A carboxymethyl dextran-based polymeric conjugate as the antigen carrier for cancer immunotherapy

BACKGROUND: Antigen-specific cytotoxic T lymphocytes (CTLs), which eliminate target cells bearing antigenic peptides presented by surface major histocompatibility complex (MHC) class I molecules, play a key role in cancer immunotherapy. However, the majority of tumors are not immunologically rejected since they express self-antigens which are not recognized by CTLs as foreign. To foreignize these tumors for CTL-mediated immunological rejection, it is essential to develop carriers that can effectively deliver foreign antigens to cancer cells. METHODS: A polymeric conjugate, composed of a carboxymethyl dextran (CMD) as the backbone and ovalbumin (OVA) as a model foreign antigen, was prepared to investigate its potential as the antigen carrier for cancer immunotherapy. RESULTS: An in vitro cellular uptake study showed that the conjugate was successfully taken up by TC-1 cervical cancer cells. When CMD-OVA was systemically administered to tumor-bearing mice, the strong fluorescence signal was observed at the tumor site over the whole period of time period, suggesting high tumor targetability of the conjugate. Compared to free OVA, CMD-OVA induced significantly higher antigen presentation at the tumor site. CONCLUSIONS: The CMD-OVA conjugate can effectively deliver the antigen to the tumor site, implying its high potential as the antigen carrier for cancer immunotherapy.