CAR T cell therapy for T cell leukemia and lymphoma: latest updates from 2022 ASH Annual Meeting

Huang, Qiu-Sha; Zhang, Xiao-Hui; Liu, Delong

doi:10.1186/s13045-023-01406-8

Cited by 5 publications

(5 citation statements)

References 8 publications

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“…Lagging behind T cell redirection are those strategies focused on the recruitment of NK cells: NKCE and CAR-NK. Although still preliminary, early reports on CAR-NK cells clinical trials in hematological malignancies suggest a better safety profile than CAR-T cells (neither CRS nor ICANS observed) [149]. Of note, the choice of NK cell source (for example, umbilical cord blood and induced pluripotent stem cells) may allow CAR-NK cells being considered off-the-shelf therapies.…”

Section: T Cell Engagers and Car-t Cells: Where Do We Stand?mentioning

confidence: 99%

Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies

Tapia-Galisteo,

Álvarez-Vallina,

Sanz

2023

J Hematol Oncol

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Immune cell engagers are engineered antibodies with at least one arm binding a tumor-associated antigen and at least another one directed against an activating receptor in immune effector cells: CD3 for recruitment of T cells and CD16a for NK cells. The first T cell engager (the anti-CD19 blinatumomab) was approved by the FDA in 2014, but no other one hit the market until 2022. Now the field is gaining momentum, with three approvals in 2022 and 2023 (as of May): the anti-CD20 × anti-CD3 mosunetuzumab and epcoritamab and the anti-B cell maturation antigen (BCMA) × anti-CD3 teclistamab, and another three molecules in regulatory review. T cell engagers will likely revolutionize the treatment of hematological malignancies in the short term, as they are considerably more potent than conventional monoclonal antibodies recognizing the same tumor antigens. The field is thriving, with a plethora of different formats and targets, and around 100 bispecific T cell engagers more are already in clinical trials. Bispecific NK cell engagers are also in early-stage clinical studies and may offer similar efficacy with milder side effects. Trispecific antibodies (engaging either T cell or NK cell receptors) raise the game even further with a third binding moiety, which allows either the targeting of an additional tumor-associated antigen to increase specificity and avoid immune escape or the targeting of additional costimulatory receptors on the immune cell to improve its effector functions. Altogether, these engineered molecules may change the paradigm of treatment for relapsed or refractory hematological malignancies.

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Section: T Cell Engagers and Car-t Cells: Where Do We Stand?mentioning

confidence: 99%

Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies

Tapia-Galisteo,

Álvarez-Vallina,

Sanz

2023

J Hematol Oncol

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“…This protein is also expressed on NK cells, where it is related to activation and maturation ( 32 ). Fratricide results in reduced anti-tumoral activity, decreased survival of CAR-T cells and limited therapeutic success ( 33 ). Approaches to reduce fratricide include nanobody-based techniques ( 34 , 35 ), natural selection of fratricide-resistant CAR-T cells ( 36 , 37 ), and the use of antibodies ( 38 ) or protein expression blockers ( 39 ).…”

Section: T-cell Malignanciesmentioning

confidence: 99%

Broadening the horizon: potential applications of CAR-T cells beyond current indications

Karsten,

Matrisch,

Cichutek

et al. 2023

Front. Immunol.

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Engineering immune cells to treat hematological malignancies has been a major focus of research since the first resounding successes of CAR-T-cell therapies in B-ALL. Several diseases can now be treated in highly therapy-refractory or relapsed conditions. Currently, a number of CD19- or BCMA-specific CAR-T-cell therapies are approved for acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), multiple myeloma (MM), and follicular lymphoma (FL). The implementation of these therapies has significantly improved patient outcome and survival even in cases with previously very poor prognosis. In this comprehensive review, we present the current state of research, recent innovations, and the applications of CAR-T-cell therapy in a selected group of hematologic malignancies. We focus on B- and T-cell malignancies, including the entities of cutaneous and peripheral T-cell lymphoma (T-ALL, PTCL, CTCL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), classical Hodgkin-Lymphoma (HL), Burkitt-Lymphoma (BL), hairy cell leukemia (HCL), and Waldenström’s macroglobulinemia (WM). While these diseases are highly heterogenous, we highlight several similarly used approaches (combination with established therapeutics, target depletion on healthy cells), targets used in multiple diseases (CD30, CD38, TRBC1/2), and unique features that require individualized approaches. Furthermore, we focus on current limitations of CAR-T-cell therapy in individual diseases and entities such as immunocompromising tumor microenvironment (TME), risk of on-target-off-tumor effects, and differences in the occurrence of adverse events. Finally, we present an outlook into novel innovations in CAR-T-cell engineering like the use of artificial intelligence and the future role of CAR-T cells in therapy regimens in everyday clinical practice.

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“…Alyssa achieved remission and underwent a bone marrow transplant to restore her immune system. Six months after treatment, her condition had significantly improved, and her cancer cells were undetectable [18,43]. On December 2, 2022, the FDA approved Beam Therapeutics' base editing-based CAR-T cell therapy, BEAM-201, for use in a clinical trial addressing relapsed/ refractory acute T-lymphoblastic leukemia (R/R T-ALL) and T-lymphoblastic lymphoma.…”

Section: Reviewmentioning

confidence: 99%

Base editing therapy forges ahead

Jiang¹

2023

Hematology and Oncology Discovery

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CRISPR/Cas-based gene editing is an innovative biotechnology that has revolutionized genetic engineering in recent years. The process involves induction of a double-strand break (DSB) at the desired DNA site and subsequent cellular repair. Two primary mechanisms drive DSB repair: non-homologous end joining and homologous recombination-mediated repair. Non-homologous end joining, the primary mode of DSB repair, is a simple high-efficiency process that is susceptible to errors, and unpredictable nucleotide insertion or deletion mutations. In contrast, point mutations account for more than 50% of human genetic disorders and are the most frequent type of genetic variation in nature. Base editing is a precise gene editing approach in which a single DNA base is substituted without introduction of DSBs or use of a repair template. This technique has promising therapeutic potential in gene therapy, owing to its high efficiency and controllable editing results. Since the invention of the first base editing tools, the technique has rapidly developed and undergone clinical trials. This review summarizes progress in gene therapy through base editing, including DNA and RNA base editing, with particular emphasis on recent clinical trial and preclinical research advancements, current limitations and remaining challenges, and prospects for further research and applications.

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CAR T cell therapy for T cell leukemia and lymphoma: latest updates from 2022 ASH Annual Meeting

Cited by 5 publications

References 8 publications

Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies

Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies

Broadening the horizon: potential applications of CAR-T cells beyond current indications

Base editing therapy forges ahead

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