In situ chemoimmunotherapy hydrogel elicits immunogenic cell death and evokes efficient antitumor immune response

• Published in: Journal of translational medicine 2024-04, Vol.22 (1), p.341-341, Article 341
• Main Authors: Liu, Qin, Xu, Rui, Shen, Jingwen, Tao, Yaping, Shao, Jingyi, Ke, Yaohua, Liu, Baorui
• Format: Article
• Language: English
• Subjects: Albumin; Alginic acid; Analysis; Animals; Antigens; Antitumor activity; Biochemistry; Breast cancer; Breast carcinoma; Cancer; Cancer therapies; Carcinoma, Hepatocellular; Cell death; Cell Line, Tumor; Chemoimmunotherapy; Chemotherapy; Controlled release; Effector cells; Gels (Pharmacy); Health aspects; Hepatocellular carcinoma; Hydrogel; Hydrogels; Hydrogels - pharmacology; Hydrogels - therapeutic use; Imiquimod - pharmacology; Imiquimod - therapeutic use; Immune response; Immunity; Immunogenic Cell Death; Immunogenicity; Immunological memory; Immunotherapy; Immunotherapy - methods; In situ vaccine; Laboratory animals; Liver cancer; Liver Neoplasms - drug therapy; Lymphatic system; Lymphocytes; Lymphocytes T; Memory cells; Metastases; Mice; Monoclonal antibodies; Nab-PTX; Nanoparticles; Paclitaxel; Patient outcomes; Penicillin; Pharmaceuticals; Sodium; Sodium alginate; T cells; TLR7 agonist; Toxicity; Tumor cells; Tumor Microenvironment; Tumors; Vaccines
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-024-05102-0

Chemoimmunotherapy has shown promising advantages of eliciting immunogenic cell death and activating anti-tumor immune responses. However, the systemic toxicity of chemotherapy and tumor immunosuppressive microenvironment limit the clinical application. Here, an injectable sodium alginate hydrogel (ALG) loaded with nanoparticle albumin-bound-paclitaxel (Nab-PTX) and an immunostimulating agent R837 was developed for local administration. Two murine hepatocellular carcinoma and breast cancer models were established. The tumor-bearing mice received the peritumoral injection of R837/Nab-PTX/ALG once a week for two weeks. The antitumor efficacy, the immune response, and the tumor microenvironment were investigated. This chemoimmunotherapy hydrogel with sustained-release character was proven to have significant effects on killing tumor cells and inhibiting tumor growth. Peritumoral injection of our hydrogel caused little harm to normal organs and triggered a potent antitumor immune response against both hepatocellular carcinoma and breast cancer. In the tumor microenvironment, enhanced immunogenic cell death induced by the combination of Nab-PTX and R837 resulted in 3.30-fold infiltration of effector memory T cells and upregulation of 20 biological processes related to immune responses. Our strategy provides a novel insight into the combination of chemotherapy and immunotherapy and has the potential for clinical translation.