Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine

Abstract

In clinical settings, cancer vaccines as monotherapies have displayed limited success compared to other cancer immunotherapeutic treatments. Nanoscale formulations have the ability to increase the efficacy of cancer vaccines by combatting the immunosuppressive nature of the tumor microenvironment. Here, we have synthesized a previously unexplored cationic polymeric nanoparticle formulation using polyamidoamine dendrimers and poly( d , l -lactic- co -glycolic acid) that demonstrate adjuvant properties in vivo. Tumor-challenged mice vaccinated with an adenovirus-based cancer vaccine [encoding tumor-associated antigen (TAA)] and subsequently treated with this nanoparticulate formulation showed significant increases in TAA-specific T cells in the peripheral blood, reduced tumor burden, protection against tumor rechallenge, and a significant increase in median survival. An investigation into cell-based pathways suggests that administration of the nanoformulation at the site of the developing tumor may have created an inflammatory environment that attracted activated TAA-specific CD8 + T cells to the vicinity of the tumor, thus enhancing the efficacy of the vaccine.

Advances and applications of nanoparticles in cancer therapy

“…130 Cationic polymeric NPs using PLGA-PAMAM structure exhibit robust adjuvant properties in cancer vaccines, suggesting the great potential of cationic nanomaterials in cancer treatment. 131…”

“…The dendritic cells (DCs) targeting ability of polymer NPs was effectively enhanced by glycosylation on PLGA, and the glycosylated PLGA group demonstrated 3.5‐fold higher DCs uptake efficiency in vitro compared to control 130 . Cationic polymeric NPs using PLGA‐PAMAM structure exhibit robust adjuvant properties in cancer vaccines, suggesting the great potential of cationic nanomaterials in cancer treatment 131 …”

Towards a simple in vitro surface chemistry pre-screening method for nanoparticles to be used for drug delivery to solid tumours

“…56 Different studies suggest that a modest negative surface charge appears to be favourable for circumvention of MPS clearance and improved blood compatibility, thereby extending blood circulation time and improving tumour delivery. 57,58 On the other hand, cationic nanocarriers were recently used for the improvement of tumour immunosurveillance 59 as well as, more specifically, the administration of cancer vaccines which preferentially target antigen presenting cells. 18 These findings were reflected by our in vitro system: whereas internalization of anionic MSN-COOH particles was still slightly higher in PC-3 vs. THP-1 cells, cationic MSN-NH 2 particles had a preference for THP-1 cells.…”

Engineered polymer‐based scaffold as an implantable therapeutic vaccine against melanoma

“…These include combinatorial therapy of vaccines with immune checkpoint inhibitors 10,11 and other chemo drugs, 12,13 neoantigen-based vaccine therapy, 14,15 and engineering novel adjuvants 16,17 or other delivery platforms for tumor antigens. [18][19][20] Recently there has been an interest in the delivery of antigens and other immunomodulatory molecules using engineered 3D scaffolds. [21][22][23] Biodegradable polymer scaffolds are a promising drug delivery platform for anticancer applications.…”

“…A number of strategies are being investigated to improve the T‐cell response to therapeutic cancer vaccines. These include combinatorial therapy of vaccines with immune checkpoint inhibitors 10,11 and other chemo drugs, 12,13 neoantigen‐based vaccine therapy, 14,15 and engineering novel adjuvants 16,17 or other delivery platforms for tumor antigens 18–20 . Recently there has been an interest in the delivery of antigens and other immunomodulatory molecules using engineered 3D scaffolds 21–23 .…”