Harnessing T-cell activity against prostate cancer: A therapeutic microparticulate oral cancer vaccine

Abstract

Prostate Cancer specific immunotherapy in combination with immune stimulating adjuvants may serve as a viable strategy for facilitating tumor regression and preventing recurrence. In this study, an oral microparticulate vaccine encapsulating tumor associated antigens (TAA) extracted from a murine prostate cancer cell line, TRAMP-C2, was formulated with the help of a spray dryer. Microparticles were characterized in vitro to determine their physicochemical properties and antigenicity. Formulated microparticles had an average size of 4.92 ± 0.5 μm with a zeta potential of 7.92 ± 1.2 mV. In order to test our formulation for its ability to demonstrate adequate antigen presentation and co-stimulation, microparticles were tested in vitro on murine dendritic cells. In vitro biological characterization demonstrated the activation of specific immune system markers such as CD80/86, CD40, MHC-I and MHC-II. Following in vitro characterization, in vivo anti-tumor efficacy of the oral microparticulate vaccine was evaluated in C57BL/6 male mice. Combination therapy of vaccine microparticles with cyclophosphamide and granulocyte macrophage-colony stimulating factor (GM-CSF) demonstrated a five-fold reduction in tumor volume as compared to non-vaccinated mice. At the cellular level, cyclophosphamide and GM-CSF augmented the vaccine response as indicated by the reduced tumor volume and significant elevation of cytotoxic T-cell (CTL) CD8+ and (T-helper) CD4+ T-cells compared to mice receiving vaccine microparticles alone. Furthermore, our studies indicate a significant reduction in T-regulatory cells (T-regs) in mice receiving vaccine along with GM-CSF and cyclophosphamide, one of the immune escape mechanisms linked to tumor growth and progression. Thus, oral microparticulate vaccines have the potential to trigger a robust anti-tumor cellular response, and in combination with clinically relevant agents, significantly resist tumor growth and progression.