treatment with targeted vesicular stomatitis virus generates therapeutic multifunctional antitumor memory cd4 t cells a generally applicable easytouse method of focusing a patients immune system to eradicate or prevent cancer has been elusive we are attempting to develop a targeted virus to accomplish these aims we previously created a recombinant replicating vesicular stomatitis virus vsv that preferentially infected her2neu expressing breast cancer cells and showed therapeutic efficacy in an implanted balbc mouse tumor model the current work shows that this therapy generated therapeutic antitumor cd4 t cells against multiple tumor antigens cd4 t cells transferred directly from cured donor mice could eradicate established tumors in host mice t cells were transferred directly from donor mice and were not stimulated ex vivo both tumors that expressed her2neu and those that did not were cured by transferred t cells analysis of cytokines secreted by antitumor memory cd4 t cells displayed a multifunctional pattern with high levels of interferon interleukin il4 and il17 antitumor memory cd4 t cells traveled to the mesenteric lymph nodes and were activated there treatment with targeted recombinant replicating vsv is a potent immune adjuvant that generates therapeutic multifunctional antitumor memory cd4 t cells that recognize multiple tumor antigens immunity elicited by viral therapy is independent of host major histocompatibility complex or knowledge of tumor antigens virusinduced tumor immunity could have great benefit in the prevention and treatment of tumor metastases