Anti-galectin antibody biomarkers predictive of anti-immune checkpoint and anti-angiogenesis responses

Abstract

The present invention is based on the identification of novel biomarkers predictive of responsiveness to a combination of anti-immune checkpoint and anti-angiogenesis therapies.

1 - 8 . (canceled) 
     
     
         9 . A method of assessing the efficacy of an agent for treating a cancer in a subject that is unlikely to be responsive to anti-immune checkpoint and anti-angiogenesis combination therapy, comprising:
 a) detecting the amount or activity of at least one antibody that specifically binds a biomarker listed in Table 1, or antigen-binding fragment thereof, from a subject in which the agent has not been administered;   b) detecting the amount or activity of at least one antibody that specifically binds the biomarker listed in Table 1, or antigen-binding fragment thereof, in the subject in which the agent has been administered; and   c) comparing the amount or activity of the at least one antibody that specifically binds the biomarker listed in Table 1, or antigen-binding fragment thereof, from steps a) and b), wherein a significantly increased amount or activity of the at least one antibody that specifically binds the biomarker listed in Table 1, or antigen-binding fragment thereof, in step b) relative to step a), indicates that the agent treats the cancer in the subject.   
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 9 , wherein between the first point in time and the subsequent point in time, the subject has undergone treatment, completed treatment, and/or is in remission for the cancer. 
     
     
         12 . The method of  claim 9 , wherein the first and/or at least one subsequent sample is selected from the group consisting of ex vivo and in vivo samples. 
     
     
         13 . The method of  claim 9 , wherein the first and/or at least one subsequent sample is obtained from an animal model of the cancer. 
     
     
         14 . The method of  claim 9 , wherein the first and/or at least one subsequent sample is a portion of a single sample or pooled samples obtained from the subject. 
     
     
         15 - 16 . (canceled) 
     
     
         17 . The method or assay of  claim 9 , wherein the subject sample and/or the control sample has not been contacted with either a) any anti-cancer treatment, b) any anti-immune checkpoint agent, or c) any anti-angiogenesis agent. 
     
     
         18 . The method or assay of  claim 9 , wherein the subject has not been administered any either a) any anti-cancer treatment, b) any anti-immune checkpoint agent, or c) any anti-angiogenesis agent. 
     
     
         19 . The method or assay of  claim 9 , further comprising recommending, prescribing, or administering at least one additional anti-cancer therapeutic agent, optionally wherein the at least one additional anti-cancer therapeutic agent is an anti-immune checkpoint agent, ipilimumab, an anti-angiogenesis agent, an anti-VEGF agent, bevacizumab, a neutralizing anti-Gal-1 antibody or antigen-binding fragment thereof, a neutralizing anti-Gal-3 antibody or antigen-binding fragment thereof, a neutralizing anti-Gal-9 antibody or antigen-binding fragment thereof, or combinations thereof. 
     
     
         20 . The method or assay of  claim 9 , wherein the subject sample is selected from the group consisting of serum, whole blood, plasma, urine, cells, cell lines, and biopsies. 
     
     
         21 . The method or assay of  claim 9 , wherein the amount of the least one antibody that specifically binds a biomarker listed in Table 1, or antigen-binding fragment thereof. 
     
     
         22 . The method or assay of  claim 21 , wherein the reagent is selected from the group consisting of a Gal-1 polypeptide or fragment thereof, Gal-3 polypeptide or fragment thereof, Gal-9 polypeptide or fragment thereof, or any combination thereof. 
     
     
         23 . The method or assay of  claim 9 , wherein the at least one antibody that specifically binds a biomarker listed in Table 1, or antigen-binding fragment thereof, is assessed by enzyme-linked immunosorbent assay (ELISA), radioimmune assay (RIA), immunochemically, Western blot, or flow cytometry. 
     
     
         24 . The method or assay of  claim 23 , wherein the biomarker listed in Table 1 is immobilized onto a solid support. 
     
     
         25 . The method or assay of  claim 24 , wherein the solid support is an array, bead, or plate. 
     
     
         26 . The method or assay of  claim 9 , wherein the at least one antibody that specifically binds a biomarker listed in Table 1, or antigen-binding fragment thereof, is detected by detecting binding of an anti-IgG antibody against the antibody or antigen-binding fragment thereof. 
     
     
         27 . The method or assay of  claim 9 , wherein the at least one antibody that specifically binds the biomarker listed in Table 1, or antigen-binding fragment thereof, is an anti-human Gal-1, an anti-human Gal-3, or an anti-human Gal-9 antibody, or an antigen-binding fragment thereof, optionally wherein the antibody or antigen-binding fragment thereof is a neutralizing antibody or neutralizing antigen-binding fragment thereof. 
     
     
         28 . The method or assay of  claim 9 , wherein the anti-immune checkpoint and anti-angiogenesis combination therapy comprises at least one antibody selected from the group consisting of anti-CTLA-4 antibodies, anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, anti-VEGF antibodies, and combinations thereof. 
     
     
         29 . The method or assay of  claim 28 , wherein the anti-immune checkpoint therapy comprises ipilimumab and/or anti-angiogenesis therapy comprises bevacizumab. 
     
     
         30 . The method or assay of  claim 9 , wherein the likelihood of the cancer in the subject to be responsive to anti-immune checkpoint and anti-angiogenesis combination therapy is the likelihood of at least one criteria selected from the group consisting of cellular proliferation, tumor burden, m-stage, metastasis, progressive disease, clinical benefit rate, survival until mortality, pathological complete response, semi-quantitative measures of pathologic response, clinical complete remission, clinical partial remission, clinical stable disease, recurrence-free survival, metastasis free survival, disease free survival, circulating tumor cell decrease, circulating marker response, and RECIST criteria. 
     
     
         31 . The method or assay of  claim 9 , wherein the cancer is a solid tumor. 
     
     
         32 . The method or assay of  claim 9 , wherein the cancer is melanoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), bladder cancer, prostate cancer, metastatic hormone-refractory prostate cancer, renal cell cancer, colon cancer, ovarian cancer, or brain glioblastoma multiforme. 
     
     
         33 . The method or assay of  claim 32 , wherein the melanoma is metastatic melanoma. 
     
     
         34 . The method or assay of  claim 9 , wherein the subject is a mammal. 
     
     
         35 . The method or assay of  claim 34 , wherein the mammal is an animal model of cancer. 
     
     
         36 . The method or assay of  claim 34 , wherein the mammal is a human.