An off-the-shelf, T-cell receptor (TCR)-less CD19 CAR T-cell product showed positive results in preclinical specificity, functionality, and efficacy studies, according to data presented at the AACR Annual Meeting 2018 (April 14-18, 2018; Chicago, IL).
FT819 could potentially be made more accessible to cancer patients than conventional CAR T-cell therapies, explained Bob Valamehr, PhD, vice president of Cancer Immunotherapy, Fate Therapeutics Inc Donor.
FT819 cells started with cells from a healthy donor rather than the patient. This created a master cell line, which was used to produce large quantities of CAR19 T-cells (FT819) that are not patient-restricted. The master cell line used to manufacture FT819 is an induced pluripotent stem cell (iPSC) line that provides distinct advantages over autologous and allogenic approaches.
Conventional CAR T-cell therapies use autologous T-cells and new approaches under investigation are using donor T-cells, Valamehr explained. T-cells can attack the patient’s tissues and organs, resulting in a potentially severe and fatal immune system reaction known as graft-vs-host disease (GvHD). The removal of the TCR from these donor T-cells is crucial in order to avoid GvHD.
In addition to CAR-targeting CD19-positive tumor cells, FT819 also has a second targeting receptor designed to broaden the therapy’s efficacy. The CD16 Fc receptor can bind to tumor cells coated with antibodies. This enables FT829 to be administered in combination with other proven cancer treatments, such as monoclonal antibodies targeting CD20-positive tumor cells, to potentially overcome antigen escape.
FT819 displayed an efficient cytotoxic T-cell response when challenged with CD19-positive tumor cells by producing cytokines and mediators of cell death, in studies in vitro. FT819 was also found to be target-specific by attacking only CD19-positive tumor cells and sparing CD19-negative tumor cells. Through the expression of CD16 Fc receptor, FT819 was shown to elicit antibody-dependent cell-mediated cytotoxicity when combined with a therapeutic antibody targeting CD20.
“Through the development of FT819, we believe there is significant opportunity to lower the cost of CAR T-cell manufacture; enhance the quality of the product; and create a readily available supply of a more efficacious product to reach more patients in need,” said Valamehr.
“FT819 cells were developed using human cells, but the studies used model systems that are not predictive of clinical safety and efficacy,” Valamehr concluded. “We will be required to conduct human clinical trials to fully assess the safety and efficacy of our off-the-shelf iPSC-derived CAR T-cell products.”.—Janelle Bradley
Click the link for more AACR 2018 coverage: AACR Annual Meeting 2018