Biomineralized hydrogel DC vaccine for cancer immunotherapy: A boosting strategy via improving immunogenicity and reversing immune-inhibitory microenvironment

Abstract

The postoperative recurrence and metastasis of triple negative breast cancer (TNBC) remain one fatal reason for the failure of clinical treatments. Although the rise of immunotherapy has brought hopes for reducing postoperative recurrence and potential metastasis, the low immune response and immunosuppression of tumor microenvironment (TME) still restrain its extensive application. Herein, we reported a boosting strategy by improving immunogenicity and reversing suppressive TME to realize efficient immunotherapy of TNBC. In this work, a CaCO3 biomineralized hydrogel DC vaccine was synthesized by fixing the membrane proteins of 4T1 cells-DCs fusion cells (FP) into biomineralized silk fibroin hydrogel. On one side, the FP-containing biomineralized hydrogel vaccine (SH@FP@CaCO3) has increased immunogenicity by providing a wide variety of tumor-associated antigens (TAAs) and realizing long-term protein release for DCs maturation and T cell activation. On the other side, the introduction of CaCO3 would increase the pH of TME and promote the polarization of M2-type macrophages to M1-type macrophages, thus reversing the immune-inhibitory microenvironment and relieving the immunosuppressive effect on T cells. The results indicate that the biomineralized hydrogel vaccine shows excellent immune activation effects by simultaneously enhancing the immunogenicity and reversing the immunosuppression TME, which provides a promising strategy for cancer immunotherapy.