Gao et al. performed a series of temporal in vivo and in vitro assays of antitumor memory T cells from immune oncotherapy-treated mice. Although mice effectively withstood rechallenge as early as 30 days after therapy, memory T cells did not maximally mature functional therapeutic efficacy or resistance to suppressor cells until 100 days after initial curative therapy. Both CD4+ and CD8+ cells were required. These results could guide vaccine strategies in which antitumor memory T cells are employed to prevent the emergence of dormant metastases.
BACKGROUND: Late metastases develop from cancer of the breast, prostate, lung, kidney and malignant melanomas. Memory T-cells have excellent potential to prevent this devastating development in the same way that they routinely prevent emergence of latent viruses. MATERIAL AND METHODS: A peritoneal tumor mouse model of viral oncotherapy was used to generate therapeutic antitumor memory T-cells. Functional in vivo and in vitro assays were used to study the temporal evolution of their anticancer effects. RESULTS: Highly therapeutic antitumor memory was generated by viral oncolytic immunotherapy 30 days after treatment and matured to maximal potency at 100 days. Maturation was not uniform across different measures. CONCLUSION: The results provide guidelines for developing a viral oncolytic vaccine strategy to generate antitumor memory T-cells that can eliminate small nests of metastatic cancer cells in sanctuary sites and prevent emergence of tumors from dormant cancer cell collections. The results are relevant to any immunization strategy designed to generate antitumor memory T-cells.
Author Info: (1) Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, U.S.A. (2) MMA-NMD Lab, Department of Pathology and La
Author Info: (1) Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, U.S.A. (2) MMA-NMD Lab, Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, American University Hospital, Beirut, Lebanon. (3) Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, U.S.A. ira.bergman@chp.edu. Department of Neurology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, U.S.A. Department of Immunology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, U.S.A.
