In Situ Formed Fibrin Scaffold with Cyclophosphamide to Synergize with Immune Checkpoint Blockade for Inhibition of Cancer Recurrence after Surgery

Abstract

Unsatisfied cytoreductive surgery predicts worse clinical outcomes. Previous studies have found that cyclophosphamide (CTX) is a rhythmic immune modulator that can target suppressive regulatory immune cells and meanwhile enhance effector cells. Here, a therapeutic scaffold is engineered based on a fibrin hydrogel to codeliver CTX and anti‐PD‐L1 antibody (aPDL1) for the prevention of cancer recurrence postsurgery. It is demonstrated that the sequential release of CTX and aPDL1 from the fibrin hydrogel can lead to selective depletion of regulatory T cells (Treg) in the residual tumor, which would then synergize the immune checkpoint blockade therapy. The therapeutic benefit is demonstrated in an orthotopic breast tumor and an orthotopic ovarian tumor model after incomplete resection of primary tumors. In this work, the strategy provides a clinically valuable option for preventing cancer recurrence postsurgery.

In Situ-formed Fibrin Hydrogel Scaffold Loaded With Human Umbilical Cord Mesenchymal Stem Cells Promotes Skin Wound Healing

“…Our previous work demonstrated that the brin hydrogel scaffold possesses sustained drug release in vitro and in vivo [33]. This scaffold not only overcomes the limitations of traditional medical dressings but also provides a suitable microenvironment for hUC-MSC growth and transplantation for the treatment of skin wounds.…”

“…With its excellent biocompatibility and safety, the brin hydrogel is authorized by the Food and Drug Administration for use in the human body [31][32][33]. In this study, we engineered a brin hydrogel scaffold loaded with hUC-MSCs to be implanted into the wound area for the treatment of full-thickness skin defects in a mouse model, aiming to explore the wound healing effects of brin hydrogel scaffold loaded with hUC-MSCs.…”

Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

“…This hydrogel, as a successful cancer vaccine, generated a strong antigen-specific humoral response, and provided prophylactic efficacy against a murine B16/OVA melanoma [146]. In another study, Zhang et al fabricated fibrin hydrogel to delivery of CTX and anti-PDL1 for localized chemo-immunotherapy after the resection of primary tumors [147]. Maximized synergistic anticancer efficacy was obtained by different release kinetic of CTX and anti-PDL1 [147].…”

“…In another study, Zhang et al fabricated fibrin hydrogel to delivery of CTX and anti-PDL1 for localized chemo-immunotherapy after the resection of primary tumors [147]. Maximized synergistic anticancer efficacy was obtained by different release kinetic of CTX and anti-PDL1 [147].…”

Reducing PD-L1 expression with a self-assembled nanodrug: an alternative to PD-L1 antibody for enhanced chemo-immunotherapy

“…In recent decades, many old drugs with new uses have been reported for new drug discovery and development 17 - 19 . For example, several chemotherapeutic agents that have been in use for a long time, such as doxorubicin, cyclophosphamide, and mitoxantrone, can evoke immunogenic cells death 20 - 22 . Additionally, metformin (Met) is a prevalent drug for type 2 diabetes mellitus (T2DM) due to its effectiveness, safety, and cheap price 23 .…”