Cancer cells expressing mismatched Human Leukocyte Antigen (HLA) or tumor-associated antigens (TAA)

Cancer cells expressing mismatched Human Leukocyte Antigen (HLA) or tumor-associated antigens (TAA) refers to a cellular target population defined by the presence of specific surface markers or intracellular proteins presented via the Major Histocompatibility Complex (MHC). In the context of allogeneic hematopoietic stem cell transplantation, mismatched HLA molecules act as the primary targets for donor-derived T-cells, facilitating the "graft-versus-tumor" (GVT) effect which is crucial for eradicating residual malignancy (Appelbaum, 2001, Nature). Tumor-associated antigens (TAAs), such as MAGE-A4 or CD19, represent another class of targets that are either uniquely expressed or overexpressed by cancer cells compared to healthy tissues (Vigneron, 2015, BioMed Research International). These antigens are exploited by modern immunotherapies, including Chimeric Antigen Receptor (CAR) T-cells and T-cell receptor (TCR) engineered therapies, to direct cytotoxic immune responses specifically toward the tumor (June & Sadelain, 2018, N Engl J Med). While these strategies offer high specificity, they are associated with significant clinical challenges such as "on-target, off-tumor" toxicity and Cytokine Release Syndrome (CRS) (StatPearls, 2023). Furthermore, the loss of HLA expression or antigen shedding remains a primary mechanism of tumor escape and resistance to these therapies. Consequently, this target profile is central to the design of next-generation multispecific and allogeneic cellular products in oncology.

Other names

Allogeneic tumor cellsHLA-mismatched malignant cellsTAA-positive cancer cellsMHC-mismatched tumor cellsAntigen-expressing cancer cells

Recognition of mismatched HLA or tumor-associated antigens by engineered or donor-derived immune cells, leading to targeted lysis of the cancer cells through the release of perforins, granzymes, and pro-inflammatory cytokines.