Injectable cryogel-based whole-cell cancer vaccines

Abstract

A biomaterial-based vaccination system that uses minimal extracorporeal manipulation could provide in situ enhancement of dendritic cell (DC) numbers, a physical space where DCs interface with transplanted tumor cells, and an immunogenic context. Here we encapsulate GM-CSF, serving as a DC enhancement factor, and CpG ODN, serving as a DC activating factor, into sponge-like macroporous cryogels. These cryogels are injected subcutaneously into mice to localize transplanted tumor cells and deliver immunomodulatory factors in a controlled spatio-temporal manner. These vaccines elicit local infiltrates composed of conventional and plasmacytoid DCs, with the subsequent induction of potent, durable, and specific anti-tumor T cell responses in a melanoma model. These cryogels can be delivered in a minimally invasive manner, bypass the need for genetic modification of transplanted cancer cells, and provide sustained release of immunomodulators. Altogether, these findings indicate the potential for cryogels to serve as a platform for cancer cell vaccinations.

Designing hydrogels for controlled drug delivery

“…The macropores can allow cell infiltration and incorporation of payloads after gelation. The potential for this approach has been demonstrated with alginate and gelatin cryogels that were injected subcutaneously into mice to deliver immunomodulatory factors in a controlled manner 64 , which led to regression of established tumors. Despite having many advantages, interconnected pores may significantly reduce the diffusion length for drug release and the volume fraction of polymer, potentially leading to release that is too rapid and limited drug loading capacity.…”

The role of myeloid cells in cancer therapies

“…53) or the β-catenin pathway 54 . Implanting physical scaffolds that incorporate a combination of immunoregulatory components into tumour-bearing subjects could be useful to optimize tumour-infiltrating DC activation in situ [210][211][212] .…”

Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors

“…We found that serum lipase activity was also lower in the mice that were treated with cdGMP/CAR T cell scaffolds compared with untreated tumor-bearing mice (82 U/l ± 4.5 versus 128 U/l ± 10.85; P = 0.003). While a reference range for comparison of serum lipase activity in mice is not available, the reduced enzyme activity might indicate an exocrine pancreatic insufficiency due to the destruction or loss of acinar cells; however, a histological correlate for this was not found ( Figure 8F, left panel), and 3 weeks vaccines, clinicians have developed biomaterial-based platforms that can carry patient-specific tumor cells or tumor lysates along with immune-stimulating biomolecules (38,39). Following s.c. implantation, these biomaterials attract circulating APCs, which take up the tumor antigens incorporated in the matrix, and then mature and emigrate into regional lymph nodes where they can prime T cells that are specific for the cancer.…”