Regulatory path for the approval of cell products in Israel

Adoptive Cell Therapy (ACT) of Tumor Infiltration Lymphocytes (TIL) yields promising clinical results in metastatic melanoma patients, who failed standard treatments. Since Transitional Cell Carcinoma (TCC) has long been recognized as a malignancy responsive to immunotherapy, we explored the feasibility of TIL production for the treatment of TCC patients.

Multiple TIL cultures were isolated from tumor specimens of four TCC patients who underwent surgery. We were able to successfully establish TIL cultures from all patients.

Eight TIL cultures derived from four patients were further successfully expanded with a Rapid Expansion Procedure to treatment levels under current Good Manufacturing Practice (cGMP) conditions.

Phenotype analyses of TCC-derived TIL cultures showed similar functionality and distributions of CD4, CD8, CD28 and PD1 T cell sub-populations compared to TIL cultures derived from melanoma patients, previously treated at our center.

In addition approval of cell infusion products for clinical use requires intensive quality control and safety testing. We developed suitable assays to measure potency, purity, identity, stability and safety of the cells. All drug products passed the required tests.

Here we present the successful pre-clinical development of TIL for immunotherapy in the TCC cancer setting, as well as all necessary criteria required by ethics committees, to approve a cell product. Based on the results shown here, a requested for the approval of TIL ACT in TCC patients has been recently submitted to the Israeli Ministry of Health.