Tumor surface antigens (TSAs) (TSA)

Tumor surface antigens (TSAs) recognized by instructive chimeric antigen receptors (iCARs) on engineered dendritic cells represent a novel class of therapeutic targets for cancer immunotherapy. Unlike traditional CAR-T cell therapies that directly kill tumor cells, iCAR-DCs are designed to utilize surface antigens—such as disialoganglioside GD2 or HER2—as bait to capture tumor-derived material and extracellular vesicles (Mohammadzadeh et al., Science Translational Medicine, 2025). Upon binding these antigens, the iCAR provides instructive signals (e.g., via CD40 or TLR domains) that trigger dendritic cell maturation and the subsequent priming of endogenous T cells against a broad spectrum of tumor antigens. This approach, often referred to as antigen-agnostic immunotherapy, aims to overcome the limitations of single-antigen targeting by promoting a polyvalent immune response. Preclinical studies have shown that iCAR-DCs can effectively delay tumor growth in immunotherapy-resistant models by enhancing antigen cross-presentation and cross-dressing (Ghasemi et al., Nature Communications, 2025).

Other names

Tumor-associated antigensTAAsTumor-specific antigensSurface-expressed tumor antigensBait antigens for iCAR-DCs

Instructive chimeric antigen receptors (iCARs) expressed on engineered dendritic cells (DCs) bind to tumor surface antigens, triggering DC maturation and the internalization of tumor-derived material (including extracellular vesicles). This process facilitates the cross-presentation and cross-dressing of tumor antigens to T cells, thereby initiating a robust and specific anti-tumor immune response.