TARGETED CANCER THERAPY
Some embodiments of the present disclosure are directed to methods that include delivering to a subject a nucleic acid encoding an antigen, wherein the nucleic acid is delivered via a tumor-selective vehicle or via intratumoral injection, and delivering to the subject an immune cell expressing a receptor that binds to the antigen.
1 . A method of expressing CD19 on the surface of a tumor cell in a subject, the method comprising
(i) contacting the tumor cell with a tumor-selective vehicle comprising a nucleic acid encoding an antigen, wherein the wherein the antigen comprises and epitope of CD19, and
(ii) administering to the subject an immune cell expressing a chimeric antigen receptor that binds to the antigen wherein the immune cell binds to the expressed antigen, thereby resulting in killing of the tumor.
2 .- 9 . (canceled)
10 . The method of claim 1 , wherein the antigen is selected from full length CD19, a fragment of CD19, at least one C2 Ig-like domain of CD19, or a linear epitope of CD19.
11 . The method of claim 1 , wherein the nucleic acid encoding the antigen is encapsulated within the tumor-selective vehicle.
12 . The method of claim 1 , wherein tumor-selective vehicle is a virus or a pseudovirus.
13 . The method of claim 12 , wherein the tumor-selective vehicle is an oncolytic virus.
14 . The method of claim 13 , wherein the oncolytic virus is an adenovirus, a vaccinia virus, a Sindbis virus, a Seneca valley virus, a Coxsackie virus, a measles virus, a reovirus, a vaccinia virus, a Newcastle disease virus, a vesicular stomatitis virus, a herpes simplex virus, a poliovirus, or a parvovirus.
15 . The method of claim 12 , wherein the tumor-selective vehicle is a chimeric virus.
16 . The method of claim 15 , wherein the chimeric virus is obtained from engineering adeno-associated viruses and bacteriophages that display tumor selective peptides.
17 . (canceled)
18 . The method of claim 12 , wherein the tumor-selective vehicle is an adeno-associated virus (AAV) that is modified to target tumor cells.
19 . The method of claim 12 , wherein the tumor-selective vehicle is a human papillomavirus, a human papillomavirus, a non-human papillomavirus, or a modified non-human papillomavirus.
20 .- 23 . (canceled)
24 . The method of claim 12 , wherein the tumor-selective vehicle is a pseudovirus.
25 . The method of claim 11 , wherein tumor-selective vehicle is or comprises a natural polymer, a synthetic polymer, a cationic peptide, a cell-penetrating peptide, a biodegradable nanoparticle, a liposome, a lipoplex, a polyplex, a micelle, a dendrimer, a gel, a mucoadhesive or a silicon nanoneedle.
26 . (canceled)
27 . The method of claim 1 , wherein the nucleic acid encoding an antigen is a deoxyribonucleic acid (DNA).
28 . The method of claim 1 , wherein the nucleic acid encoding an antigen is a ribonucleic acid (RNA).
29 . The method of claim 28 , wherein the RNA is a messenger RNA (mRNA).
30 .- 32 . (canceled)
33 . The method of claim 1 , wherein the immune cell is a T cell, a B cell, an NK cell, a dendritic cell, or an NKT cell.
34 .- 37 . (canceled)
38 . The method of claim 1 , wherein the tumor-selective vehicle is delivered via a parenteral, enteric or topical route.
39 .- 41 . (canceled)
42 . A method comprising
delivering to a subject an engineered nucleic acid that induces expression of a self-antigen, wherein the engineered nucleic acid is delivered via a tumor-selective vehicle or via intratumoral injection, and
delivering to the subject an immune cell expressing a receptor that binds to the self-antigen.
43 .- 85 . (canceled)
86 . A method comprising
delivering to a tumor two nucleic acids each encoding a different antigen, or delivering to a tumor two nucleic acids each inducing expression of a different self-antigen; and
delivering to the tumor an immune cell expressing a bispecific antigen receptor that binds to the two different antigens.
87 .- 92 . (canceled)