PDZ domains of PATJ facilitate immunological synapse formation to promote T cell activation

Background
The highly organized structures of the immunological synapse (IS) are crucial for T cell activation. PDZ domains might be involved in the formation of the IS by serving as docking sites for protein interactions. In this study, we investigat…

Precision enhancement of CAR-NK cells through non-viral engineering and highly multiplexed base editing

Background
Natural killer (NK) cells’ unique ability to kill transformed cells expressing stress ligands or lacking major histocompatibility complexes (MHC) has prompted their development for immunotherapy. However, NK cells have demonstrated on…

BCL-2 mutant B7H6-CAR-T cells synergized with venetoclax for treating small cell lung cancer

Background
Patients with small cell lung cancer (SCLC) generally have a poor prognosis, with an exceptionally high proliferative rate and a strong propensity for early metastasis, indicating the urgent need for novel therapies. The development of chim…

Development and optimization of Eva1 (MPZL2) targeting chimeric antigen receptor T cells

Background
Whereas chimeric antigen receptor gene modified T (CAR-T) cell therapy has been clinically applied to malignant lymphomas and multiple myeloma, CAR-T cell therapy for solid tumors has so far not reached clinical application. Epithelial V-li…

CD22 CAR-T cells secreting CD19 T-cell engagers for improved control of B-cell acute lymphoblastic leukemia progression

Background
CD19-directed cancer immunotherapies, based on engineered T cells bearing chimeric antigen receptors (CARs, CAR-T cells) or the systemic administration of bispecific T cell-engaging (TCE) antibodies, have shown impressive clinical responses…

Immunopeptidomics identified antigens for mRNA-lipid nanoparticle vaccines with alpha-galactosylceramide in multiple myeloma therapy

Background
Invariant natural killer T (iNKT) cells and CD8+ T cells are key in the immune response against multiple myeloma (MM), a largely incurable blood cancer. Immunization is a promising strategy to activate these T cell populations. To our knowl…

CLN-619, a MICA/B monoclonal antibody that promotes innate immune cell-mediated antitumor activity

Background
Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for the natural killer group 2 member D (NKG2D) receptor and are broadly expressed on tumor cells but minimally on normal tissues. When cytotoxic NKG2D-ex…

MARC, a novel modular chimeric antigen receptor, improves T cell-based cancer immunotherapies by preventing early T cell exhaustion and enhancing persistence

Background
Chimeric antigen receptor T cell (CAR-T)-based immunotherapies have reshaped the therapeutic landscape of cancer treatment, in particular for patients afflicted with leukemia. However, defects in CAR behaviors and clinical complications hav…

T-bet overexpression enhances CAR T cell effector functions and antigen sensitivity

Background
T cells modified to express a chimeric antigen receptor (CAR) are successful against B-lineage malignancies but fail to induce durable remissions in up to half of patients and have shown limited efficacy against other types of cancer. Strat…

Single-cell RNA sequencing of human double-negative T cells reveals a favorable cellular signature for cancer therapy

Background
Allogeneic double-negative T-cell (DNT) therapy has emerged as a novel, off-the-shelf cellular treatment with clinical feasibility, safety, and promising efficacy against leukemia. However, the biology of DNTs is less well characterized, an…

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