Curative by Design™
Each High Curative Potential™ (HCP) target has an associated toolbox of peptide antigens (T cell epitopes) for major HLA types allowing Verik to efficiently extend TCR-based HCP therapies to reach a diverse patient population.
T cell receptor
T cells are engineered to express T cell receptors (TCRs) for an HCP™ peptide antigen. The T cell finds and binds the antigen presented on the surface of the tumor cell, bound in the cleft of an HLA molecule. Recognition of the peptide antigen initiates T cell killing.
A type of protein expressed in the germline but not in normal tissue outside of the immune-protected testes. Not all germline antigens qualify as High Curative Potential™ target proteins. Qualification requires that the protein, when expressed, becomes essential to the perpetuation of cancer. One example is AKAP4, a scaffold protein that can take control of how a cancer cell uses energy. AKAP4 expression is reported in many epithelial cancers, at nearly all stages. The types of cancer include ovarian, breast, esophageal, colorectal, and prostate. Of note, it is one of the few cancer germline antigens that may also serve as a useful diagnostic for the presence and recurrence of lung cancer. As a T cell target, AKAP4 offers broad potential in the curative treatment of solid tumors.
A fusion is caused by chromosomal rearrangement. It creates a chimeric protein that then drives a pivotal cancer function. Our epitope candidates target neoantigens (novel amino acid sequence) as well as cancer germline antigens (CGA-specific amino acid sequence) within the fusion proteins. One such family of fusions involve the cancer germline protein NUT. First discovered to be part of a fusion protein that caused NUT midline carcinoma, a rare, lethal cancer, NUT fusions are being uncovered in other poorly differentiated, highly lethal tumors. If Verik's epitopes can be used to direct T cell killing to NUT fusion-positive tumors, we have the potential to save the lives of these patients.
An Auxiliary Protein target is one that targets a key enabler but not an essential protein. The expression is stringently specific, but their function will not in itself confer high curative potential. An example of this is LY6k, a CGA that enables the metastasis of breast cancer. Thus, it can serve as a useful companion target to AKAP4 or other breast cancer HCP targets.