Terry J. Fry , M.D., Nirali N. Shah , M.D., Rimas J. Orentas , Ph.D., Maryalice Stetler-Stevenson , M.D., Ph.D., Constance M. Yuan , M.D., Ph.D., Sneha Ramakrishna , M.D., Pamela Wolters , Ph.D., Staci Martin , Ph.D., Cindy Delbrook , R.N., Bonnie Yates , P.N.P., Haneen Shalabi , D.O., Thomas J. Fountaine , M.D., Jack F. Shern , M.D., Robbie G. Majzner , M.D., David F. Stroncek , M.D., Marianna Sabatino , M.D., Yang Feng , Ph.D., Dimiter S. Dimitrov , Ph.D., Ling Zhang , Ph.D., Sang Nguyen , Haiying Qin , M.S., Boro Dropulic , Ph.D., Daniel W. Lee , M.D., Crystal L. Mackall , M.D.
20 November 2017
Chimeric antigen receptor (CAR) T-cells targeting CD19 mediate potent effects in relapsed/refractory pre-B cell acute lymphoblastic leukemia (B-ALL) but antigen loss is a frequent cause of resistance to CD19-targeted immunotherapy. CD22 is also expressed on most B-ALL and usually retained following CD19 loss. We report results from a phase I trial testing a novel CD22-CAR in twenty-one children and adults, including 17 previously treated with CD19-directed immunotherapy. Dose dependent anti-leukemic activity was observed with complete remission in 73% (11/15) of patients receiving ≥ 1 × 10 6 CD22-CART cells/kg, including 5/5 patients with CD19dim/neg B-ALL. Median remission duration was 6 months. Relapses were associated with diminished CD22 site density that likely permitted escape from killing by CD22-CART cells. These results are the first to eastablish the clinical activity of a CD22-CAR in pre-B cell ALL, including in leukemia resistant to anti-CD19 immunotherapy, demonstrating comparable potency to CD19-CART at biologically active doses in B-ALL. They also highlight the critical role played by antigen density in regulating CAR function. (Funded by NCI Intramural Research Program)