0000000000372891
AUTHOR
Matthias Wolfl
Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain
Adoptive transfer of T lymphocytes transduced with a T cell receptor (TCR) to impart tumor reactivity has been reported as a potential strategy to redirect immune responses to target cancer cells (Schumacher, T.N. 2002. Nat. Rev. Immunol. 2:512-519). However, the affinity of most TCRs specific for shared tumor antigens that can be isolated is usually low. Thus, strategies to increase the affinity of TCRs or the functional avidity of TCR-transduced T cells might be therapeutically beneficial. Because glycosylation affects the flexibility, movement, and interactions of surface molecules, we tested if selectively removing conserved N-glycoslyation sites in the constant regions of TCR alpha or …
Increasing Functional Avidity of T Cell Receptor (TCR)-Redirected T Cells by Removing Defined N-Glycoslyation Sites in the Constant Domain of Introduced TCR Chains.
Abstract Adoptive transfer of T lymphocytes transduced with a TCR to impart tumor reactivity has been reported as potential strategy to redirect immune responses to target cancer cells. However, the affinities of most TCRs specific for shared tumor antigens that can be isolated are usually low, in part reflecting the nature of the targeted tumor antigens which are self-proteins. Thus strategies that can increase the affinity or functional avidity of TCRs to be used in therapy to transduce T cells might be therapeutically beneficial. However, current strategies for increasing TCR affinity require extensive and usually random mutagenesis followed by screening the many derived mutations, and m…
Facilitating matched pairing and expression of TCR chains introduced into human T cells.
AbstractAdoptive transfer of T lymphocytes is a promising treatment for a variety of malignancies but often not feasible due to difficulties generating T cells that are reactive with the targeted antigen from patients. To facilitate rapid generation of cells for therapy, T cells can be programmed with genes encoding the α and β chains of an antigen-specific T-cell receptor (TCR). However, such exogenous α and β chains can potentially assemble as pairs not only with each other but also with endogenous TCR α and β chains, thereby generating αβTCR pairs of unknown specificity as well as reducing the number of exogenous matched αβTCR pairs at the cell surface. We demonstrate that introducing cy…