some TCR results and difficulties building a TCR T cell30 Jan 2020 09:03
Based on a wide range of investigation of WT1-TCR-T cells, recently, the first clinical trial using WT1-TCR-modified T cells for leukemia therapy was reported. Tawara et al. [10] reported a study on HLA-A*24:02-TCR-T cells infused in eight patients with refractory AML and high-risk MDS to evaluate safety and elucidate the kinetics of the T cells. During the study period, the TCR-T cells could be detected in blood for approximately 2 months, and no adverse events involving normal tissue were observed. The persisting TCR-T cells maintained ex vivo peptide-specific immune reactivity. Four of five patients who had persistent T cells at the end of the study survived more than 12 months. These results were the first to demonstrate the potential application of WT1-specific TCR-T cells in the clinic. As known, unlike B cell leukemia, it is limited target therapies for AML, undoubtedly, WT1-TCR-T cells are promising to treat refractory and relapse AML patients, particularly for the older AML patients who are unable to receive HSCT.
Summary and future directions
The transfer of TCR genes into primary human T cells to endow their specificity toward leukemia cells is becoming an interesting tool for T cell immunotherapy for hematological malignancies. However, there is still much to be considered. Although the development of TCR-T cells began as early as the 90 s, their application falls behind that of CAR-T cells, which was thriving at the end of 20 century. The advantage of TCR-T cells may be the high level of avidity and efficacy of TCRs, which can be a valuable addition to current treatment options for patients suffering from insufficient extracellular low leukemia antigens [42]. The lower incidence of cytokine release syndrome may be another advantage of TCR-T cells as well. However, some challenges might include the following: (1) preventing mis-pairing between introduced and endogenous TCRs, causing off-target reactivity, (2) the choice of T cell subpopulations for gene transfer, (3) overcoming exhausted and senescent T cells in patients, enhancing transgenic T cells responding to antigens, and (4) the promotion of persisting gene-modified T cells in vivo [43,44,45]. After overcoming the limitation, TCR-T cells may have bright future for leukemia immunotherapy.
https://cancerci.biomedcentral.com/articles/10.1186/s12935-018-0720-y
Sign In
Follow the stocks
