Abstract
Vaccines to induce effective and sustained antitumor immunity have great potential for postoperative cancer therapy. However, a robust cancer vaccine simultaneously eliciting tumor-specific immunity and abolishing immune resistance continues to be a challenge. Here we present a personalized cancer vaccine (PVAX) for postsurgical immunotherapy. PVAX is developed by encapsulating JQ1 (a BRD4 inhibitor) and indocyanine green (ICG) co-loaded tumor cells with a hydrogel matrix. Activation of PVAX by 808 nm NIR laser irradiation significantly inhibits the tumor relapse by promoting the maturation of dendritic cells and eliciting tumor infiltration of cytotoxic T lymphocytes. A mechanical study reveals that NIR light-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to the satisfied therapeutic effect. Furthermore, PVAX prepared from the autologous tumor cells induces patient-specific memory immune response to prevent tumor recurrence and metastasis. The PVAX model might provide novel insights for postoperative immunotherapy.
Highlights
Vaccines to induce effective and sustained antitumor immunity have great potential for postoperative cancer therapy
We demonstrate that administration of the PVAX through local injection followed by NIR laser-triggered activation efficiently prevent postoperative tumor recurrence and metastasis by simultaneously boosting patientspecific immune responses and blocking programmed death ligand 1 (PD-L1)-dependent immune evasion
The results showed that treatment by FK@IQ-4T1+L at the distant site moderately inhibited the recurrence of 4T1 primary tumor (Supplementary Fig. 17a–c), suggesting tumor-specific delivery of JQ-1 is critical for tumor recurrence prevention by suppressing PD-L1-mediated immune evasion
Summary
Vaccines to induce effective and sustained antitumor immunity have great potential for postoperative cancer therapy. PVAX prepared from the autologous tumor cells induces patient-specific memory immune response to prevent tumor recurrence and metastasis. Immunotherapy using peptide-based vaccines or checkpoint inhibitors has induced durable clinical response in several types of tumors including melanoma, lung and bladder cancers[11, 12]. The autologous tumor cell source obtained from patients can release patient-specific antigens to trigger antitumor immunity and achieve personalized immunotherapy[22, 23]. We demonstrate that administration of the PVAX through local injection followed by NIR laser-triggered activation efficiently prevent postoperative tumor recurrence and metastasis by simultaneously boosting patientspecific immune responses and blocking PD-L1-dependent immune evasion. The simple PVAX fabrication procedure combined with its ability to simultaneously induce a patient-specific immune response, and combat immunological resistance, supports its potential as a robust cancer vaccine for post-surgical immunotherapy
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