A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors

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.

Materials for Immunotherapy

“…In the same year, Figdor and co‐workers made a polyisocyanopeptide hydrogel, which displayed reversible and thermally induced gelation, for improved T cell expansion and delivery . Li and co‐workers developed a postoperative vaccine using a peptide‐based hydrogel loaded with whole tumor cells collected from tumor resections . By locally injecting the gel into the tumor bed after resection and stimulating with NIR light, tumor‐specific antigens were released along with anti‐PD‐1.…”

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

“…Wang et al developed a personalized cancer vaccine (PVAX) by encapsulating the bromodomain and extraterminal protein BRD4 inhibitor (JQ1) to mediate PD-L1 checkpoint blockade and ICG co-coated tumor cells into a hydrogel matrix (Figure 10a,b). [293] ICG was applied to qualify PVAX with NIR light-triggered release profile (Figure 10c), as well as NIR light-promoted intratumoral penetration ability. PVAX demonstrated to induce the immune memory effect to prevent metastasis after vaccination (Figure 10d-f).…”

Laser adjuvant for vaccination

“…Wang et al recently showed that a personalized cancer vaccine encapsulating JQ1, a bromodomain‐containing protein 4 (BRD4) inhibitor, and ICG along with tumor cells in a hydrogel matrix inhibited the tumor relapse by promoting the maturation of dendritic cells and eliciting tumor infiltration of cytotoxic T lymphocyte (CTL) upon 808 nm laser treatment (Changchun New Industries Optoelectronics Tech. Co., Ltd, Changchun, China) for 2 minutes at an irradiance of 2.0 W/cm 2 . In this system, temperature increase in the treated area with 808 nm near‐infrared (NIR) laser triggered on‐demand release of tumor‐specific antigens and cytokine expression, subsequently facilitating the activation of dendritic cells.…”

“…Co., Ltd, Changchun, China) for 2 minutes at an irradiance of 2.0 W/cm 2 . 39 In this system, temperature increase in the treated area with 808 nm near-infrared (NIR) laser triggered on-demand release of tumor-specific antigens and cytokine expression, subsequently facilitating the activation of dendritic cells. Interestingly, since the group did not observe the comparable DC maturation with heat generation only, the immune response seems to have been caused by increased release of tumor antigens, not photothermal effect.…”