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T-Cell Receptor–Based Immunotherapy for Hematologic Malignancies

Biernacki, Melinda A., MD*†; Brault, Michelle, PhD*; Bleakley, Marie, MD, PhD*‡

doi: 10.1097/PPO.0000000000000378
Review Articles
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Adoptive immunotherapy with engineered T cells is at the forefront of cancer treatment. T cells can be engineered to express T-cell receptors (TCRs) specific for tumor-associated antigens (TAAs) derived from intracellular or cell surface proteins. T cells engineered with TCRs (TCR-T) allow for targeting diverse types of TAAs, including proteins overexpressed in malignant cells, those with lineage-restricted expression, cancer-testis antigens, and neoantigens created from abnormal, malignancy-restricted proteins. Minor histocompatibility antigens can also serve as TAAs for TCR-T to treat relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. Moreover, TCR constructs can be modified to improve safety and enhance function and persistence of TCR-T. Transgenic T-cell receptor therapies targeting 3 different TAAs are in early-phase clinical trials for treatment of hematologic malignancies. Preclinical studies of TCR-T specific for many other TAAs are underway and offer great promise as safe and effective therapies for a wide range of cancers.

From the *Clinical Research Division, Fred Hutchinson Cancer Research Center; and

Departments of Medicine and

Pediatrics, University of Washington, Seattle, WA.

Conflicts of Interest and Source of Funding: M. Bleakley has received compensation from Miltenyi Biotec for presentations at conferences and corporate symposia pertaining to research unrelated to that presented in the current article. M. Bleakley and M.A.B. have filed a provisional patent application number 62/616,261 covering applications of T-cell immunotherapy for CBF AML. M. Bleakley has filed a provisional patent application number 62/399,291 covering applications of engineered T-cell receptor for targeting minor histocompatibility (H) antigen HA-1 and compositions for treating leukemia and PCT/US2017/053112 covering applications of T-cell receptors specific for minor histocompatibility (H) antigen HA-1 and uses thereof.

Reprints: Marie Bleakley, MD, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Mailstop D3-100, Seattle, WA 98109. E-mail: mbleakle@fredhutch.org.

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