Improved phox2b pc-car generation based on structure and saturation mutagenesis
AssigneeThe Children's Hospital of Philadelphia
InventorNikolaos SGOURAKIS
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Abstract
The neuroblastoma immunopeptidome is enriched with peptides derived from proteins essential for tumorigenesis including the unmutated peptide QYNPIRTTF (SEQ ID NO: 1) discovered on HLA-A*24:02 which is derived from the neuroblastoma dependency gene and master transcriptional regulator PHOX2B. To target QYNPIRTTF, a saturation mutagenesis screen of the scFV CDR loops of a previously developed peptide-centric chimeric antigen receptors (PC-CARs) was performed to identify improved immunotherapeutics targeting of the neuroblastoma CRC master regulator PHOX2B. Also provided are methods of screening for cross-reactivity of a candidate peptide:HLA targeted therapeutic against off-target HLAs.
Claims24
A method of screening for cross-reactivity of a candidate peptide:HLA targeted therapeutic against off-target HLAs, the method comprising the steps of:
- (a) contacting an antigen-binding portion of the candidate peptide:HLA targeted therapeutic with a composition comprising human leukocyte antigens linked to a solid substrate, and (b) detecting binding of the antigen-binding portion of the candidate peptide:HLA targeted therapeutic to the solid substrate, wherein binding of the antigen-binding portion of the candidate peptide:HLA targeted therapeutic to the solid substrate is indicative of a cross-reactivity specific for said native human leukocyte antigens.
18-20. (canceled)
Dependencies are inferred from the claim text.