Cancer immunotherapy is an emerging area, which takes advantage of patients’ own immune system to fight against cancer. Though a lot of promising results have been achieved, several challenges remain towards successful therapy. Cytotoxic T lymphocytes (CTLs) are crucial immune cells for infected/cancerous cell lysis and many cancer immunotherapy methods are aimed at inducing tumor specific CTL responses to fight against cancer. However, it is difficult to generate high affinity immune responses against endogenous tumor associated CTL epitopes due to the negative selection during CTL maturation. Besides, tumor cells may fail to express target antigens (known as antigen-loss variants, ALVs) on surface or reduce expression of major histocompatibility complex class I (MHC I), which make CTLs lose their targets causing therapy failure. To address these challenges, acetalated dextran polymer based pH responsive microparticles were used to encapsulate foreign high affinity CTL epitopes (CTLps) to tumor tissues. These microparticles can encapsulate and release CTLps in acidic tumor microenvironment to induce highly functional CTLs, which can destroy tumor cells as well as stromal cells presenting CTLps. Enhanced CTL activation was observed both<i> in vitro </i>and <i>in vivo</i>. Significant protection against tumor development in mice were observed on two solid tumor models. These acetalated dextran based microparticles for foreign CTLp delivery provide a promising new approach of cancer immunotherapy.

pH responsive polymer microparticles for cytotoxic T lymphocyte epitope delivery for cancer immunotherapy

256th National Meeting (2018)

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