Anti-mesothelin CAR-T Immunotherapy Could be Effective in Ovarian Cancer

Findings from a recent study revealed the efficacy of the antimesothelin (MSLN CAR-T) treatment strategy in ovarian cancer and provided preliminary data for the expansion of additional clinical trials (Cancer Immunology, Immunotherapy. 2022. doi:10.1007/s00262-022-03238-w).

Jiannan Chen, MD Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China and colleagues wrote, “Numerous challenges remain for the effective use of CAR-T to treat solid tumors, including ovarian cancer, which is an aggressive and metastatic cancer with a poor therapeutic response.”

During the study, researchers tested for an effective anti-MSLN single-chain Fv antibody with comparable binding activity and non-off-target properties utilizing human phage display library. They also designed and created a second-generation of anti-MSLN CAR.

The researchers indicated that they demonstrated the efficacy of their anti-MSLN CAR-T for ovarian cancer treatment in an in vitro experiment to kill ovarian tumor cell lines. The anti-MSLN CAR-T obstructed MSLN-positive tumor growth concomitant with a substantial increase in cytokine levels compared with the control.

The researchers also noted that the efficacy of anti-MSLN CAR-T in an in vivo experiment against ovarian cancer cell-derived xenografts was demonstrated. Additionally, three cases of ovarian cancer were treated with autologous anti-MSLN CAR-T and assessed the safety and effectiveness of adoptive cell therapy.

The researchers revealed that in this investigator-initiated clinical trial, no patients experienced cytokine release syndrome or neurological symptoms over 2 grads and disease stabilized in two patients, with progression-free survival times of 5.8 and 4.6 months. After infusion, each time transient CAR expression was discovered in patient blood. The tumor partially subsided, and the patient’s condition was eased.

“This work proves the efficacy of the anti-MSLN CAR-T treatment strategy in ovarian cancer and provides preliminary data for the development of further clinical trials”, concluded the authors.