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…

CD155 blockade enhances allogeneic natural killer cell-mediated antitumor response against osteosarcoma

Background
Allogeneic bone marrow transplant (alloBMT) is curative for hematologic malignancies through the graft-versus-tumor (GVT) effect but has been ineffective for solid tumors like osteosarcoma (OS). OS expresses CD155 which interacts strongly w…

CD40L stimulates tumor-infiltrating B-cells and improves ex vivo TIL expansion

Background
Adoptive transfer of tumor-infiltrating lymphocytes (TIL) is now a Food and Drug Administration (FDA)-approved treatment for melanoma. While this is a major milestone, there is room for improvement to increase clinical response rates and to…

Potency-optimized CD28-activating bispecific antibody for the targeted treatment of Nectin-4 positive cancers

Background
T-cell costimulation is crucial for an effective and sustained antitumor immune response, and inadequate expression of costimulatory ligands within tumors can impair T-cell function. Bispecific antibodies (bsAbs) targeting a tumor-associate…

Flagellin engineering enhances CAR-T cell function by reshaping tumor microenvironment in solid tumors

Background
Adoptive cell therapy using genetically engineered chimeric antigen receptor (CAR)-T cells is a new type of immunotherapy that directs T cells to target cancer specifically. Although CAR-T therapy has achieved significant clinical efficacy …

IL-12-producing cytokine factories induce precursor exhausted T cells and elimination of primary and metastatic tumors

Background
Curative responses to immunotherapy require the generation of robust systemic immunity with limited toxicity. Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effe…

Long-term follow-up of BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma

Background
B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T-cell immunotherapy has shown promising results in the treatment of relapsed or refractory multiple myeloma (R/RMM). This study presents the updated long-term outco…

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