Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma

Abstract

Vaccination with a virus-expressed cDNA library derived from normal prostate cells can cure established prostate cancer in mouse models. Pulido et al. extend this approach and identify specific tumor-associated antigens from tumor-derived virus-expressed cDNA libraries that can be used in combination to cure established melanoma in mice. Multiple intravenous injections of a cDNA library, derived from human melanoma cell lines and expressed using the highly immunogenic vector vesicular stomatitis virus (VSV), cured mice with established melanoma tumors. Successful tumor eradication was associated with the ability of mouse lymphoid cells to mount a tumor-specific CD4+ interleukin (IL)-17 recall response in vitro. We used this characteristic IL-17 response to screen the VSV-cDNA library and identified three different VSV-cDNA virus clones that, when used in combination but not alone, achieved the same efficacy against tumors as the complete parental virus library. VSV-expressed cDNA libraries can therefore be used to identify tumor rejection antigens that can cooperate to induce anti-tumor responses. This technology should be applicable to antigen discovery for other cancers, as well as for other diseases in which immune reactivity against more than one target antigen contributes to disease pathology.