Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies in China. In particular, advanced/refractory ovarian cancer lacks effective targeted therapies due to the immunosuppressive and proangiogenic tumor microenvironment. Mesothelin (MSLN) has been found to be highly expressive in most EOC. Targeting MSLN by antibodies or chimeric antigen receptor-modified T (CAR-T) cells and immune checkpoint blockades as well as apatinib, an anti-angiogenic drug, have been used in patients with refractory ovarian cancer. Apatinib was reported to promote the infiltration of CD8(+) T cells in lung cancer. However, the combination therapy of CAR-T secreting anti-PD-1 antibody with apatinib in EOC has not been reported. Case presentation Here we report a case of refractory EOC in a patient who had relapsed after multiline chemotherapy. The patient received autologous T cells that contained sequences encoding single-chain variable fragments specific for MSLN and full-length antibody for PD-1 (alpha PD-1). The modified T cells were called alpha PD-1-mesoCAR-T cells. After infusion, the copy number and PD-1 antibody secretion of the CAR-T cells were increased in the blood. By application of multimodality tumor tracking, MRI of the liver showed shrinkage of metastatic nodules from average diameter of 71.3-39.1 mm at month 2. The patient achieved partial response and survived more than 17 months. IL-6 levels in the patient fluctuated from the baseline to 2-4-folds after treatment, but side effects were mild with only grade 1 hypertension and fatigue. Conclusion alpha PD-1-mesoCAR-T cell therapy combined with apatinib demonstrates a potential therapeutic effect on advanced refractory ovarian cancer.
基金:
Major National Science and Technology Projects from Ministry of Science and Technology of China [2018-ZX10302207-003, 2019YFC1316202]; Shanghai Cell Therapy Corporation [BZ1903]
第一作者机构:[1]Tongji Univ, Shanghai Peoples Hosp 10, Canc Ctr, Dept Med Oncol,Sch Med, Shanghai 200072, Peoples R China[2]Tongji Univ, Shanghai Dermatol Hosp, Dept Oncol, Shanghai 200072, Peoples R China
通讯作者:
通讯机构:[1]Tongji Univ, Shanghai Peoples Hosp 10, Canc Ctr, Dept Med Oncol,Sch Med, Shanghai 200072, Peoples R China[2]Tongji Univ, Shanghai Dermatol Hosp, Dept Oncol, Shanghai 200072, Peoples R China[3]Shanghai Cell Therapy Grp Corp, Cell Drug Business Unit, Shanghai 201805, Peoples R China[5]Shanghai Univ, Shanghai Mengchao Canc Hosp, Shanghai Cell Therapy Res Inst, Shanghai 201805, Peoples R China
推荐引用方式(GB/T 7714):
Fang Juemin,Ding Na,Guo Xinling,et al.αPD-1-mesoCAR-T cells partially inhibit the growth of advanced/refractory ovarian cancer in a patient along with daily apatinib[J].JOURNAL FOR IMMUNOTHERAPY OF CANCER.2021,9(2):doi:10.1136/jitc-2020-001162.
APA:
Fang, Juemin,Ding, Na,Guo, Xinling,Sun, Yan,Zhang, Zhiwei...&Xu, Qing.(2021).αPD-1-mesoCAR-T cells partially inhibit the growth of advanced/refractory ovarian cancer in a patient along with daily apatinib.JOURNAL FOR IMMUNOTHERAPY OF CANCER,9,(2)
MLA:
Fang, Juemin,et al."αPD-1-mesoCAR-T cells partially inhibit the growth of advanced/refractory ovarian cancer in a patient along with daily apatinib".JOURNAL FOR IMMUNOTHERAPY OF CANCER 9..2(2021)