Personalized neoantigen hydrogel vaccine combined with PD-1 and CTLA-4 double blockade elicits antitumor response in liver metastases by activating intratumoral CD8+CD69+ T cells.

Preclinical study using mouse models and human database analysis

“Then, the efficacy and corresponding antitumor molecular mechanisms of NPT-gels combined with programmed death receptor 1 and cytotoxic T-lymphocyte-associated protein 4 double blockade (PCDB) for the treatment of liver metastases were investigated using various preclinical liver metastasis models.”

Mice with liver metastasis models and human patients from the SEER database

“The effects of liver metastasis on survival and intratumor T-cell subpopulation infiltration in patients with advanced tumors were investigated using the Surveillance, Epidemiology, and End Results Program (SEER) database and immunofluorescence staining, respectively.”

33,933 human patients from SEER database and varying numbers of mice per experimental group

“data from SEER database on patients diagnosed with advanced breast (n=4531), lung (n=21 639), and colon (n=7763) cancers between 2015 and 2020 were analyzed.”

Up to 70 days for tumor burden monitoring in mice

“As shown in figure 4B–E, by monitoring tumor burden for up to 70 days, the combined therapy strategy showed significant tumor regression and better OS (both p<0.001) compared with E-NPT-gels/L-NPT-gels or PCDB treatment alone in both two liver metastases models.”

Liver metastases are associated with poorer 5-year survival and an immunosuppressive microenvironment characterized by low CD8+ T cells and high Tregs

“Liver metastases are associated with poorer 5-year overall survival, characterized by low infiltration of cytotoxic CD8+ T cells and high infiltration of regulatory T cells (Tregs).”

NPT-gels combined with PCDB enhanced antitumor efficacy and induced long-term immune memory in preclinical models

“Importantly, NPT-gels further combined with PCDB could enhance neoantigen-specific T-cell infiltration and effectively unlock the immunosuppressive microenvironment of liver metastases, showing superior antitumor efficacy and inducing long-term immune memory in various preclinical liver metastasis models without obvious toxicity.”

The combination therapy increased the infiltration of neoantigen-specific CD8+CD69+ T cells

“Mechanistically, the combined strategy can inhibit Tregs, induce the production and infiltration of neoantigen-specific CD8+CD69+ T cells to enhance the immune response, and potentially elicit antigen-presenting effects in Naïve B_Ighd+ cells and M1-type macrophages.”