Abstract 3685: Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

Abstract

Abstract Introduction Cancer immunotherapy, the utilization of patients’ own immune system to treat cancer, has emerged as a powerful new strategy in cancer treatment. The main limitation of this strategy is the low long-term durable response rate. Therefore, there has been high interest in developing strategies to further improve cancer immunotherapy. We hypothesized that antigen-capturing nanoparticles (AC-NPs) could improve immune responses to checkpoint inhibitor. The NPs can induce the abscopal effect by capturing tumor antigens released during radiotherapy and improve the presentation of antigens to professional antigen presenting cells (APCs). Methods We developed several types of antigen-capturing NPs (AC-NPs) using poly (lactic-co-glycolic acid) (PLGA), a biocompatible and biodegradable polymer. The surfaces of nanoparticles were modified to enable capturing tumor antigens released after radiotherapy. Unmodified PLGA NPs absorb antigens via hydrophobic-hydrophobic interactions. AC-NPs with positive charged bind antigens through ionic interactions. AC-NPs having maleimide group on the surface (Mal AC-NP) bind to antigens by reaction to thiol groups of antigens. The B16-F10 tumor, a syngeneic mouse melanoma model on C57BL/6 mice was employed to evaluate the efficacy of AC-NPs to improve immune responses of checkpoint inhibitor combining radiotherapy. Results The in vivo efficacy study showed that AC-NPs can significantly improve the efficacy of αPD-1 treatment in the B10F10 melanoma model, which generates up to 20% cure rate as compared to 0% without AC-NP. Mechanistic studies demonstrated that the AC-NPs can drain to lymph node and be took up by APCs, which indicate that they are able to deliver captured antigens during radiotherapy to APCs. In the meantime, it was found that there are significant increases in CD4+ and CD8+ T cell to Treg ratios, which indicate an expansion of the T-helper cells and cytotoxic T cells. We also found that AC-NPs can induce increased level of antitumor cytokine interferon-γ (IFN-γ) following stimulation ex vivo, which implied that AC-NPs were able to elicit systemic T cell activation. Therefore, a novel strategy for improving cancer immunotherapy with nanotechnology was presented by our work. Acknowledgements The authors would also like to thank our funding sources. A.Z.W., J.E.T., S.T., and J.M.D are supported by funding from the National Institutes of Health/National Cancer Institute (U54CA198999, Carolina Center of Cancer Nanotechnology Excellence (CCNE)-Nano Approaches to Modulate Host Cell Response for Cancer Therapy). B.V. is supported by funding from UNC University Cancer Research Fund, Paul Calabresi Oncology K12 Award and UNC CCNE Pilot Grant. A.Z.W. is also supported by funding from the NIH/NCI (U54 CA151652 and R01 CA178748) for this work. A.Z.W. was also supported by funding from the NIH/NCI (R21 CA182322). Citation Format: Yuanzeng Min. Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3685. doi:10.1158/1538-7445.AM2017-3685