CAR+ T-cell therapy might serve as a new treatment option for Cisplatin resistant squamous cell carcinoma

Background Due to increasing prevalence of Cisplatin resistance in squamous cell carcinoma, new options for those treatment-refractory tumors are needed. Chimeric antigen receptor (CAR) T-cell therapy as an adoptive cellular immunotherapy may serve as a new therapeutic modality. In this study, we analyze whether Cisplatin resistance enhances CAR+ T-cell therapy in head and neck, urothelial and ovarian carcinoma.

Methods: In a first step, the antigen expression of the potential targets (EGFR, ErbB2, CD44v6) was detected by flow cytometry for Cisplatin sensitive and resistant matching sets of different squamous cell carcinoma cell lines (head and neck, urothelial, ovarian). Functional CAR constructs were lentivirally expressed in primary human T-cells. CAR+ T-cells were enriched and purified using the MACS ^® System and then co-cultured with the sets of tumor cell lines for 16h. Lysis of tumor cells was analyzed by MTT proliferation assay (n=4) to determine treatment efficacy. Results Flow-cytometry shows a heterogenic range of antigen-positive and negative tumor cell lines. After purification of T-cells, a 99 %  CAR+ T-cell fraction was used for the assay. The killing efficacy of the CAR+ T-cells correlates predominantly with the density of antigen expressed in the Cisplatin sensitive cell lines. In the resistant cell lines, the killing efficacy is either increased or stays at the same high level as in the sensitive cell lines.

Conclusion: The efficacy of CAR+ T-cell therapy is improved the in our Cisplatin resistant cell lines and therefore might be a beneficial alternative therapeutic option for treatment-refractory tumors.

Poster-PDF A-1198.pdf

Conflict of interest

Der Erstautor gibt keinen Interessenskonflikt an.

Publication History

Article published online:
13 May 2021