Co-localized delivery of nanomedicine and nanovaccine augments the postoperative cancer immunotherapy by amplifying T-cell responses

Abstract

Immunotherapy in solid tumors is limited by the poor immunogenicity of tumors and limited T-cell immune response, resulting in low patient response rate. To increase the efficiency of cancer immunotherapy, a unique synergistic combination cancer immunotherapy by co-localized delivery of cancer nanomedicine for enhancing the tumor immunogenicity and nanovaccine for augmenting the antitumor T-cell immunity was developed for post-surgical tumor treatment. The thermo-responsive, curcumin-loaded polymer nanoparticles (nanomedicine)-assembled hydrogel enabled the complete coverage of the surgical bed of primary tumor and the spatio-temporal delivery of cognate nanomedicines and encapsulated nanovaccines. Importantly, the nanomedicine efficiently induced the immunogenic cell death (ICD) of residual cancer cells, and consequently enhanced the tumor immunogenicity and sensitized the tumor to antitumor T-cell immunity. The cancer nanovaccine composed of antigenic peptide, CpG-ODN and cationic polymer nanoparticle significantly triggered the maturation of dendritic cells (DCs) and elicited potent vaccine-specific T-cell immune responses. Using highly malignant postoperative breast carcinoma 4T1 models, we found that the combination immunotherapy strategy strikingly amplified the level of systemic host T-cell immunity, promoted the infiltration of CD8⁺ T lymphocytes in tumor, and thus efficaciously attenuated the local tumor recurrence and pulmonary metastasis. Collectively, this work provided an advanced synergistic combination approach for post-surgical tumor immunotherapy. The self-assembled hydrogel should enable a broader combination of immunomodulating nanomedicines and vaccines for cancer immunotherapy.

Keywords: Cancer immunotherapy; Cancer vaccine; Drug delivery; Immunogenic cell death; Nanomedicine.