Conditional superagonist CTL ligands for the promotion of tumor-specific CTL responses

摘要

What is described is a novel genetic screen, involving recombinant technology and class I antigen cross-presentation, to search for supraoptimal superagonists of the 27L MART-1 mutant selecting for single amino acid substitution mutants of 27L that activate human antigen-specific CTL clones recognizing the wild-type MART-126-35 epitope. Three novel mutant epitopes are identified with superagonist properties that are functionally superior to 27L. The ability of a given analog to act as superagonist varies among patients. Also described is the use of methods to establish panels of potential superagonist APLs to individualize tumor peptide vaccines among patients. The methodology is replicated to identify APL to NY-ESO-1157-165 and NY-ESO-1157-170 tumor epitopes. A general method is described that is useful to produce a tumor vaccine to any tumor epitope.

主权项

1. A compound for the treatment of a patient with a tumor, wherein the compound comprises a peptide comprising a tumor epitope, wherein the tumor epitope comprises an amino acid substitution in a tumor antigen, wherein the tumor antigen is SEQ ID NO: 144 or 228, and wherein the compound comprises a sequence selected from the group consisting of SEQ ID NOS: 362-365 and 368-376.