Patent EP-3906942-A1 (EP)
Inventor: HONJO TASUKU
IPC: A61P35/00
Filed: 2019-11-28
Abstract: A marker for judging the efficacy of therapy with a PD-1 signal inhibitor-containing drug before or at an early stage of the therapy is provided. As biomarkers for predicting or judging the efficacy of therapy with a PD-1 signal inhibitor-containing drug, the following (i) and/or (ii) is used. 
(i) at least one metabolite in serum and/or plasma selected from the group consisting of alanine, 4-cresol, cysteine, hippuric acid, oleic acid, indoxyl sulfate, ribose, indoleacetate, uric acid, trans-urocanic acid, pipecolic acid, N-acetylglucosamine, indolelactic acid, arabinose, arabitol, cystine, indoxyl sulfate, gluconic acid, citrulline, creatinine, N-acetylaspartic acid, pyroglutamic acid, trimethyllysine, asy-dimethylarginine, sym-dimethylarginine, methylhistidine, acylcarnitine, 3-aminoisobutyric acid, acetylcarnosine, arginine, N-acetylornitine, 3-hydroxyisovaleric acid, pyruvic acid, α-ketoglutaric acid, GSSG, 2-hydrobutyric acid, 1,5-anhydro-D-sorbitol, glutamine, glycine, lysine, taurine, AMP, acetylcarnosine, 3-hydroxybutyric acid, 2-hydroxyisovaleric acid, acetoacetic acid, tryptophan, 2-hydroxyglutaric acid, malic acid, quinolinic acid, caproic acid, isoleucine, GSH and 3-OH-kynurenine 
(ii) at least one cellular marker in peripheral blood selected from the group consisting of the frequency of CD4 +  T cells among peripheral blood mononuclear cells (% of CD4 +  T cells among PBMC), the frequency of CD8 +  T cells among peripheral blood mononuclear cells (% of CD8 +  T cells among PBMC), the frequency of naive T cells among CD8 +  T cells (% of Tnaive among CD8 +  T cells), the frequency of central memory T cells among CD4 +  T cells (% of Tcm among CD4 +  T cells), the frequency of central memory T cells among CD8 +  T cells (% of Tcm among CD8 +  T cells), the frequency of effector memory T cells among CD8 +  T cells (% of Tem among CD8 +  T cells), the frequency of terminally differentiated effector memory T cells among CD4 +  T cells (% of Temra among CD4 +  T cells), the frequency of terminally differentiated effector memory T cells among CD8 +  T cells (% of Temra among CD8 +  T cells), the ratio of mitochondrial activation status in CD8 +  T cells to mitochondrial activation status in CD4 +  T cells [e.g., the ratio of mitochondrial reactive oxygen species production in CD8 +  T cells to mitochondrial reactive oxygen species production in CD4 +  T cells (Mito SOX CD8/CD4), the ratio of mitochondrial mass in CD8 +  T cells to mitochondrial mass in CD4 +  T cells (Mito mass CD8/CD4)], PGC-la and PGC-1β expression in CD8 +  T cells (PGC-1αβ (MF1) of CD8 +  T cells), the frequency of PD-1 highly expressing CD8 +  T cell population (% of PD-1 high  among CD8 +  T cells), the frequency of FoxP3 lowly expressing CD45RA +  T cell population among CD4 +  T cells (% of FoxP3 low  CD45RA +  among CD4 +  T cells), the frequency of T-bet highly expressing T cell population among CD4 +  T cells (% of T-bet high  among CD4 +  T cells), the frequency of T-bet lowly expressing T cell population among CD4 +  T cells (% of T-bet low  among CD4 +  T cells), the frequency of T-bet expressing T cell population among CD8 +  T cells (% of T-bet +  among CD8 +  T cells) and the frequency of T-bet and EOMES expressing T cell population among CD8 +  T cells (% of T-bet +  EOMES +  among CD8 +  T cells).