An “off-the-shelf” CD2 universal CAR-T therapy for T-cell malignancies

Xiang, Jingyu; Devenport, Jessica M.; Carter, Alun J.; Staser, Karl W.; Kim, Miriam Y.; O’ Neal, Julie; Ritchey, Julie K.; Rettig, Michael P.; Gao, Feng; Rettig, Garrett; Turk, Rolf; Lee, Byung Ha; Cooper, Matthew L.; DiPersio, John F.

doi:10.1038/s41375-023-02039-z

Cited by 14 publications

(9 citation statements)

References 40 publications

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“…These studies underscore the importance of CTCL heterogeneity and highlight the therapeutic potential of coordinated treatments ( Netchiporouk et al, 2017 ; Gallardo et al, 2018 ; Zhang et al, 2018 ; Froehlich et al, 2019 ; Wang et al, 2020 ; Poglio et al, 2021 ; Wu et al, 2021 ). Recent advancements include the superior performance of CCR4-IL2 immunotoxin ( Wang et al, 2023 ), RT39 peptide therapy ( Habault et al, 2022 ), novel drug NT1721 ( Lin et al, 2021 ), JAK3-INSL3 fusion transcripts ( Velatooru et al, 2023 ), anti-CCR4 CAR T cells ( Watanabe et al, 2023 ), universal CD2 CAR-T therapy ( Xiang et al, 2023 ) and the antibody-drug conjugate SGN-CD70A ( Wu et al, 2022 ) have further expanded the therapeutic research landscape for CTCL.…”

Section: Transplantation Mouse Models In Ctcl Researchmentioning

confidence: 99%

“Next top” mouse models advancing CTCL research

Luo,

de Gruijl,

Vermeer

et al. 2024

Front. Cell Dev. Biol.

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This review systematically describes the application of in vivo mouse models in studying cutaneous T-cell lymphoma (CTCL), a complex hematological neoplasm. It highlights the diverse research approaches essential for understanding CTCL’s intricate pathogenesis and evaluating potential treatments. The review categorizes various mouse models, including xenograft, syngeneic transplantation, and genetically engineered mouse models (GEMMs), emphasizing their contributions to understanding tumor-host interactions, gene functions, and studies on drug efficacy in CTCL. It acknowledges the limitations of these models, particularly in fully replicating human immune responses and early stages of CTCL. The review also highlights novel developments focusing on the potential of skin-targeted GEMMs in studying natural skin lymphoma progression and interactions with the immune system from onset. In conclusion, a balanced understanding of these models’ strengths and weaknesses are essential for accelerating the deciphering of CTCL pathogenesis and developing treatment methods. The GEMMs engineered to target specifically skin-homing CD4+ T cells can be the next top mouse models that pave the way for exploring the effects of CTCL-related genes.

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Section: Transplantation Mouse Models In Ctcl Researchmentioning

confidence: 99%

“Next top” mouse models advancing CTCL research

Luo,

de Gruijl,

Vermeer

et al. 2024

Front. Cell Dev. Biol.

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“…However, the clinical application of this approach needs further exploration. Furthermore, gene deletion might diminish the effectiveness of CAR T cells ( 219 , 220 ). There are also safety concerns associated with CRISPR-based gene editing ( 227 ).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

CAR products from novel sources: a new avenue for the breakthrough in cancer immunotherapy

Huang,

Yang,

Wang

et al. 2024

Front. Immunol.

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Chimeric antigen receptor (CAR) T cell therapy has transformed cancer immunotherapy. However, significant challenges limit its application beyond B cell-driven malignancies, including limited clinical efficacy, high toxicity, and complex autologous cell product manufacturing. Despite efforts to improve CAR T cell therapy outcomes, there is a growing interest in utilizing alternative immune cells to develop CAR cells. These immune cells offer several advantages, such as major histocompatibility complex (MHC)-independent function, tumor microenvironment (TME) modulation, and increased tissue infiltration capabilities. Currently, CAR products from various T cell subtypes, innate immune cells, hematopoietic progenitor cells, and even exosomes are being explored. These CAR products often show enhanced antitumor efficacy, diminished toxicity, and superior tumor penetration. With these benefits in mind, numerous clinical trials are underway to access the potential of these innovative CAR cells. This review aims to thoroughly examine the advantages, challenges, and existing insights on these new CAR products in cancer treatment.

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“…To circumvent CD7-related fratricide, researchers are also focusing on finding more suitable biological markers to differentiate between malignant, healthy, and therapeutic T cells. Recent studies have investigated the T-cell receptor β-chain constant domains TRBC1 and TRBC2 ( 24 , 59 ), CD1a ( 60 ), CD2 ( 61 ), CD4 ( 62 ), CD5 ( 63 , 64 ), CD21 ( 65 ), CD26 ( 66 ), CD38 ( 67 ), CD99 ( 68 , 69 ), CCR9 ( 70 ), the natural CD7 ligand SECTM-1 ( 71 ), and the dual targeting of CD38 and LMP1 ( 72 ). Shaw et al.…”

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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An “off-the-shelf” CD2 universal CAR-T therapy for T-cell malignancies

Cited by 14 publications

References 40 publications

“Next top” mouse models advancing CTCL research

“Next top” mouse models advancing CTCL research

CAR products from novel sources: a new avenue for the breakthrough in cancer immunotherapy

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

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