Vaccines for the treatment of cancer and compositions for enhancing vaccine efficacy

Abstract

The present invention relates to the treatment and prevention of cancer. The present invention relates to vaccines comprising solubilized components of cancer cells or cancer-associated cells. Moreover, the present invention also relates to methods of producing vaccines from biological samples comprising cancer cells or cancer-associated cells and using said vaccines for the treatment or prevention of cancer in subjects. The present invention also relates to methods of producing vaccines, in particular, autologous vaccines. The present invention also relates to therapeutic uses of mesenchymal stem cells and to methods of treatment and or prevention that comprise administering mesenchymal stem cells to a subject. The present invention also relates to methods of enhancing the efficacy of vaccines and methods for the treatment and prevention of cancer, and to compositions and kits suitable for use in the methods.

1 . A method of stimulating an immune response to an antigen, the method comprising administering to a subject in need thereof a composition comprising said antigen and a composition comprising mesenchymal stem cells (MSCs), wherein said MSCs are not genetically modified. 
     
     
         2 . The method of  claim 1 , wherein the composition comprising said antigen is a vaccine for a disease or disorder afflicting said subject or to which said subject is susceptible. 
     
     
         3 . The method of  claim 1 , wherein said MCSs originate from adipose tissue or bone marrow. 
     
     
         4 . The method of  claim 1 , wherein said MSCs originate from the subject intended to be administered said antigen and said MSCs. 
     
     
         5 . The method of  claim 1 , wherein said antigen and said MSCs are co-formulated in a single composition. 
     
     
         6 . The method of  claim 1 , wherein said antigen is a bacterial antigen. 
     
     
         7 . The method of  claim 1 , wherein the composition comprising said antigen is an anti-cancer vaccine. 
     
     
         8 . The method of  claim 9 , wherein the anti-cancer vaccine comprises solubilised components of a cancer cell or a cancer-associated cell. 
     
     
         9 . The method of  claim 9 , wherein the anti-cancer vaccine comprises solubilised and reduced components of a cancer cell or a cancer-associated cell, and streptavidin, avidin, or neutravidin, or a fragment or variant of any thereof capable of binding a mammalian protein. 
     
     
         10 . The method of  claim 7 , wherein the anti-cancer vaccine is a vaccine prepared according to a method comprising:
 (i) exposing a biological sample comprising at least one cancer cell or cancer-associated cell to an ionic detergent, a reducing agent, and streptavidin or a fragment or variant thereof having the capability of binding a mammalian protein, to produce a composition comprising a solubilized biological sample comprising components from said cancer cell or cancer-associated cell and streptavidin or a fragment or variant thereof having the capability of binding a mammalian protein, solvent precipitating said composition, followed by resuspension of the resulting precipitate in a suitable liquid, wherein said vaccine comprises said resuspended precipitate; or   (ii) a) exposing a biological sample comprising at least one cancer cell or cancer-associated cell to an ionic detergent in a suitable liquid to produce a solubilized biological sample comprising soluble material and insoluble material;
 b) partitioning the soluble and insoluble material of the solubilized biological sample to produce a soluble fraction and an insoluble fraction; 
 c) exposing the soluble fraction to a reducing agent; 
 d) exposing the soluble fraction to streptavidin or a fragment or variant thereof having the capability of binding a mammalian protein; 
 e) performing a solvent precipitation of the soluble fraction; and 
 f) resuspending the precipitate in a suitable liquid; 
   wherein said vaccine comprises said resuspended precipitate; or   (iii) a) exposing a biological sample comprising at least one cancer cell or cancer-associated cell to an ionic detergent and a reducing agent in a suitable liquid to produce a solubilized biological sample comprising soluble material and insoluble material;
 b) partitioning the soluble and insoluble material of the solubilized biological sample to produce a soluble fraction and an insoluble fraction; 
 c) exposing the soluble fraction to streptavidin or a fragment or variant thereof having the capability of binding a mammalian protein; 
 d) performing a solvent precipitation of the soluble fraction; and 
 e) resuspending the precipitate in a suitable liquid; 
   wherein said vaccine comprises said resuspended precipitate.   
     
     
         11 . The method of  claim 10 , wherein the biological sample is from the subject intended to receive the vaccine. 
     
     
         12 . A composition comprising a vaccine and mesenchymal stem cells (MSCs), wherein said MSCs are not genetically modified and wherein said vaccine comprises an antigen. 
     
     
         13 . The composition of  claim 12 , wherein the MCSs originate from adipose tissue or bone marrow. 
     
     
         14 . The composition of  claim 12 , wherein the MSCs originate from the subject intended to be administered the antigen and the MSCs. 
     
     
         15 . The composition of  claim 12 , wherein the antigen is an antigen of an infectious agent. 
     
     
         16 . The composition of  claim 15 , wherein the antigen is a bacterial antigen. 
     
     
         17 . The composition of  claim 12 , wherein the composition comprising said antigen is an anti-cancer vaccine. 
     
     
         18 . The composition of  claim 17 , wherein the anti-cancer vaccine comprises solubilised components of a cancer cell or cancer-associated cell. 
     
     
         19 . The composition of  claim 17 , wherein the anti-cancer vaccine comprises solubilised and reduced components of a cancer cell or cancer-associated cell, and streptavidin, avidin, or neutravidin, or a fragment or variant of any thereof capable of binding a mammalian protein. 
     
     
         20 . A method for the treatment or prevention of cancer in a human subject, the method comprising the steps of:
 (i) obtaining a biological sample comprising at least one cancer cell or cancer-associated cell from said subject, exposing the biological sample to an ionic detergent, a reducing agent, and a non-mammalian polypeptide capable of binding a mammalian protein, to produce an anti-cancer vaccine comprising a solubilized biological sample comprising components from said cancer cell or cancer-associated cell, and a non-mammalian polypeptide capable of binding a mammalian protein wherein said mammalian polypeptide comprises an RGD or RGD-like motif, and administering a therapeutically effective amount of said vaccine to said subject; and   (ii) obtaining a biological sample comprising MSCs from said subject, isolating MSCs from the biological sample and preparing a composition comprising MSCs, and administering a therapeutically effective amount of said composition comprising MSCs to said subject, wherein said MSCs are not genetically modified;   wherein all steps of the method are performed by or under the supervision of a registered medical practitioner having prime responsibility for the clinical care of said subject throughout said method.