Gemcitabine Resistant Triple Negative Breast Tumor Derived Mesoporous Silicon Nanovaccine Overcame Drug Resistance

Abstract

Abstract Drug resistance presents a significant challenge in cancer treatment. By far, there is no effective method to solve this issue. Therapeutic cancer vaccine, which uses tumor antigens, e.g. neoantigens, to activate the hosts’ immune system to eliminate tumor cells, may be effective for overcoming tumor resistance. So, it is hypothesized that resistant tumors may have much more abundant tumor mutations in comparison to naive tumors, and the corresponding vaccine may overcome drug resistance. The proteomics data confirmes that cell lysates from resistant tumors to gemcitabine (GEM), a model drug, contain abundant tumor‐associated antigens, tumor‐specific antigens, damage‐associated molecular patterns, and neoantigens, which can activate immune responses. Herein, to enhance antigen presentation, a mesoporous silicon nanovaccine is developed, which is loaded with antigens from GEM treated GEM‐resistant triple‐negative breast cancer 4T1 cells. When mice bearing GEM‐resistant tumors are vaccinated, the nanovaccine displays efficacy against GEM‐resistant tumors. Moreover, when combined with immunotherapy, the efficacy of the developed nanovaccine on GEM‐resistant tumors are further improved by increasing intratumoral T‐cell infiltrations. The work presents a new strategy for overcoming drug resistance using cancer nanovaccine, which broadens clinical application prospects.