Edible plant exosome-like nanovectors for vaccination

Abstract

Provided are compositions and methods for using the same. In some embodiments, the compositions include an EPELN encapsulating and/or having associated therewith an active agent and a plasma membrane derived from a tumor and/or cancer cell coating the EPELN. In some embodiments, the active agent is a therapeutic agent or an immune response modifier, and in some embodiments the plasma membrane has one or more tumor-associated and/or cancer-associated antigens. Also provided are methods for using the compositions for treating tumors and/or cancers, inducing anti-tumor and/or anti-cancer immune responses, activating antigen-presenting cells, targeting CD1 lc dendritic cells, and preventing or reducing metastasis.

What is claimed is: 
     
         1 . A composition comprising:
 an edible-plant derived exosome-like nanoparticle (EPELN) encapsulating and/or having associated therewith an active agent selected from the group consisting of a therapeutic agent and an immune response modifier; and   a plasma membrane derived from a tumor and/or cancer cell coating the EPELN, wherein the plasma membrane comprises one or more tumor-associated and/or cancer-associated antigens.   
     
     
         2 . The composition of  claim 1 , wherein the immune response modifier comprises an miRNA, optionally wherein the miRNA is selected from the group consisting of miR18a (5′-UAAGGUGCAUCUAGUGCAGAUAG-3′; SEQ ID NO: 1) and miR17 (5′-CAAAGUGCUUACAGUGCAGGUAG-3′; SEQ ID NO: 2). 
     
     
         3 . The composition of any one of the preceding claims, wherein the plasma membrane comprises one or more tumor-associated antigens. 
     
     
         4 . The composition of any one of the preceding claims, wherein the edible plant is a mushroom. 
     
     
         5 . The composition of any one of the preceding claims, wherein the therapeutic agent is selected from a phytochemical agent, an immune-response inducing and/or enhancing agent, and a chemotherapeutic agent. 
     
     
         6 . The composition of any one of the preceding claims, wherein the therapeutic agent is a phytochemical agent, optionally wherein the phytochemical agent is selected from curcumin, resveratrol, baicalein, equol, fisetin, and quercetin. 
     
     
         7 . The composition of any one of the preceding claims, wherein the therapeutic agent is a chemotherapeutic agent, optionally wherein the chemotherapeutic agent is selected from the group consisting of retinoic acid, 5-fluorouracil, vincristine, actinomycin D, adriamycin, cisplatin, docetaxel, doxorubicin, and taxol. 
     
     
         8 . The composition of any one of the preceding claims, wherein the therapeutic agent comprises a nucleic acid molecule selected from the group consisting of an siRNA, a microRNA, and a mammalian expression vector. 
     
     
         9 . A pharmaceutical composition comprising a pharmaceutically-acceptable vehicle, carrier, and/or excipient and the composition of any one of the preceding claims, optionally wherein the pharmaceutical composition is pharmaceutically acceptable for use in a human. 
     
     
         10 . A method for treating a tumor and/or a cancer, the method comprising administering to a subject in need thereof an effective amount of a composition, the composition comprising:
 (i) an edible-plant derived exosome-like nanoparticle (EPELN) encapsulating and/or having associated therewith an active agent selected from the group consisting of a therapeutic agent and an immune response modifier; and   (ii) a plasma membrane derived from a tumor and/or cancer cell coating the EPELN, wherein the plasma membrane comprises one or more tumor-associated and/or cancer-associated antigens.   
     
     
         11 . A method for treating a tumor and/or a cancer in a subject, the method comprising:
 (a) providing an edible-plant derived exosome-like nanoparticle (EPELN) encapsulating and/or having associated therewith an active agent selected from the group consisting of a therapeutic agent and an immune response modifier;   (b) coating the EPELN with a plasma membrane derived from a tumor and/or a cancer cell isolated from the subject to produce a therapeutic composition; and   (c) administering an effective amount of the therapeutic composition to the subject,   
       whereby the therapeutic composition induces an immune response in the subject against a tumor-associated and/or cancer-associated antigen to thereby treat the tumor and/or the cancer in the subject. 
     
     
         12 . The method of any one of  claims 10  and  11 , wherein the tumor cell and/or cancer cell is autologous to the subject 
     
     
         13 . A method for inducing an anti-tumor and/or an anti-cancer immune response in a subject, the method comprising administering to the subject an effective amount of the composition of any one of  claims 1 - 8 , whereby an anti-tumor and/or anti-cancer immune response is induced in the subject to at least one tumor-associated and/or cancer-associated antigen present in the composition. 
     
     
         14 . A method for activating antigen-presenting cells (APCs) in a subject, the method comprising administering to the subject an effective amount of the composition of any one of  claims 1 - 8 , whereby APCs present in the subject are activated against at least one tumor-associated and/or cancer-associated antigen present in the subject. 
     
     
         15 . A method for targeting a CD11c dendritic cell present in or isolated from a subject, the method comprising contacting the CD11c dendritic cell with a composition of any one of  claims 1 - 8 . 
     
     
         16 . A method for preventing or reducing metastasis of a cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of a composition of any one of  claims 1 - 8 . 
     
     
         17 . The method of any one of  claims 10 - 16 , wherein the composition is administered orally or intravenously. 
     
     
         18 . The method of any one of  claims 10 - 17 , wherein administering the composition induces an immune response in the subject to at least one tumor-associated and/or cancer-associated antigen present in the composition. 
     
     
         19 . The method of any one of  claims 10 - 18 , wherein the EPELN is derived from a mushroom. 
     
     
         20 . The method of any one of  claims 10 - 19 , wherein the immune response modifier comprises an miRNA, optionally miR18a (5′-UAAGGUGCAUCUAGUGCAGAUAG-3′; SEQ ID NO: 1). 
     
     
         21 . The method of any one of  claims 10 - 20 , wherein the therapeutic agent is selected from a phytochemical agent and a chemotherapeutic agent. 
     
     
         22 . The method of any one of  claims 10 - 21 , wherein the therapeutic agent is a phytochemical agent, and wherein the phytochemical agent is selected from curcumin, resveratrol, baicalein, equol, fisetin, and quercetin. 
     
     
         23 . The method of any one of  claims 10 - 22 , wherein the therapeutic agent is a chemotherapeutic agent selected from the group consisting of retinoic acid, 5-fluorouracil, vincristine, actinomycin D, adriamycin, cisplatin, docetaxel, doxorubicin, and taxol. 
     
     
         24 . The method of any one of  claims 10 - 23 , wherein the therapeutic agent comprises a nucleic acid molecule selected from an siRNA, a microRNA, and a mammalian expression vector. 
     
     
         25 . A method for activating an antigen-presenting cell (APC) in a subject against a tumor cell and/or a cancer cell, the method comprising administering to the subject an effective amount of a composition comprising:
 (i) an edible-plant derived exosome-like nanoparticle (EPELN) encapsulating and/or having associated therewith an active agent selected from the group consisting of a therapeutic agent and an immune response modifier; and   (ii) a plasma membrane derived from a tumor and/or cancer cell coating the EPELN, wherein the plasma membrane comprises one or more tumor-associated and/or cancer-associated antigens   whereby an antigen-presenting cell (APC) in a subject is activated against the tumor cell and/or the cancer cell.