Syringeable immunotherapeutic nanogel reshapes tumor microenvironment and prevents tumor metastasis and recurrence

Abstract

The low response rate of current cancer immunotherapy suggests the presence of few antigen-specific T cells and a high number of immunosuppressive factors in tumor microenvironment (TME). Here, we develop a syringeable immunomodulatory multidomain nanogel (iGel) that overcomes the limitation by reprogramming of the pro-tumoral TME to antitumoral immune niches. Local and extended release of immunomodulatory drugs from iGel deplete immunosuppressive cells, while inducing immunogenic cell death and increased immunogenicity. When iGel is applied as a local postsurgical treatment, both systemic antitumor immunity and a memory T cell response are generated, and the recurrence and metastasis of tumors to lungs and other organs are significantly inhibited. Reshaping of the TME using iGel also reverts non-responding groups to checkpoint blockade therapies into responding groups. The iGel is expected as an immunotherapeutic platform that can reshape immunosuppressive TMEs and synergize cancer immunotherapy with checkpoint therapies, with minimized systemic toxicity.

Viral nanoparticles for drug delivery, imaging, immunotherapy, and theranostic applications

“…The anti-CD47 and CPMV acted synergistically to combat tumor growth. And just recently, we demonstrated the synergistic effects of combining CPMV with checkpoint inhibitors, such as anti-programmed cell death-1 [120].…”

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

“…By provoking a CD8+ T cell response through medullary macrophages, the CHP-based vaccine was proved the promising immunotherapeutic effect in animal models [136]. Unlike the directed induction of apoptosis or autophagy by the cytotoxic drugs, vaccine adjuvants or immunomodulators typically trigger antitumor immunity by regulating the tumor microenvironment [137][138][139]. However, the limitations of tumor immunotherapy include the high cost of therapy, the difficulty of sustained systematic immunity, and low patient response.…”

Infiltrating Immune Cells in Gastric Cancer: A Novel Predicting Model for Prognosis

“…International Publisher revealed that many solid tumors are associated with immune cell infiltration in the tumor immune microenvironment (TIME) which affects therapy efficacy and overall survival to no small extent [7][8][9]. A study revealed that high T-cell subsets density in gastric cancer was associated with prolonged survival [10].…”