Precision medicine by targeting PD-L1 variants for treatment of cancer

摘要

The invention relates to human targets of interest (TOI), anti-TOI ligands, kits compositions and method.

主权项

1. A method of treating a solid tumor; melanoma; renal cell carcinoma; non small-cell lung cancer; bladder cancer; Hodgkin's lymphoma; or gastric cancer in a human, the method comprising administering to said human an anti-PD-L1 antibody or antibody fragment that specifically binds to a human PD-L1 that is expressed by a PD-L1 nucleotide sequence comprising a variation selected from the group consisting of:
rs1411262; rs4143815; 8923C; rs150439231; rs138261640; rs142983488; rs76741468; rs822336; rs183400620; rs187252832; rs146143976; rs139023765; rs73641615; rs17718883; rs139709512; rs140045210; rs141978642; rs146495642; rs370800260; rs143235887; rs373692552; rs140304675; rs12551333; rs376993991; rs367921713; rs41280721; rs61752860;wherein the antibody or antibody fragment that specifically binds to human PD-L1 comprises a human gamma-1 heavy chain constant region that comprises an amino acid selected from the group consisting of:
an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42; andwherein said human comprises:(i) an IGHG1*01 human heavy chain constant region gene segment, or the human expresses antibodies comprising human gamma-1 heavy chain constant regions comprising said selected amino acid; and(ii) a PD-L1 nucleotide sequence comprising said selected variation.