2. Academic Validation
  3. Celecoxib Augments Paclitaxel-Induced Immunogenic Cell Death in Triple-Negative Breast Cancer

Celecoxib Augments Paclitaxel-Induced Immunogenic Cell Death in Triple-Negative Breast Cancer

  • ACS Nano. 2024 Jun 18;18(24):15864-15877. doi: 10.1021/acsnano.4c02947.
Xiaohui Qian 1 2 3 4 5 6,  Huang Yang 7,  Ziqiang Ye 7,  Bingqiang Gao 1 2 3 4 5 6,  Zhefeng Qian 1 2 3 4 5 6,  Yuan Ding 1 2 3 4 5 6,  Zhengwei Mao 1 2 7,  Yang Du 1 2 3 4 5 6,  Weilin Wang 1 2 3 4 5 6
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.
  • 2 Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, Zhejiang, China.
  • 3 Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, Zhejiang, China.
  • 4 National Innovation Center for Fundamental Research on Cancer Medicine, Hangzhou 310009, Zhejiang, China.
  • 5 Cancer Center, Zhejiang University, Hangzhou 310058, Zhejiang, China.
  • 6 ZJU-Pujian Research & Development Center of Medical Artificial Intelligence for Hepatobiliary and Pancreatic Disease, Hangzhou 310058, Zhejiang, China.
  • 7 MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, Zhejiang, China.
PMID: 38829727 DOI: 10.1021/acsnano.4c02947
Abstract

Triple-negative breast Cancer (TNBC) is a highly aggressive malignancy that lacks effective targeted therapies. Inducing immunogenic cell death (ICD) in tumor cells represents a promising strategy to enhance therapeutic efficacy by promoting antitumor immunity. Paclitaxel (PTX), a commonly used chemotherapy drug for TNBC, can induce ICD; however, the resulting immunogenicity is limited. Thus, there is an urgent need to explore strategies that improve the effectiveness of ICD in TNBC by incorporating immunoregulatory agents. This study investigated the potential of celecoxib (CXB) to enhance PTX-induced ICD by blocking the biosynthesis of PGE2 in the tumor cells. We observed that the combination of CXB and PTX promoted the maturation of dendritic cells and primed a T cell-dependent immune response, leading to enhanced tumor rejection in a vaccination assay. To further optimize drug delivery in vivo, we developed cRGD-modified liposomes for the targeted codelivery of CXB and PTX. This delivery system significantly improved drug accumulation and triggered robust antitumor immunity in an orthotopic mouse model of TNBC. Moreover, it served as an in situ vaccine to inhibit tumor recurrence and lung metastasis. Overall, our findings provide in-depth insights into the therapeutic mechanism underlying the combination of CXB and PTX, highlighting their potential as effective immune-based therapies for TNBC.

Keywords

celecoxib; drug combination; immunogenic cell death; nanomedicine; triple-negative breast cancer.

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