2021
DOI: 10.1038/s41598-021-98716-z
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Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells

Abstract: Targeted pharmacologic activation of antigen-specific (AgS) T cells may bypass limitations inherent in current T cell-based cancer therapies. We describe two immunotherapeutics platforms for selective delivery of costimulatory ligands and peptide-HLA (pHLA) to AgS T cells. We engineered and deployed on these platforms an affinity-attenuated variant of interleukin-2, which selectively expands oligoclonal and polyfunctional AgS T cells in vitro and synergizes with CD80 signals for superior proliferation versus p… Show more

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Cited by 5 publications
(3 citation statements)
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“…Key binding residues mutation could lead to binding affinity change between HLA and peptides. Binding affinity change has been demonstrated as a biomarker of immunotherapy efficiency ( Kim et al, 2020 ; Seidel et al, 2021 ; Murata et al, 2022 ). For each patient, only SNP mutations are kept, if the SNP locates on the key binding site of HLA or peptide, then we separate them in one group, otherwise in the other group.…”
Section: Methodsmentioning
confidence: 99%
“…Key binding residues mutation could lead to binding affinity change between HLA and peptides. Binding affinity change has been demonstrated as a biomarker of immunotherapy efficiency ( Kim et al, 2020 ; Seidel et al, 2021 ; Murata et al, 2022 ). For each patient, only SNP mutations are kept, if the SNP locates on the key binding site of HLA or peptide, then we separate them in one group, otherwise in the other group.…”
Section: Methodsmentioning
confidence: 99%
“…CUE Biopharma developed Immuno-Selective Targeting and Alteration of T cells (Immuno-STATs), which were originally designed to prime and expand naïve and preexisting anti-cancer T cell repertoires by co-delivering an engineered IL-2 variant (IL-2v) [52]. Immuno-STATs consist of a bivalent peptide-HLA-I complex and multivalent co-stimulatory molecules (affinity-attenuated IL-2v) built on an Fc framework.…”
Section: Mous Et Al (2006) Redirected Anti-cmv Cd8 Pos T Cells To B-c...mentioning
confidence: 99%
“…Perhaps the most distinguishing feature of the developed aAPS is its ability to rescue the cognate cells from a state of comparative hyporesponsiveness. Most of the antigen-specific aAPCs or other similar pMHC-based immunotherapeutic reagents like the synTACs or ImmunoSTATs, while being able to activate and restimulate cognate T cells, have not been evaluated for their ability to reprogram these suboptimally responsive T cells [13,23]. The developed aAPS is characterized by repetitive incorporation of the signal 1 and signal 2 components on the dextran backbone, the ratio and spatial arrangement of which may be crucial in determining its similarity with the immunological synapse.…”
Section: Timulatory Ligands Was Able To Induce Rapid and Sustained St...mentioning
confidence: 99%