T-Cell Receptor-Engineered Cells for the Treatment of Hematologic Malignancies.
Recent attention in adoptive immunotherapy for hematologic malignancies has focused on lymphocytes expressing chimeric antigen receptors. An alternative technique to redirect the immune system toward cancer cells involves the use of T-cells carrying an engineered tumor-recognizing T-cell receptor (TCR). This approach allows targeting of surface or intracellular/nuclear proteins as long as they are processed and presented on the cell surface by human leukocyte antigen molecules. Several trials in advanced solid tumors, particularly melanoma and synovial sarcoma, support the validity of this strategy, although tumor responses have often been short-lived. Emerging data from patients with multiple myeloma and myeloid neoplasms suggest that the benefit of TCR-modified cells may extend to blood cancers. Methodological refinements may be necessary to increase the in vivo persistence and functionality of these cells. Particularly with affinity-enhanced TCRs, however, more effective therapies may increase the potential for serious toxicity due to the unexpected on- or off-target reactivity.
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Nasheed M
NM
Hossain
Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D2-190, Seattle, WA, 98109-1024, USA.|Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA.
Aude G
AG
Chapuis
Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D2-190, Seattle, WA, 98109-1024, USA. rwalter@fredhutch.org.|Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA. rwalter@fredhutch.org.|Department of Epidemiology, University of Washington, Seattle, WA, USA. rwalter@fredhutch.org.
Roland B
RB
Walter
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D060846:Cell Engineering; D064987:Cell- and Tissue-Based Therapy; D015789:HLA-A2 Antigen / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D015789:HLA-A2 Antigen; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell
Adoptive immunotherapy; Cell engineering; Hematologic malignancy; Immunotherapy; T-cell receptor