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Posted On: 06/02/2024 12:03:18 PM
Post# of 36519
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There's a brief mention of AE37 in this paper. The paper covers many different therapies for TNBC.
AE37 Synthetic Peptide Vaccine
The heart of the AE37 vaccine is a peptide hybrid of a HER2-derived peptide, AE36 (aa776-790), and a portion of the MHC Class II invariant chain (Ii), the LRMK Ii-Key core segment. This hybrid peptide is given with granulocyte–macrophage colony-stimulating factor (GM-CSF). Previous in vitro or preclinical studies identified an intracellular domain of HER2 (777–789) able of provoking a robust CD8 + cytotoxic T cell response [54, 55]. The immunogenicity of this peptide was attributed to its capacity to induce both HLA class I restricted responses and HLA class II restricted T cell help [56, 57].
The other portion of the AE37 hybrid peptide originates from the MHC Class II invariant chain (Ii), a protein that binds to newly minted MHC Class II molecules in the ER to prevent the binding of peptides destined for presentation by MHC Class I molecules. Only a small portion of Ii (aa 77–80 (LRMK) is needed to regulate the opening of MHC class II peptide binding groove. When the immunogenic HER peptide (AE36) is fused to the Ii (LRMK) peptide, the AE37 vaccine peptide is obtained [33].
For clinical use in the experimental treatment of TNBC patients (e.g. NCT04024800), AE37 will be administered intradermally as a bare peptide in three 21-day cycles for 5 cycles. Pembrolizumab will be given concomitantly with bare peptide, but then extended for an additional 30 cycles.
https://link.springer.com/article/10.1007/s12609-024-00552-3
AE37 Synthetic Peptide Vaccine
The heart of the AE37 vaccine is a peptide hybrid of a HER2-derived peptide, AE36 (aa776-790), and a portion of the MHC Class II invariant chain (Ii), the LRMK Ii-Key core segment. This hybrid peptide is given with granulocyte–macrophage colony-stimulating factor (GM-CSF). Previous in vitro or preclinical studies identified an intracellular domain of HER2 (777–789) able of provoking a robust CD8 + cytotoxic T cell response [54, 55]. The immunogenicity of this peptide was attributed to its capacity to induce both HLA class I restricted responses and HLA class II restricted T cell help [56, 57].
The other portion of the AE37 hybrid peptide originates from the MHC Class II invariant chain (Ii), a protein that binds to newly minted MHC Class II molecules in the ER to prevent the binding of peptides destined for presentation by MHC Class I molecules. Only a small portion of Ii (aa 77–80 (LRMK) is needed to regulate the opening of MHC class II peptide binding groove. When the immunogenic HER peptide (AE36) is fused to the Ii (LRMK) peptide, the AE37 vaccine peptide is obtained [33].
For clinical use in the experimental treatment of TNBC patients (e.g. NCT04024800), AE37 will be administered intradermally as a bare peptide in three 21-day cycles for 5 cycles. Pembrolizumab will be given concomitantly with bare peptide, but then extended for an additional 30 cycles.
https://link.springer.com/article/10.1007/s12609-024-00552-3
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