Tumors, like infectious agents, can change and evolve in an effort to escape immune detection. It has therefore been postulated that attempts to erradicate tumors could be greately improved by combining methods that focus on tumor ablation (chemotherapy, radiation therapy, surgery) with methods that enhance immune activity and boost tumor-specific immune responses. This project attempts to address this issue by determining the extent to which an orally administered polyphenylpropanoid polysaccharide complex (PPC) can function as a systemic immune adjuvant capable of boosting tumor-specific immune responses associated with chemotherapy-induced tumor antigen release. Based on observations that this complex induces the formation of human and mouse dendritic cells and functions as a potent adjuvant for DNA-, whole cell tumor-, and dendritic cell-vaccines, it is hypothesized that orally administered PPC will significantly enhance the in situ production of tumor-specific immune responses capable of suppressing, or even eradicating, residual tumor following chemotherapeutic-induced cell death. This hypothesis will be systematically addressed within the following specific aims.
Aim 1 : Using a non-immunosuppressive tumor debris-producing system (the Herpes simplex virus thymidine kinase/ganciclovir suicide/prodrug system) to model a traditional cancer treatment regime, we will determine the potential of orally administered PPC to boost the in situ production of anti-tumor immune response.
Aim 2 : A model of metastatic melanoma will be combined with the suicide gene/prodrug system to evaluate the ability of orally administered PPC to enhance the immune response against metastatic disease. And in Aim 3, the ability of PPC to enhance an in situ generated anti-tumor response in the presence of the potentially immunosuppressive chemotherapeutic agent, dacarbazine, will be evaluated. Ultimatety, the goal of this project is to learn how we can better create a state of immune activation and boost anti-tumor responses in patients with cancers.
| An, Wei-Wei; Kanazawa, Yasuko; Ozawa, Mutsumi et al. (2010) Dendritic cell differentiation and tumor cell apoptosis induced by components of a poly-phenylpropanoid polysaccharide complex. Anticancer Res 30:613-22 |
| Burrows, Mike; Assundani, Deepak; Celis, Esteban et al. (2009) Oral administration of PPC enhances antigen-specific CD8+ T cell responses while reducing IgE levels in sensitized mice. BMC Complement Altern Med 9:49 |
