Abstract
Triple-negative breast cancer (TNBC) comprises lethal malignancies with limited treatment options. Chimeric antigen receptor T (CAR-T) cell therapy is an effective immunotherapeutic strategy that has demonstrated unprecedented efficacy in the treatment of hematological malignancies but has shown limited success in the management of some solid tumors. Many malignant tumors are related to increased expression of intercellular adhesion molecule-1 (ICAM1), providing a rationale for ICAM1-specific immunotherapies for the treatment of cancer. Here, we validated the expression of ICAM1 in TNBC tissues. Subsequently, we generated a phage-displayed single-chain variable fragment (scFv) library using splenocytes from ICAM1-immunized mice and selected a novel ICAM1-specific scFv, mG2-scFv. Using mG2-scFv as the extracellular antigen binding domain, we constructed ICAM1-specific CAR-T cells and demonstrated the robust and specific killing of TNBC cell lines in vitro. Most importantly, in the TNBC mouse model, ICAM1-specific CAR-T cells significantly reduced the growth of the TNBC tumor, resulting in long-term remission and improved survival. Together, these results indicated that ICAM1-specific CAR-T cells have high therapeutic potential against ICAM1-positive TNBC tumors.
Highlights
Triple-negative breast cancer (TNBC) is a type of breast cancer with high invasiveness and recurrence rate, accounting for 15–20% of all confirmed breast cancer cases [1]
Results showed that intercellular adhesion molecule-1 (ICAM1) staining in TNBC tissues was stronger and present in more cells compared with non-TNBC tissues (Figures 1A,B)
We found that ICAM1 mRNA expression was higher in TNBC compared with the adjacent normal breast tissue and other types of breast cancer
Summary
Triple-negative breast cancer (TNBC) is a type of breast cancer with high invasiveness and recurrence rate, accounting for 15–20% of all confirmed breast cancer cases [1]. The commonly used methods for treating TNBC are mainly surgery, chemotherapy, and radiotherapy [4]. These treatments usually lead to pancytopenia and other adverse events such as nausea and diarrhea [5]. CAR-T Therapy in TNBC between 5 and 23% [6]. Some targeted drugs have been put into preclinical and clinical trials for TNBC, but most of them have not achieved satisfactory therapeutic results [7, 8]. New and powerful therapies are urgently needed for TNBC patients
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call