Effective CAR T-cell targeting of an MUC1 cleavage product

Background
We developed Chimeric antigen receptor (CAR) T cells targeting mucin 1 (MUC1)* (muk * (muk 1 star)), which is the tumor-associated growth factor receptor form of MUC1. Our antibody, MNC2, uniquely binds to MUC1* on cancer cells but does not…

B7-H3 and CSPG4 co-targeting as Pan-CAR-T cell treatment of triple-negative breast cancer

Purpose
Chimeric antigen receptor T (CAR-T) cell therapy is under clinical investigation in patients with metastatic triple-negative breast cancer (TNBC). However, the identification of targetable antigens remains a high priority to avoid toxicity and…

Adoptively transferred macrophages for cancer immunotherapy

Background
Macrophages have been classically associated with their innate immune functions of responding to acute injury or pathogenic insult, but they have been largely overlooked as primary initiators of adaptive immune responses. Here, we demonstra…

Onboard, tethered IL-12 boosts potency of the Tmod NOT gate and preserves selectivity

Background
To reach their full potential in cancer therapy, immune cells engineered with synthetic constructs must achieve the challenging dual objectives of potency and selectivity to overcome the key obstacle: non-specific cytotoxicity. These proble…

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…

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