Immunotherapy of Hematologic Malignancies
Helen Heslop
MDBaylor College of Medicine
Project Term: October 1, 2018 - September 30, 2023
The overall goal of this SCOR proposal is to develop and clinically validate T-cell immunotherapies designed to produce antitumor activity without the toxicities associated with intensive chemotherapy. The effectiveness of T-cell immunotherapy for leukemia and lymphoma has now been amply demonstrated. Studies conducted in our previous SCOR have already led to multicenter trials and orphan drug designation of EBV-specific T cells for the treatment of EBV-positive NHL and to commercial licensing of our genetically modified T cells and a genetic safety switch engineered into effector T cells.
Given our successful track record, we propose to develop approaches that will enable T-cell immunotherapies to overcome remaining obstacles to broader application. Our application comes from experienced investigators with strong records of interactive research, who have already designed “first-in-man” studies to address one or more of the pivotal questions central to the success of the program.
In this SCOR, Projects 1 and 2 continue their focus on EBV+ lymphoma and myeloma, respectively, but take the work in new directions, while Project 3 exploits recent technical advances to target a new malignancy, acute myeloid leukemia (AML).
In Project 1, Drs. Rooney, Heslop and Rouce will build on their success in the previous funding period where they developed a bank of “off-the-shelf” CAR-therapeutics targeting viral lymphomas.
In the last funding period of Project 2, Drs. Metelitsa, Leen and Lulla obtained clinical responses in myeloma patients using multispecific tumor-antigen specific T cells. They will be exploiting their novel oral vaccine to boost the activity of these T cells.
In Project 3, Drs. Brenner and Mamonkin will test a novel target for chimeric antigen receptor (CAR) T cells in AML patients: the C-Type lectin–like Molecule 1 (CLL-1) These 3 projects are all designed to test novel approaches to immunotherapy.
Every individual project while designed to broaden the applicability and efficacy of T-cell immunotherapy on its own merits will likely inform and modify the direction of other projects.