Targeting TACC3 Induces Immunogenic Cell Death and Enhances T-DM1 Response in HER2-Positive Breast Cancer.

Unlabelled: Trastuzumab emtansine (T-DM1) was the first and one of the most successful antibody-drug conjugates (ADC) approved for treating refractory HER2-positive breast cancer. Despite its initial clinical efficacy, resistance is unfortunately common, necessitating approaches to improve response. Here, we found that in sensitive cells, T-DM1 induced spindle assembly checkpoint (SAC)-dependent immunogenic cell death (ICD), an immune-priming form of cell death.

TCR-NK Cells: A Novel Source for Adoptive Immunotherapy of Cancer.

Antigen-specific retargeting of cytotoxic lymphocytes against tumor-associated antigens has thus far remained largely dependent on chimeric antigen receptors (CARs) that can be constructed by the fusion of an extracellular targeting domain (classically a single-chain variable fragment from an antibody) fused with intracellular signaling domains to trigger activation of T or natural killer (NK) cells. A major limitation of CAR-based therapies is that this technology only allows for the targeting of antigens that would be located on the surface of target cells while non-surface antigens, which affect approximately three-fourths of all human genes, remain out of reach. The targeting of non-surface antigens is only possible using inherent T cell receptor (TCR) mechanisms.

Targeting Adenosine with Adenosine Deaminase 2 to Inhibit Growth of Solid Tumors.

Extracellular adenosine in tumors can suppress immune responses and promote tumor growth. Adenosine deaminase 2 (ADA2) converts adenosine into inosine. The role of ADA2 in cancer and whether it can target adenosine for cancer therapy has not been investigated.

Engineering antigen-specific NK cell lines against the melanoma-associated antigen tyrosinase via TCR gene transfer.

Introduction of Chimeric Antigen Receptors to NK cells has so far been the main practical method for targeting NK cells to specific surface antigens. In contrast, T cell receptor (TCR) gene delivery can supply large populations of cytotoxic T-lymphocytes (CTL) targeted against intracellular antigens. However, a major barrier in the development of safe CTL-TCR therapies exists, wherein the mispairing of endogenous and genetically transferred TCR subunits leads to formation of TCRs with off-target specificity.