Ganglioside gm3-containing nanoparticles as immunomodulators

Abstract

The present invention describes a pharmaceutical composition whose active ingredient includes conjugates of membrane vesicles of Neisseria meningitidis and the GM3 ganglioside in a conjugation ratio in excess of proteins, has particular characteristics of size, surface charge and a morphology associated with nano-particulate systems that give it advantageous properties as an immunomodulator, because it induces a convenient and significant reduction of myeloid-derived suppressor cells that has an impact on the response of T lymphocytes and on the survival of patients with tumors. The invention further discloses the use of the pharmaceutical composition disclosed in the treatment of cancer, particularly those cancers where the myeloid-derived suppressor cells (MDSCs) are high; as well as a method of treatment with said composition in cancer patients and a method to select those who will receive said treatment.

We claim: 
     
         1 - 8 . (canceled) 
     
     
         9 . A method for treating a subject in need thereof comprising the administration of a pharmaceutical composition comprising nanoparticles characterized by hydrophobic conjugation of outer membrane protein complex (OMPC) of  Neisseria meningitidis  bacterium to a GM3 ganglioside, wherein the OMPC:GM3 ganglioside conjugation ratio ranges from 1.5:1 to 10:1. 
     
     
         10 . The method of  claim 9 , wherein the nanoparticles are characterized by a monomodal distribution of volume in a range from 15 to p25 nm particle size, polydispersity index of 0.230, and/or negative Z potential with nominal value in the range from 25 to 45 mV. 
     
     
         11 . The method of  claim 9 , wherein the composition treats cancer. 
     
     
         12 . The method of  claim 11 , wherein the cancer is melanoma, prostate cancer, head and neck, ovary, bladder, hepatocellular carcinoma, non-small cell lung cancer, chronic lymphocytic leukemia, squamous cell carcinoma of the esophagus, Hodgkin's lymphoma, renal carcinoma, or mammary carcinoma. 
     
     
         13 . The method of  claim 9 , wherein the pharmaceutical composition is administered via SC, intradermal, intramuscular, intratumoral routes or by direct application to mucosal surfaces. 
     
     
         14 . The method of  claim 9 , wherein the pharmaceutical composition is administered with a weekly frequency for at least a total of four doses. 
     
     
         15 . The method of  claim 14 , wherein the pharmaceutical composition is administered subsequently fortnightly or monthly in maintenance doses for at least six months. 
     
     
         16 . The method of  claim 9 , wherein the pharmaceutical composition is administered in a dose of 100 μg to 2 mg. 
     
     
         17 . The method of  claim 16 , wherein the pharmaceutical composition is administered in a dose of 200 μg to 1200 μg.