Combination of Immune Gene Therapy and Hematopoietic Stem Cell Transplantation Against Solid Cancer

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The central objective of cancer immunotherapy is to induce a tumor specific immune response, that is, an in vivo generation of a large number of highly reactive antitumor lymphocytes. However, solid cancers often show a weak immunogenicity and establish an immune-tolerant environment. Thus, the integration of two complementary immune therapies, immune gene therapy, which induces tumor-specific immunity, and hematopoietic stem cell transplantation (HSCT), which re-constructs a fresh immune system, may hold promise against solid cancers.

In autologous HSCT, lymphopenia-induced homeostatic proliferation (HP) of T cells is driven by the recognition of self antigens, and there is an opportunity to skew the T-cell repertoire during the T cell recovery by engaging tumor-associated antigens, leading to a break in tolerance against tumors. However, HP-driven antitumor responses decline rapidly in association with tumor growth. We hypothesize that a tumor-specific immune response induced by an immune gene therapy could enhance and sustain HP-induced antitumor immunity. When an allogeneic MHC plasmid was intratumorally injected at the early phase following syngeneic HSCT, the established tumors were markedly regressed and the survival of recipient mice was prolonged without significant toxicities. The results suggest the efficacy and safety of integrating immune gene therapy with an autologous HSCT for the treatment of solid cancers.