Method of indirect immunization of human ovarian cancer patients through selection of xenogeneic immunoglobulin fc portions

Abstract

The present document describes a method for therapeutic indirect immunization of an optimally debulked human ovarian cancer patient having a CA125 antigen level in the blood above normal levels, comprising administering to said human patient a monoclonal antibody specific to CA125 antigen having at least a xenogeneic Fc region; an immune complex formed between CA125 antigen and said monoclonal antibody having at least a xenogeneic Fc region; or a combination thereof.

1 . A method for therapeutic indirect immunization of an optimally debulked human ovarian cancer patient having a CA125 antigen level in the blood above normal levels, comprising administering to the human patient:
 (a) a monoclonal antibody specific to CA125 antigen having at least a xenogeneic Fc region;   (b) an immune complex formed between CA125 antigen and the monoclonal antibody having at least a xenogeneic Fc region; or   (c) a combination thereof.   
     
     
         2 . The method of  claim 1 , wherein the CA125 antigen level in the blood above normal levels is more than 35 units/mL of CA125 antigen in the blood. 
     
     
         3 . The method of  claim 1 , wherein the CA125 antigen level in the blood above normal levels is at least 50 units/mL of CA125 antigen in the blood. 
     
     
         4 . The method of  claim 1 , wherein the xenogeneic Fc region is from an IgA, IgD, IgG, or IgM isotype. 
     
     
         5 . The method of  claim 1 , wherein the xenogeneic Fc region is from an IgG isotype. 
     
     
         6 . The method of  claim 5 , wherein the IgG isotype is an IgG1 isotype. 
     
     
         7 . The method of  claim 1 , wherein the xenogeneic Fc region is a murine Fc region, a rat Fc region, a rabbit Fc region, a goat Fc region, or a hamster Fc region. 
     
     
         8 - 10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein the antibody specific to CA125 is mAb-B43.13 (oregovomab). 
     
     
         12 . The method of  claim 1 , wherein administering is one, two, three, or a maximum of four administrations. 
     
     
         13 . The method of  claim 1 , further comprising administration of an immune adjuvant. 
     
     
         14 . The method of  claim 13 , wherein the immune adjuvant is a chemotherapeutic agent, an immunostimulatory compound, an immune homeostatic checkpoint inhibitor, or a combination thereof. 
     
     
         15 . The method of  claim 14 , wherein the chemotherapeutic agent is a platinum-based chemotherapy, taxol, doxorubicin, topotecan, a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, or combinations thereof,
 wherein the immunostimulatory compound is a TLR3 agonist, a TLR4 agonist, or combinations thereof, and   wherein the immune homeostatic checkpoint inhibitor is an anti-PD-L1 antibody, an anti-CTLA-4 antibody, and anti-PD-1 antibody, or combinations thereof.   
     
     
         16 . The method of  claim 15 , wherein the platinum-based chemotherapy comprises cisplatin, carboplatin, oxaliplatin, nedaplatin, triplatin tetranitrate, phenanthriplatin, picoplatin, satraplatin, and combinations thereof. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 15 , wherein the TLR3 agonist is polyIC, polylCLC (Hiltonol®). 
     
     
         19 . The method of  claim 14 , wherein the chemotherapeutic agent is a combination of carboplatin and taxol. 
     
     
         20 . The method of  claim 14 , wherein the therapeutic monoclonal antibody specific for a tumor associated antigen is mAb-B43.13 (oregovomab), and the chemotherapeutic agent is a combination of carboplatin and taxol. 
     
     
         21 . (canceled) 
     
     
         22 . The method of  claim 15 , wherein the anti-PD-L1 antibody is selected from the group consisting of B7-H1 antibody, BMS-936559 antibody, MPDL3280A (atezolizumab) antibody, MEDI-4736 antibody, MSB0010718C antibody or combinations thereof,
 wherein the anti-CTLA-4 antibody is selected from the group consisting of ipilimumab or tremelimumab or combinations thereof,   wherein the anti-PD-1 antibody is selected from the group consisting of Nivolumab antibody, pembrolizumab antibody, pidilizumab antibody or combinations thereof, and AMP-224, and   wherein the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor is selected from the group consisting of olaparib, niraparib, rucaparib, talazoparib, veliparib, CEP 9722, E7016, and BGB-290, or combinations thereof.   
     
     
         23 - 25 . (canceled) 
     
     
         26 . The method of  claim 1 , wherein a dose of the monoclonal antibody specific to CA125 antigen having at least a xenogeneic Fc region is from about 0.1 to about 10 mg. 
     
     
         27 . The method of  claim 1 , wherein the method is for the treatment of ovarian cancer. 
     
     
         28 . The method of  claim 1 , wherein the therapeutic indirect immunization is inducing a mannose receptor dependent immune response in the human patient. 
     
     
         29 - 112 . (canceled)