Therapeutic drug for malignant tumors

Abstract

According to the present disclosure there are provided compositions and methods for treating malignant tumors, including an anti-LSR (lipolysis stimulated lipoprotein receptor) antibody that comprises the presently disclosed antibody heavy and light chain complementarity determining region (CDR) sequences, or an antigen-binding fragment thereof, or a functional equivalent thereof. Further provided for treating an LSR-positive malignancy is an LSR antagonist or an LSR inhibitor such as a nucleic acid. Therapeutic administration of the anti-LSR antibody to a subject having an LSR-positive malignant tumor is also described.

1 . A method of treating or preventing a malignant tumor in a subject in need thereof, comprising administering an effective amount of a suppressant of an lipolysis stimulated lipoprotein receptor (LSR) to the subject, wherein the suppressant comprises an anti-LSR antibody or an antigen binding fragment or a functional equivalent thereof,
 wherein the anti-LSR antibody has positions 116-134 and/or 216-230 of SEQ ID NO: 7 as an epitope.   
     
     
         2 . The method of  claim 1 , wherein the malignant tumor is an LSR positive malignant tumor. 
     
     
         3 . The method of  claim 1 , comprising administering the suppressant to the subject wherein the subject is a patient determined to have an episode of LSR positive malignant tumor. 
     
     
         4 . The method of  claim 1 , comprising administering the suppressant to the subject wherein the subject is a patient among malignant tumor patients whose malignant tumor has been determined to be LSR positive malignant tumor. 
     
     
         5 . The method of  claim 1 , wherein the anti-LSR antibody is an antibody having an ability to inhibit exacerbation due to a VLDL. 
     
     
         6 . The method of  claim 1 , wherein the anti-LSR antibody is an antibody selected from a monoclonal antibody, polyclonal antibody, chimeric antibody, humanized antibody, human antibody, multifunctional antibody, bispecific or oligospecific antibody, single chain antibody, scFV, diabody, sc(Fv) 2  (single chain (Fv) 2 ), and scFv-Fc. 
     
     
         7 . The method of  claim 1 , wherein the malignant tumor comprises ovarian cancer or metastasized ovarian cancer. 
     
     
         8 . The method of  claim 7 , wherein the ovarian cancer is recurrent ovarian cancer or early-stage ovarian cancer. 
     
     
         9 . The method of  claim 1 , wherein the malignant tumor comprises ovarian cancer, pancreatic cancer, lung cancer, gastric cancer, or colon cancer. 
     
     
         10 . The method of  claim 7 , wherein the ovarian cancer is ovarian serous adenocarcinoma or ovarian clear cell adenocarcinoma. 
     
     
         11 . The method of  claim 1 , further comprising administering a cell-killing agent. 
     
     
         12 . The method of  claim 1 , wherein the anti-LSR antibody is one or more antibodies selected from the group consisting of:
 (a) an antibody with heavy chain CDRs 1, 2, and 3 and light chain CDRs 1, 2, and 3 comprising amino acid sequences set forth in positions 31-35, 50-66, 99-104, 153-165, 182-188 and 221-230 of SEQ ID NO: 1, respectively;   (b) an antibody with heavy chain CDRs 1, 2, and 3 and light chain CDRs 1, 2, and 3 comprising amino acid sequences set forth in positions 31-35, 50-66, 99-103, 152-165, 182-188 and 221-230 of SEQ ID NO: 2, respectively;   (c) an antibody with heavy chain CDRs 1, 2, and 3 and light chain CDRs 1, 2, and 3 comprising amino acid sequences set forth in positions 31-35, 50-66, 99-104, 153-165, 182-188 and 221-229 of SEQ ID NO: 3, respectively;   (d) an antibody with heavy chain CDRs 1, 2, and 3 and light chain CDRs 1, 2, and 3 comprising amino acid sequences set forth in positions 31-35, 50-66, 99-104, 153-165, 182-188 and 221-229 of SEQ ID NO: 4, respectively;   (e) an antibody with heavy chain CDRs 1, 2, and 3 and light chain CDRs 1, 2, and 3 comprising amino acid sequences set forth in positions 31-35, 50-66, 99-104, 153-165, 182-188 and 221-229 of SEQ ID NO: 5, respectively;   (f) an antibody with heavy chain CDRs 1, 2, and 3 and light chain CDRs 1, 2, and 3 comprising amino acid sequences set forth in positions 31-35, 50-66, 99-104, 153-165, 182-188 and 221-229 of SEQ ID NO: 6, respectively; and   (g) a mutant of the antibody according to any one or more of (a)-(f), which is free of a mutation in the CDRs but comprises one or several substitutions, additions, or deletions in a framework of the antibody in the mutant.