In situ vaccination: Harvesting low hanging fruit on the cancer immunotherapy tree

Abstract

After 100 years of debate, it is clear that cancer is recognized by the immune system and this has generated immense interest in cancer immunotherapy. The systemic nature of the immune system gives immunotherapy the ability to treat metastatic disease, which currently requires chemotherapy that frequently fails. Like chemotherapy, most immunotherapy is systemically applied in an effort to generate systemic antitumor immune response. However, local administration of immunostimulatory reagents into a recognized tumor by in situ vaccination (ISV) can also generate systemic antitumor immunity to fight metastatic disease. Conventional vaccines contain antigens and immune adjuvants. With ISV, the tumor itself supplies the antigen and the treatment only applies immune adjuvant directly to the tumor. While current immunotherapy often fails to eliminate cancer because of local immunosuppression mediated by tumors, effective ISV changes the tumor microenvironment from immunosuppressive to immunostimulatory, stimulates presentation of tumor antigens by antigen-presenting cells to T cells, and generates systemic antitumor immunity that promotes antigen-specific effector T-cell attack of both treated and importantly, untreated metastatic tumors. The advantages of ISV are: simple and cost-effective; minimal systemic side effects; feasible and flexible adjuvant delivery; exploiting all tumor antigens in the tumor avoids the need to identify antigens; utilizing all antigens in the tumor minimizes immune escape; and potential synergy when combined with other therapies. This review puts ISV into the broader context of cancer immunotherapy, including the use of nanoparticles, and outlines research needed in order to manifest the potential of ISV for clinical use. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Keywords: adjuvant; antigen; antigen-presenting cell; antitumor immunity; cancer immunotherapy; chemotherapy; effector T cells; immune escape; immunogenic tumor cell death; immunostimulatory; immunosuppression; in situ vaccination; metastatic; nanoparticles; presentation; tumor antigen; tumor microenvironment.