Modulation of stimulatory and non-stimulatory myeloid cells

Abstract

Provided herein are methods and compositions for enhancing an immune response and/or for the treatment of an immune-related condition in an individual, e.g., cancer, comprising killing, disabling, or depleting non-stimulatory myeloid cells using an antigen binding protein such as an antibody or antigen binding fragment thereof.

1 .- 88 . (canceled) 
     
     
         89 . A method for treating a cancer in a subject being treated with an anti-Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) antibody or antigen-binding fragment thereof, comprising administering at least one of pembromizulab, nivolumab, or ipilimumab to the subject. 
     
     
         90 . The method of  claim 89 , comprising administering pembromizulab to the subject. 
     
     
         91 . The method of  claim 89 , comprising administering nivolumab to the subject. 
     
     
         92 . The method of  claim 89 , comprising administering ipilimumab to the subject. 
     
     
         93 . The method of  claim 89 , wherein the cancer tissue is a solid cancer or a liquid cancer. 
     
     
         94 . The method of  claim 89 , wherein the cancer is selected from the group consisting of: melanoma, kidney, hepatobiliary, head-neck squamous carcinoma, pancreatic, colon, bladder, glioblastoma, prostate, lung, and breast. 
     
     
         95 . The method of  claim 89 , wherein the pembromizulab, nivolumab, or ipilimumab is administered concurrently with the anti-TREM2 antibody or antigen-binding fragment thereof. 
     
     
         96 . The method of  claim 89 , wherein the pembromizulab, nivolumab, or ipilimumab is administered subsequently to the anti-TREM2 antibody or antigen-binding fragment thereof. 
     
     
         97 . The method of  claim 89 , wherein the subject has previously received an immunotherapy. 
     
     
         98 . The method of  claim 97 , wherein the immunotherapy comprises at least one of pembromizulab, nivolumab, or ipilimumab. 
     
     
         99 . The method of  claim 89 , wherein the anti-TREM2 antibody or antigen-binding fragment is at least one of a monoclonal antibody, an IgG1 antibody, an IgG4 antibody, an afucosylated antibody, a human antibody, a humanized antibody, a chimeric antibody, and a full length antibody. 
     
     
         100 . The method of  claim 89 , wherein the anti-TREM2 antibody or antigen-binding fragment thereof comprises a human Fc domain. 
     
     
         101 . The method of  claim 89 , wherein the anti-TREM2 antibody or antigen-binding fragment thereof comprises a human IgG1 Fc domain. 
     
     
         102 . The method of  claim 89 , wherein the anti-TREM2 antibody or antigen-binding fragment thereof is an afucosylated antibody. 
     
     
         103 . The method of  claim 89 , wherein the anti-TREM2 antibody or antigen-binding fragment thereof is a humanized antibody. 
     
     
         104 . The method of  claim 89 , wherein the anti-TREM2 antibody or antigen-binding fragment thereof is present in an amount effective to kill, disable, or deplete a TREM2+ myeloid cell via antibody-dependent cell-mediated cytotoxicity activity, antibody-dependent phagocytosis activity, complement-dependent cytotoxicity activity, or antibody-mediated phagocytosis activity. 
     
     
         105 . The method of  claim 89 , further comprising determining the presence of TREM2+ myeloid cells from a cancer sample obtained from the subject. 
     
     
         106 . The method of  claim 105 , wherein the cancer sample is obtained by needle biopsy, punch biopsy, or surgical excision. 
     
     
         107 . The method of  claim 105 , wherein the determining step comprises determining the presence of TREM2 mRNA expression or TREM2 protein expression. 
     
     
         108 . The method of  claim 105 , wherein the determining step is carried out using at least one of polymerase chain reaction (PCR), quantitative PCR (qPCR), RT-qPCR, microarray, gene array, RNAseq, and a cell sorting method.