Tumor-associated antigen-specific cytotoxic T cells (TAA-Ts)

Tumor-associated antigen-specific cytotoxic T cells (TAA-Ts) are a form of cellular immunotherapy where T cells are selected or engineered to recognize specific antigens that are preferentially expressed on cancer cells. Unlike tumor-specific antigens (TSAs) which are found exclusively on cancer cells, tumor-associated antigens (TAAs) may also be expressed at lower levels on some normal cells. TAA-Ts can be generated from a patient's own peripheral blood and expanded ex vivo before being reinfused. These cells can target various antigens such as Wilms tumor gene 1 (WT1), preferentially expressed antigen of melanoma (PRAME), and survivin. Clinical trials have shown that TAA-Ts can induce responses in some patients with relapsed or refractory solid tumors with minimal toxicity. The effectiveness of TAA-Ts depends on several factors, including the level of antigen expression on tumor cells, the ability of the T cells to infiltrate the tumor, and the tumor microenvironment. Research continues to focus on enhancing the potency and persistence of these cells, as well as identifying optimal antigen targets for different cancer types.

Other names

Tumor-reactive T cellsTumor-infiltrating lymphocytes (TIL) with TAA specificityTAA-specific T cellsAntigen-specific T-cell immunotherapy

TAA-Ts recognize tumor-associated antigens presented on MHC class I molecules on the surface of cancer cells. Upon recognition, these T cells bind to the peptide-MHC complex via their T cell receptor, become activated and release cytotoxic molecules (perforins, granzymes), induce apoptosis in the target cancer cells, release cytokines that enhance the broader immune response, and may lead to epitope spreading, where immune responses develop against additional tumor antigens.