Intratumoral vaccination

Abstract

The present disclosure relates to, inter alia, a method for treating a tumor by intratumorally delivering an effective amount of a composition comprising an expression vector that comprises a first nucleotide sequence encoding a secretable vaccine protein, and a second nucleotide sequence encoding a T cell costimulatory fusion protein.

1 . A method for treating a tumor in a subject in need thereof, comprising intratumorally delivering an effective amount of a composition comprising an expression vector that comprises a first nucleotide sequence encoding a secretable qp96-immunoqlobulin (qp96-lq) fusion protein which lacks the qp96 KDEL (SEQ ID NO: 3) sequence, and a second nucleotide sequence encoding a T cell costimulatory fusion protein. 
     
     
         2 . The method of  claim 1 , wherein the intratumoral delivery is in vivo by injection. 
     
     
         3 . The method of  claim 2 , further comprising administering to the subject effective amount of a biological cell comprising an expression vector that comprises a first nucleotide sequence encoding a secretable qp96-lq fusion protein which lacks the qp96 KDEL (SEQ ID NO: 3) sequence, and a second nucleotide sequence encoding a T cell costimulatory fusion protein, wherein the T cell costimulatory fusion protein enhances activation of antigen-specific T cells when administered to the subject. 
     
     
         4 . The method of  claim 1 , wherein the method elicits a potent immune response in a less-immunogenic tumor characterized by reduced inflammation compared to an untreated tumor. 
     
     
         5 . The method of  claim 1 , wherein the method enhances CD4+/CD8+T cell cross-priming to tumor neo-antigens. 
     
     
         6 . The method of  claim 1 , wherein the vector is a mammalian expression vector. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the gp96-Ig fusion protein comprises an Iq portion comprising the Fc region of human IgG1, IgG2, IgG3, IgG4, IgM, IgA, or IgE. 
     
     
         9 . The method of  claim 1 , wherein the T cell costimulatory fusion protein is OX40L-Ig, or a portion thereof that binds to OX40, or ICOSL-Ig, or a portion thereof that binds to ICOS, or 4-1BBL-Ig, or a portion thereof that binds to 4-1BBR, or TL1A-Ig, or a portion thereof that binds to TNFRSF25, or GITRL-Ig, or a portion thereof that binds to GITR, or CD40L-Ig, or a portion thereof that binds to CD40, or CD70-Ig, or a portion thereof that binds to CD27. 
     
     
         10 - 15 . (canceled) 
     
     
         16 . The method of  claim 9 , wherein the T cell costimulatory fusion protein comprises an Ig portion comprising the Fc region of human IgG1, IgG2, IgG3, IgG4, IgM, IgA, or IgE. 
     
     
         17 . The method of  claim 1 , wherein the expression vector comprises DNA or RNA. 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein the expression vector is incorporated into a virus or virus-like particle. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the subject is a human cancer patient. 
     
     
         22 . The method of  claim 21 , wherein delivery increases the activation or proliferation of tumor antigen specific T cells in the patient. 
     
     
         23 . The method of  claim 22 , wherein the activation or proliferation of tumor antigen specific T cells in the patient is increased by at least 25 percent as compared to the level of activation or proliferation of tumor antigen specific T cells in the patient prior to the administration. 
     
     
         24 . The method of  claim 1 , comprising administering in combination with an agent that inhibits immunosuppressive molecules produced by tumor cells. 
     
     
         25 . The method of  claim 24 , wherein the agent that inhibits immunosuppressive molecules is an antibody against PD-1.