Cancer treatment with 237 car-t cell based therapeutics recognizing the tn epitope
AssigneesThe University of Chicago, The Board of Trustees of the University of Illinois
InventorsHans SCHREIBER, David KRANZ, Karin SCHREIBER, Yanran HE, Preeti SHARMA
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Abstract
The disclosure provides Tn epitope-specific chimeric antigen receptors and scFvs, including soluble scFvs and multimeric scFvs, as well as methods of identifying cancer subjects and cancer subject sub-populations amenable to anti-Tn immunotherapy and methods of treating cancer.
Claims83
A chimeric antigen receptor (CAR) that specifically binds a Tn glycopeptide comprising:
- (a) a single chain variable fragment (scFv) that specifically binds a Tn glycopeptide, wherein the scFv comprises a heavy chain complementarity determining region 1 (CDRH1) sequence at positions 150-159 of SEQ ID NO:19, a CDRH2 sequence at positions 177-186 of SEQ ID NO:19, a CDRH3 sequence at positions 227-232 of SEQ ID NO:19, a light chain complementarity determining region 1 (CDRL1) at positions 26-37 of SEQ ID NO:19, a CDRL2 at positions 55-57 of SEQ ID NO:19, and a variant of the CDRL3 sequence at positions 96-100 of SEQ ID NO:19 comprising at least one amino acid variation from the wild-type antibody 237 light chain complementarity determining region 3 sequence at positions 96-100 of SEQ ID NO:19;
- and
- (b) a T-cell signaling domain.
A soluble cancer-specific 237 single chain variable fragment (scFv) that specifically binds a Tn glycopeptide comprising a heavy chain complementarity determining region 1 (CDRH1) sequence at positions 150-159 of SEQ ID NO:19, a CDRH2 sequence at positions 177-186 of SEQ ID NO:19, a CDRH3 sequence at positions 227-232 of SEQ ID NO:19, a light chain complementarity determining region 1 (CDRL1) at positions 26-37 of SEQ ID NO:19, a CDRL2 at positions 55-57 of SEQ ID NO:19, and a variant of the CDRL3 sequence at positions 96-100 of SEQ ID NO:19 comprising at least one amino acid variation from the wild-type antibody 237 light chain complementarity determining region 3 sequence at positions 96-100 of SEQ ID NO:19.
A method of identifying a subject as a cancer patient amenable to anti-Tn epitope cancer therapy comprising
- (a) determining if there is a mutation in the cosmc gene of the subject;
- and
- (b) identifying the subject as a cancer patient amenable to anti-Tn epitope cancer therapy if the subject harbors a mutant cosmc gene.
A method of identifying a subject as a cancer patient amenable to anti-Tn epitope cancer therapy comprising
- (a) obtaining a biological sample from a subject;
- (b) determining the level of core 1 β3-Gal-T-specific molecular chaperone (COSMC) and/or T-Synthase in the sample;
- (c) comparing the level of COSMC and/or T-Synthase in the sample to a control;
- and
- (d) identifying the subject as a cancer patient amenable to anti-Tn epitope cancer therapy if the level of COSMC and/or T-Synthase is lower in the sample of the subject than in the control.
Dependencies are inferred from the claim text.