Brexucabtagene autoleucel	Tecartus (Kite Pharma)	2020 2021	R/R mantle cell lymphoma. R/R B-ALL.
	Axicabtagene ciloleucel	Yescarta (Kite Pharma)	2017 2021 2022	R/R LBCL (third line). R/R FL (third line). R/R LBCL (second line).
	Lisocabtagene maraleucel	Breyanzi (Juno Therapeutics, Bristol-Myers Squibb)	2021 2022	R/R LBCL (third line). R/R LBCL (second line).
BCMA	Idecabtagene vicleucel	Abecma (Celgene, Bristol-Myers Squibb)	2021	R/R multiple myeloma (fifth line).
BCMA	Ciltacabtagene autoleucel	Carvykti (Janssen Biotech)	2022	R/R multiple myeloma (fifth line).

Table 2 . FDA approved bispecific T-cell engager for lymphoid malignancies as of Sep 2023..

Target	Generic name	Trade name (manufacturer)	FDA approval	Indications
CD19×CD3	Blinatumomab	Blincyto (Amgen)	2014 2017 2018	Philadelphia chromosome (Ph)-negative relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (ALL). Ph-positive R/R B-ALL. CD19-positive B-ALL in first or second complete remission with minimal residual disease of at least 0.1%.
BCMA×CD3	Teclistamab-cqyv	Tecvayli (Janssen Biotech)	2022	R/R multiple myeloma (MM) (fifth line).
BCMA×CD3	Elranatamab-bcmm	Elrexfio (Pfizer)	2023	R/R multiple myeloma (MM) (fifth line).
CD20×CD3	Mosunetuzumab-axgb	Lunsumio (Genentech-Roche)	2022	R/R follicular lymphoma (FL) (third line).
	Epcoritamab-bysp	Epkinly (Genmab-AbbVie)	2023	R/R diffuse large B cell lymphoma (DLBCL), high-grade B cell lymphoma (third line).
	Glofitamab-gxbm	Columvi (Genentech-Roche)	2023	R/R DLBCL, large B cell lymphoma arising from FL (third line).
GPRC5D×CD3	Talquetamab-tgvs	Talvey (Janssen Biotech)	2023	R/R MM (fifth line).