Cancer vaccines are an attractive option for improving disease-free survival following surgical resection of solid tumors. However, several clinical studies have shown that while cancer vaccines can routinely induce protection in a prophylactic model, the same vaccines often show only limited therapeutic efficacy. The tumor immunosuppressive network, formed by interactions between cancer cells and host immune cells, is a major obstacle to achieving complete tumor eradication. Myeloid-derived suppressor cells (MDSCs) can be considered critical players in tumor-induced immunosuppression in both animal models and cancer patients, which they have a remarkable ability to suppress the activation and proliferation of T cells. Therefore, the depletion of MDSCs would strengthen immunity of tumor-bearing mice.
Recently, Prof. Yong Taik LIM’s group of Sungkyunkwan University reported a novel implantable, engineered 3-dimensional porous scaffolds which were designed to generate synergistic action between MDSC-depleting agents and cancer vaccines consisting of whole tumor lysates and nanogel-based adjuvants. The local peritumoral implantation of the synthetic immune niche (termed immuneCare-DISC, iCD) as a post-surgical treatment in an advanced-stage primary 4T1 breast tumor model generated systemic anti-tumor immunity and prevented tumor recurrence at the surgical site as well as the migration of residual tumor cells into the lungs, resulting in 100% survival.
These therapeutic outcomes were achieved through the inhibition of immunosuppressive MDSCs in tumors and spleens by releasing gemcitabine and recruitment/activation of dendritic cells, enhanced population of CD4+ and CD8+ T cells, and increased IFN-γ production by cancer vaccines from the iCD. This combined spatiotemporal modulation of tumor-derived immunosuppression and vaccine-induced immune stimulation through the iCD is expected to provide an immune niche for preventing of postoperative tumor recurrence and metastasis.