Passive vaccine for elimination of senescent cells

Abstract

Provided herein are immunogenic compositions (vaccines) and methods for immunizing a subject with the immunogenic compositions for inducing an adaptive immune response directed specifically against senescent cells for treatment and prophylaxis of age-related diseases and disorders, and other diseases and disorders associated with or exacerbated by the presence of senescent cells. The immunogenic compositions provided herein comprise at least one or more senescent cell-associated antigens, polynucleotides encoding senescent cell-associated antigens, and recombinant expression vectors comprising the polynucleotides for use in administering to a subject in need thereof.

We claim the following: 
     
         1 . A method of preparing a passive vaccine for administration to a subject who has senescent cells in a tissue that are causing or promoting adverse symptoms,
 wherein the senescent cells are defined as p16 positive cells that are not cancer cells; wherein the method comprises:   (a) obtaining an antibody or antigen binding fragment that contains at least one immunoglobulin variable region that is specific for human p16INK4a protein;   (b) determining an amount of the antibody or antigen binding fragment and a formulation of the antibody or antigen binding fragment with a pharmaceutically acceptable excipient to produce a passive vaccine suitable for human administration that is effective for removing senescent cells from the tissue that are causing or promoting the adverse symptoms; and   (c) compounding the amount of the antibody or antigen binding fragment in the formulation determined in step (b) to produce the passive vaccine.   
     
     
         2 . The method of  claim 1 , wherein the antibody or antigen binding fragment is a human or humanized antibody that is specific for human p16INK4a protein. 
     
     
         3 . The method of  claim 1 , wherein the antibody or antigen binding fragment is an immunoglobulin G. 
     
     
         4 . The method of  claim 1 , further comprising packaging the passive vaccine with an informational insert that describes the use and attendant benefits of the passive vaccine in alleviating at least some of the adverse symptoms. 
     
     
         5 . A method for selectively removing senescent cells from a tissue in a subject that are causing or promoting adverse symptoms,
 wherein the senescent cells are defined as p16 positive cells that are not cancer cells, wherein the method comprises:   obtaining a passive vaccine containing at least one immunoglobulin variable region that is specific for human p16INK4a protein; and   administering the passive vaccine to the subject so as to remove senescent cells from the tissue that are causing or promoting the adverse symptoms;   wherein the passive vaccine has been prepared according to the method of  claim 1 .   
     
     
         6 . The method of  claim 5 , wherein the antibody or antigen binding fragment is a human or humanized antibody that is specific for human p16INK4a protein. 
     
     
         7 . The method of  claim 5 , wherein the antibody or antigen binding fragment is an immunoglobulin G. 
     
     
         8 . The method of  claim 5 , which further comprises monitoring at least one component of a senescence associated secretory phenotype (SASP) in the subject following administration of the passive vaccine. 
     
     
         9 . The method of  claim 5 , which further comprises monitoring the adverse symptoms in the subject following administration of the passive vaccine. 
     
     
         10 . The method of  claim 5 , which further comprises assessing p16 positive cells in the tissue following administration of the passive vaccine. 
     
     
         11 . A unit dose of a pharmaceutical composition configured for administration to a subject who has senescent cells that are causing or promoting adverse symptoms in a tissue of the subject;
 wherein the senescent cells are not cancer cells;   wherein the composition comprises a formulation of an antibody or antigen-binding fragment that contains at least one immunoglobulin variable region that is specific for human p16INK4a protein; and   wherein the amount of the antibody or antigen binding fragment and the formulation of the pharmaceutical composition configure the unit dose to be effective in removing senescent cells that are causing or promoting the adverse symptoms in the tissue.   
     
     
         12 . The unit dose according to  claim 11 , wherein the antibody or antigen binding fragment is a human or humanized antibody that is specific for human p16INK4a protein. 
     
     
         13 . The unit dose according to  claim 11 , wherein the antibody or antigen binding fragment is an immunoglobulin G. 
     
     
         14 . The unit dose according to  claim 11 , packaged with an informational insert that describes the use and attendant benefits of the passive vaccine in alleviating at least some of the adverse symptoms.