T-celreceptor-gemodificeerde T-cellen: nieuwe cellulaire therapie voor hematologische maligniteiten?

Despite the undeniable successes of chimeric antigen receptor T cells in the treatment of numerous hematopoietic malignancies, instances in which this therapy shows limited effectiveness, such as in acute myeloid leukemia (AML), still exists. This situation has prompted a search for alternative cellular therapies for neoplastic diseases. T-cell receptor-engineered T cells (TCR-e T cells) represent another approach to cellular cancer therapy that relies on the genetic modifications of lymphocytes. They are designed to interact with endoplasmic tumor-associated antigens (TAAs) presented on the cell surface via the major histocompatibility complex. Hence, the therapeutic effect is restricted to individuals with a specific TAA overexpression in the context of particular human leukocyte antigen types. Although promising results and the first approvals of TCR-e T cells for the treatment of solid tumors have been reported, only a few phase I/II clinical trials have been registered in hematopoietic malignancies, and some were terminated before yielding conclusive results. The most investigated TAAs as targets for TCR-e T cells in hematopoietic malignancies include Wilms tumor 1 (WT1), preferentially expressed antigen in melanoma (PRAME), and minor histocompatibility antigen (MiHA) in patients with AML. Similarly, New York esophageal squamous carcinoma 1 (NY-ESO-1) and B-cell-specific coactivator OBF-1 (BOB1) markers have been targeted in patients with multiple myeloma. With promising preliminary results, TCR-e T cell therapies targeting WT1, PRAME, MiHA, NY-ESO-1, and BOB1 remain under development as therapeutic options for hematologic malignancies.