Cancer Vaccines Targeting WT1 for CCA

Cancer immunotherapy has emerged as a powerful tool in the treatment armamentarium of many cancer types. T cells are critical mediators of the antitumor immune response that specifically recognizes essential tumor-expressing proteins or antigens through their T-cell receptors to destroy tumor cells. Given that cholangiocarcinoma (CCA) is an immunogenic tumor, immunotherapy is a rational and promising treatment option.¹

At the Cholangiocarcinoma Foundation 2024 Annual Conference, Benjamin L. Green, MD, discussed the potential role of tumor vaccination strategies, particularly Wilms’ tumor 1 (WT1) peptide vaccines, for treating CCA.

Dr Green noted that antibody-based molecular immunotherapy may have a limited role in CCA due to lower T-cell numbers, which diminish T-cell–based immune responses to the tumor. On the other hand, he stated that peptide vaccines targeting specific tumor peptides may train the body’s immune system to recognize and destroy the peptide-bearing tumor naturally.

In mouse models of hepatocellular carcinoma, Dr Green’s research focused on developing an AFP499 peptide vaccine that significantly induced T-cell activation and ultimately reduced tumor burden in mice exposed to the vaccine. Encouraged by these results, it was hypothesized that a peptide vaccine targeting a rational CCA-specific protein would be a viable immunotherapy strategy for CCA.

The WT1 protein was selected as the most viable target for peptide vaccine therapy because it is expressed in many tumor types, including CCA. WT1 was overexpressed in approximately 20% of patient samples in intrahepatic CCA, thereby representing a potential target in these patients.

Dr Green’s group has identified a WT1-expressing CCA cell line that they propose implanting in mice to grow CCA and developing a WT1 peptide vaccine to treat the mouse CCA model.

He concluded that peptide vaccines can help boost the anti-cancer immune system in gastrointestinal cancers and that ongoing efforts are focused on further optimizing the WT1 peptide vaccine to define its role in CCA.²

References

1. Manthopoulou E, Ramai D, Dhar J, et al. Cholangiocarcinoma in the era of immunotherapy. Vaccines (Basel). 2023;11(6):1062.
2. Green BL. A peptide vaccine targeting WT1 for cholangiocarcinoma. Cholangiocarcinoma Foundation 2024 Annual Conference. Presented April 17-19, 2024. Accessed June 6, 2024.