Patent TW-202043773-A (TW)
Title: Prediction and/or determination marker for effectiveness of treatment with drug containing pd-1 signal inhibitor
Inventor: HONJO TASUKU
IPC: A61K39/395
Filed: 2019-11-29
Abstract: Provided is a marker for distinguishing the effectiveness of disease treatment with a drug containing a PD-1 signal inhibitor prior to said treatment or at an early stage of the treatment. (i) and/or (ii) indicated below is used as a biomarker for predicting or determining the effectiveness of treatment with a drug containing a PD-1 signal inhibitor. (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, indoxyle sulfate, gluconic acid, citrulline, creatinine, N-acetylaspartic acid, pyroglutamic acid, trimethyllysine, asy-dimethylarginine, sym-dimethylarginine, methylhistidine, acyl carnitine, 3-aminoisobutyric acid, acethykcarnosine, arginine, N-acetylornithine, 3-hydroxyisovaleric acid, pyruvic acid, [alpha]-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 cell marker in peripheral blood selected from the group consisting of the frequency of CD4+ T cells among peripheral blood mononuclear cells (PBMC) (% of CD4+ T cells among PBMC), the frequency of CD8+ T cells among peripheral blood mononuclear cells (PBMC) (% 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 the mitochondrial activation status of CD8+ T cells to the mitochondrial activation status of CD4+ T cells (for example, the ratio (Mito SOX CD8/CD4) of the mitochondrial reactive oxygen expression amount of CD8+ T cells to the mitochondrial reactive oxygen expression amount of CD4+ T cells or the ratio (Mito mass CD8/CD4) of the mitochondrial volume (mass) of CD8+ T cells to the mitochondrial volume of CD4+ T cells), the expression of PGC-1[alpha] and PGC-1[beta] of CD8+ T cells (PGC-1[alpha][beta](MFI) of CD8+ T cells), the frequency of CD8+ T cell populations with high expression of PD-1 (% of PD-1high among CD8+ T cells), the frequency of CD45RA+ T cell populations with low expression of FoxP3 among CD4+ T cells (% of FoxP3low CD45RA+ among CD4+ T cells), the frequency of T cell populations with high expression of T-bet among CD4+ T cells (% of T-bethigh among CD4+ T cells), the frequency of T cell populations with low expression of T-bet among CD4+ T cells (% of T-betlow among CD4+ T cells), the frequency of T cell populations in which T-bet is expressed among CD8+ T cells (% of T-bet+ among CD8+ T cells), and the frequency of T cell populations in which T-bet and EOMES are expressed among CD8+ T cells (% of T-bet+ EOMES+ among CD8+ T cells).