Abstract 1763: Acute but not chronic LCMV infection generates immunity against abnormally expressed self-antigens on infected and tumor cells and protects against lung and lymphoid cancers in mice

Abstract

Therapeutic cancer vaccines have been tested for years but showed limited immunogenicity and clinical efficacy mainly because of the immunosuppressive environment generated by tumors. One approach for improving cancer vaccine efficacy would be to use them prior to cancer occurrence to strengthen immunosurveillance. This would ensure cancer elimination at the earliest stages of carcinogenesis and avoid cancer editing and escape. However, identifying antigens that can be incorporated into safe and effective prophylactic cancer vaccines remains a major challenge. Best candidates would be shared tumor-associated antigens (TAA) that are reproducibly and stably expressed on advanced tumors and premalignant lesions but not on normal tissues and that would induce antibodies and T cells causing tumor rejection without danger of autoimmunity. Antibodies and T cells specific for some well-known TAA have been found in individuals without cancer but with a history of acute infections and this pre-existing immunity has been associated with lowered lifetime risk for developing cancer while causing no obvious toxicity. We hypothesized that those immune responses were generated to self-antigens that are abnormally expressed on infected cells and again later on tumor cells, which we named disease-associated antigens (DAA)/tumor associated antigens (TAA), DAA/TAA. We tested this hypothesis here using two strains of lymphocytic choriomeningitis virus (LCMV): Armstrong (Arm) strain and CL-13 that cause acute and chronic infection in mice, respectively. Both strains elicited antibodies that recognized antigens on mouse lung (LLC) and lymphoid (EL4) tumors. Mice were later injected with tumor cells and Arm-infected mice controlled tumor challenge better than naïve controls, whereas the Cl-13 infection in mice had either no effect or promoted tumor growth. We characterized 5 DAA/TAA that were targets of this virus infection-elicited anti-tumor immunity using immunoprecipitation followed by 2D DIGE and mass spectrometry. Our results suggest that a vaccine based on DAA/TAA that are expressed on tumors and infected cells could confer protection against both cancer and a viral infection. Accordingly, we are currently immunizing mice with peptides derived from the 5 DAA/TAA. Mice responding to the vaccine will be given either tumors or LCMV and we will measure their response to both and the immune effector mechanisms mediating the response. Citation Format: Camille Jacqueline, Sarah Boothman, Jonathan S. Minden, Olivera J. Finn. Acute but not chronic LCMV infection generates immunity against abnormally expressed self-antigens on infected and tumor cells and protects against lung and lymphoid cancers in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1763.