Synergizing CXCL9 with BRD4‐PROTAC Using Nanochaperone Boosts Robust T Cell‐Dependent Antitumor Immune Responses for Cancer Immunotherapy
Source abstract
Abstract
Abstract The efficacy of cancer immunotherapy is greatly restricted by insufficient infiltration of cytotoxic T lymphocytes and immunosuppressive microenvironment in tumor tissue. Here a potent strategy to address the limitations by combination therapy of chemokine (CXCL9) with BRD4‐PROTAC (dBET6) using the unique mixed‐shell polymeric micelle (MSPM)‐based nanochaperone (nChap) delivery platform is reported. CXCL9 significantly enhances the intratumoral infiltration of CD8+ T cells while dBET6 induces tumor cell immunogenic cell death (ICD) and downregulates the interferon‐γ (IFNγ)‐triggered programmed death ligand 1 (PD‐L1) expression, synergizing to boost robust T cell‐dependent antitumor immunity responses to enhance cancer immunotherapy is demonstrated. Moreover, this nano‐CXCL9/dBET6 exhibits reduced systemic toxicity, prolonged half‐life, and enhanced tumor accumulation in comparison to free drugs. This study provides a promising strategy for efficient cancer immunotherapy.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: CAR-T cell therapy research · Cancer Immunotherapy and Biomarkers · Immunotherapy and Immune Responses
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Key Laboratory of Functional Polymer Materials of Ministry of Education Institute of Polymer Chemistry Tianjin Key Laboratory of Functional Polymer Materials State Key Laboratory of Medicinal Chemical Biology Frontiers Science Center for New Organic Matter College of Chemistry Nankai University Tianjin 300071 P. R. China
Haihe Laboratory of Sustainable Chemical Transformations Tianjin 300192 P. R. China
Funding
National Key Research and Development Program of China · National Natural Science Foundation of China
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