Author(s): Patel RB, Ye M, Carlson PM, Jaquish A, Zangl L, Ma B, Wang Y, Arthur I, Xie R, Brown RJ, Wang X, Sriramaneni R, Kim K, Gong S, Morris ZS. Development of an in situ cancer vaccine via combinational radiation and bacterial-membrane-coated nanoparticles. Adv Mater. 2019 Oct;31(43):e1902626. doi: 10.1002/adma.201902626. Epub 2019 Sep 16. PMID 31523868
Journal: Advanced Materials (Deerfield Beach, Fla.), Volume 31, Issue 43, Oct 2019
Neoantigens induced by random mutations and specific to an individual’s cancer are the most important tumor antigens recognized by T cells. Among immunologically “cold” tumors, limited recognition of tumor neoantigens results in the absence of a de novo antitumor immune response. These “cold” tumors present a clinical challenge as they are poorly responsive to most immunotherapies, including immune checkpoint inhibitors (ICIs). Radiation therapy (RT) can enhance immune recognition of “cold” tumors, resulting in a more diversified antitumor T-cell response, yet RT alone rarely results in a systemic antitumor immune response. Therefore, a multifunctional bacterial membrane-coated nanoparticle (BNP) composed of an immune activating PC7A/CpG polyplex core coated with bacterial membrane and imide groups to enhance antigen retrieval is developed. This BNP can capture cancer neoantigens following RT, enhance their uptake in dendritic cells (DCs), and facilitate their cross presentation to stimulate an antitumor T-cell response. In mice bearing syngeneic melanoma or neuroblastoma, treatment with BNP+RT results in activation of DCs and effector T cells, marked tumor regression, and tumor-specific antitumor immune memory. This BNP facilitates in situ immune recognition of a radiated tumor, enabling a novel personalized approach to cancer immunotherapy using off-the-shelf therapeutics.