Multiple tumor-associated antigens on malignant T lymphocytes (Multi-TAA)

Multiple tumor-associated antigens on malignant T lymphocytes refers to a composite therapeutic target strategy used in the development of multi-specific immunotherapies for T-cell malignancies, such as T-cell lymphomas and leukemias. This approach targets a panel of antigens—most commonly PRAME, WT1, Survivin, NY-ESO-1, and MAGE-A4—that are overexpressed in malignant T cells relative to healthy tissues (ClinicalTrials.gov, NCT02201992; Marker Therapeutics, 2024). These antigens are typically intracellular proteins whose peptide fragments are presented on the cell surface via Major Histocompatibility Complex (MHC) molecules, allowing them to be recognized by the T-cell receptors (TCRs) of therapeutic T cells. By targeting multiple antigens simultaneously, this strategy aims to overcome the clonal heterogeneity of tumors and reduce the risk of antigen escape, a process where tumor cells evade the immune system by losing the expression of a single targeted protein (Lulla et al., 2016). This multi-antigen approach is primarily utilized in the production of non-genetically modified Multi-TAA T-cell therapies, which are designed to provide a broad, polyfunctional anti-tumor response. Clinical applications involve expanding a patient's or donor's own T cells ex vivo to recognize these specific peptide sequences before re-infusion. The strategy is intended to offer a more durable clinical response and a wider therapeutic window than therapies targeting a single lineage-specific marker. It also helps minimize the risk of widespread T-cell aplasia, which is a common side effect of pan-T-cell directed therapies like CD5 or CD7 CAR-T cells.

Other names

Multi-TAAMulti-antigen-specific T-cell targetsTumor-associated antigens in T-cell malignanciesPan-antigen T-cell targets

The mechanism involves the simultaneous targeting of a panel of tumor-associated antigens (TAAs) by ex vivo expanded T-lymphocytes. These therapeutic T cells utilize their native T-cell receptors (TCRs) to recognize peptide fragments of antigens such as PRAME, WT1, and Survivin presented by MHC molecules on the surface of malignant T lymphocytes. Upon recognition, the T cells exert direct cytotoxic effects, including the release of perforin and granzymes, leading to the apoptosis and lysis of the tumor cells (Lulla et al., 2016; Marker Therapeutics, 2024).