Abstract A030: Development of acid responsive microparticles for cytotoxic T-lymphocyte based antitumor immunotherapy

Cytotoxic T lymphocytes (CTL) can have remarkable abilities to kill tumor cells. However, the establishment of successful CTL based anticancer therapy has met many challenges, which include 1) difficulties in generating highly functional CTLs targeting endogenous tumor associated CTL epitopes; 2) the existence of antigen-loss variant subpopulation within cancer cells, which fail to express the targeted antigen and can escape the immune pressure bestowed by the specific CTLs; and 3) the reduced expression of major histocompatibility complex class I (MHC-I) molecules on tumor cells due to immune editing. To address these difficulties, a new approach is developed to deliver foreign high affinity CTL epitopes to tumor tissues utilizing pH responsive “smart” microparticles (MPs). These MPs could encapsulate CTL peptide, release the peptide under acidic condition encountered in tumor tissues, and enhance CTL activation. Mice bearing existing solid tumor were administered intratumorally with MPs containing the CTL peptide, which showed 100% survival following the treatment. In contrast, all control mice died from tumor. Significant protection from tumor induced death was also observed with systemic administration of CTL peptide-MPs. The therapeutic efficacy can be attributed to enhanced delivery of the epitope to tumor tissues, presentation of the epitope by tumor cells as well as tumor stromal cells and/or generation of epitope specific CTLs by the peptide containing MPs. These findings offer a promising new direction for treating established solid tumor using CTL therapy. Citation Format: Xuefei Huang, Herbert Kavunja, Shuyao Lang, Suttipun Sungsuwan, Zhaojun Yin. Development of acid responsive microparticles for cytotoxic T-lymphocyte based antitumor immunotherapy [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A030.