Abstract 853: PDL1-PRAME dual antigen cancer vaccine inhibits melanoma growth in syngeneic mouse model and induces antigen-specific immune responses

Abstract Preferentially expressed antigen in melanoma (PRAME) is a cancer/testis antigen frequently expressed in various types of cancer, especially in melanoma, and its overexpression is associated with aggressive tumor progression. PRAME-specific T-cells found in cancer patients recognize and specifically lyse cancer cells, positioning PRAME as a promising target for cancer immunotherapy. PDL1 represents one of the most important immune checkpoint antigens frequently overexpressed on tumor cells to suppress T-cell mediated anti-cancer immunity. Several anti-PDL1 antibodies have been approved for clinical use through passive immunization. We had developed PDL1-PRAME dual antigen cancer vaccines and reported their promising tumor growth inhibition effects against syngeneic mouse hepatocellular carcinoma in 2023. In the present study, anti-cancer efficacy of the PDL1-PRAME dual antigen cancer vaccine was evaluated in an aggressive mouse melanoma model. Subcutaneous administration of the cancer vaccine formulated with alum-CpG oligodeoxynucleotides (ODNs) prior to tumor implantation significantly inhibited tumor growth by 91.5% (P<0.01) and prolonged the median survival time from 23.5 days to 40.5 days (P<0.01), compared to adjuvant treated control. To further optimize the vaccine formulation, another in vivo study was conducted with the PDL1-PRAME vaccine protein formulated with different adjuvants, including a novel synthetic saponin based adjuvant IAS-01, to evaluate the vaccine-induced antigen-specific immune responses in C57BL/6 mice. IAS-01, developed by ImmunAdd, is a liposome-based adjuvant incorporating two potent immunostimulants, a fully synthetic monophosphoryl Lipid A and a fully synthetic truncated QS-21 analogue, IA-05, devoid of hemolytic toxicity. Both alum-CpG ODN and IAS-01 obviously enhanced the vaccine-induced T-cell response against PRAME and elevated the anti-PDL1 antibody response. In particular, the highest anti-PDL1 antibody response was found with the IAS-01 adjuvant, compared to all the other adjuvants tested. Our study highlighted the prospect of developing the PDL1-PRAME dual antigen cancer vaccine for cancer immunotherapy. The vaccine efficacy is being further optimized in terms of its protein structure, adjuvant formulation, and administration route for potential clinical testing. Citation Format: Kin-Tak Chan, Hsin-Wei Chen, Pi-Hui Liang, You-Yu Lin, Tristan Zhang, Melvin Toh. PDL1-PRAME dual antigen cancer vaccine inhibits melanoma growth in syngeneic mouse model and induces antigen-specific immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 853.