CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infltrating lymphocytes in ovarian cancer
Thanks to the initiative and financial support of Ovacure, complemented with the scientific input of the Anticancer Fund, the team of Prof. Inge-Marie Svane from the Center for Cancer Immune Therapy, Herlev Hospital at the University of Copenhagen in Denmark started developing an innovative treatment for women with recurrent ovarian cancer.
The treatment consists of collecting immune cells (T-cells) from the patient own's tumour, multiplying (expanding) them and reinjecting them in the same patient. This is known as adoptive T-cell transfer.
In a pilot study, the researchers showed that adoptive T-cell transfer was feasible and well-tolerated in patients with ovarian cancer. However, the immune effect of the T-cells was not as potent as initially expected.
To address this problem, the Danish team worked on further improving the manufacturing of the T-cells. In the microenvironment of ovarian cancer, some immune checkpoint molecules (such as CTLA-4) can lead to the inactivation of the T-cells. By inhibiting CTLA-4 during the preparation and production of the T-cells to be re-administered to the patient, the T-cells become more potent.
These results are reported in the publication CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infltrating lymphocytes in ovarian cancer. This led these researchers to initiate a new clinical trial combining this adoptive T-cell transfer with an immunotherapy drug (https://clinicaltrials.gov/ct2/show/NCT03287674).