Biopolymer Immune Implants' Sequential Activation of Innate and Adaptive Immunity for Colorectal Cancer Postoperative Immunotherapy.

Abstract

Surgical resection is the first-line therapy for colorectal cancer (CRC). However, for advanced CRC, the curative effect of surgical resection is limited due to either local recurrence or distal metastasis. Postoperative in situ immunotherapy, presents a promising option for preventing tumor recurrence and metastasis, owing to the fact that surgeons have unique opportunities and direct access to the surgical site. Herein, a designed biopolymer immune implant for CRC post-surgical therapy, characterized with tissue adhesion, sustained drug release, and sequential elicitation of innate immunity, adaptive immunity, and immune memory effects, is reported. With gradual release of the loaded resiquimod (R848) and anti-OX40 antibody (aOX40), the immune implant can eradicate residual tumors post-surgery (with no tumor recurrence in 150 days), inhibit the growth of distal tumors and elicit immune memory effects to resist tumor re-challenge. Immunological analysis reveal that the biopolymer immune plant treatment leads to a two-stage action, with enhanced natural killer cells (NK cells) infiltration and activation of dendritic cells (DCs) in the first several days, then a greatly increased population of infiltrating T cells, and finally immune memory effects are established. The reported biopolymer immune implants provide a valuable and clinically-relevant option for post-surgical CRC management.