Song, Phuengkham, and Kim et al. developed a shear-sensitive, self-assembling, injectable gel (iGel) composed of multi-nanodomain vesicles efficiently loaded with controlled releasable hydrophilic and hydrophobic drugs and cationic nanoliposomes. Delivery of iGel containing gemcitabine, imiquimod, and clodronate to the post-surgical tumor bed in 4T1 and TC-1 mouse models increased T cell infiltration and activation, reduced suppressive immune cell types, and inhibited primary tumor regrowth and lung metastases. iGel generated immunological memory and systemic immunity against distant tumors, and synergized with checkpoint blockade.
Contributed by Alex Najibi
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.