PLATFORM ONCOLYTIC VECTOR FOR SYSTEMIC DELIVERY

1 .- 206 . (canceled)

207 . An oncolytic virus comprising a mutation or a deletion or a partial deletion of the viral gene K7R, and further comprising at least one of:

(a) an exogenous nucleic acid that codes for a cytokine, or a functional domain or a fragment or a variant thereof;

(b) an exogenous nucleic acid that codes for a cytokine receptor, or a functional domain or a fragment or a variant thereof;

(c) an exogenous nucleic acid that codes for a chemokine, or a functional domain, or a fragment or a variant thereof; or

(d) any combination of (a)-(c).

208 . The oncolytic virus of claim 207 , comprising the exogenous nucleic acid that codes for the chemokine, or a functional domain or a fragment or a variant thereof, wherein the chemokine, or a functional domain or a fragment or a variant thereof comprises at least one of: CCL5, ITAC (CXCL11), a fractalkine, or a functional domain or a fragment or a variant thereof.

209 . The oncolytic virus of claim 207 , comprising the exogenous nucleic acid that codes for the cytokine, or a functional domain or a fragment or a variant thereof, wherein the cytokine, or a functional domain or a fragment or a variant thereof comprises IL15, IL7, or a functional domain or a fragment or a variant thereof.

210 . The oncolytic virus of claim 207 , comprising the exogenous nucleic acid that codes for the cytokine receptor, or a functional domain or a fragment or a variant thereof, wherein the cytokine receptor, or a functional domain or a fragment or a variant thereof comprises IL15 receptor alpha, or a functional domain or a fragment or a variant thereof.

211 . The oncolytic virus of claim 207 , further comprising an exogenous nucleic acid that codes for at least one of: HMGB1, PIAS3, LIGHT, or a functional domain or a fragment or a variant thereof.

212 . The oncolytic virus of claim 207 , further comprising at least one of: an exogenous nucleic acid that codes for a chemokine receptor, or a functional domain or a fragment or a variant thereof; a mutation or a deletion or a partial deletion of viral gene A52R; and an exogenous nucleic acid that codes for a protein, or a functional domain or a fragment or a variant thereof, that enhances degradation of an extracellular matrix (ECM) of a tumor; or any combination thereof.

213 . The oncolytic virus of claim 212 , comprising the exogenous nucleic acid that codes for a protein, or a functional domain or a fragment or a variant thereof, that enhances degradation of an extracellular matrix (ECM) of a tumor, wherein the protein, or a functional domain or a fragment or a variant thereof, that enhances degradation of the ECM of a tumor comprises at least one of: a membrane associated protein that is capable of degrading hyaluronan, or a microbial protein that is capable of degrading hyaluronan.

214 . The oncolytic virus of claim 213 , comprising the membrane associated protein that is capable of degrading hyaluronan, wherein the membrane associated protein that is capable of degrading hyaluronan comprises a membrane associated hyaluronidase.

215 . The oncolytic virus of claim 214 , wherein the membrane associated hyaluronidase is PH-20.

216 . The oncolytic virus of claim 213 , comprising the microbial protein that is capable of degrading hyaluronan, wherein the microbial protein comprises a secreted hyaluronidase.

217 . The oncolytic virus of claim 216 , wherein the secreted hyaluronidase is selected from the group consisting of: HysA, lin, sko, and rv, or any combination thereof.

218 . The oncolytic virus of claim 217 , wherein the secreted hyaluronidase comprises the HysA.

219 . The oncolytic virus of claim 213 , comprising the microbial protein that is capable of degrading hyaluronan, wherein the microbial protein comprises hyaluronidase protein HysA from Loxosceles intermedia.

220 . The oncolytic virus of claim 207 , further comprising a modification in the genome of the virus, wherein the modification enhances production of an enveloped extracellular form (EEV) of the virus.

221 . The oncolytic virus of claim 212 , comprising the exogenous nucleic acid that codes for the chemokine receptor, or a functional domain or a fragment or a variant thereof, wherein the chemokine receptor comprises at least one of: a CXC receptor, a CC receptor, a CX3C receptor, and a XC receptor, or a functional domain or a fragment or a variant thereof.

222 . The oncolytic virus of claim 221 , wherein the chemokine receptor comprises a least one of: CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7, CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CX3CR1, XCR1, or a functional domain or a fragment or a variant thereof.

223 . The oncolytic virus of claim 222 , wherein the chemokine receptor comprises CXCR4 or CCR2, or a functional domain or a fragment or a variant thereof.

224 . The oncolytic virus of claim 207 , further comprising a modification in the genome of the virus.

225 . The oncolytic virus of claim 207 , further comprising a mutation or a deletion or a partial deletion of a viral gene selected from the group consisting of: F13L, A36R, A34R, B5R, A33R, B8R, B18R, SPI-1, SPI-2, B15R, VGF, E3L, K3L, A41L, N1L.

226 . The oncolytic virus of claim 207 , wherein the oncolytic virus comprises a poxvirus, an adeno associated virus, an adenovirus, a reovirus, a lentivirus, a herpes simplex virus, a vesicular stomatitis virus, a mengovirus, or a myxomavir.

227 . The oncolytic virus of claim 226 , wherein the oncolytic virus comprises the poxvirus, and wherein the poxvirus comprises a vaccinia virus.

228 . The oncolytic virus of claim 227 , wherein the vaccinia virus comprises a Western Reserve vaccinia virus.

229 . The oncolytic virus of claim 207 , wherein the viral genome comprises the thymidine kinase gene or the viral genome comprises a mutation or a deletion or a partial deletion of the thymidine kinase gene.

230 . An oncolytic virus comprising an exogenous nucleic acid that codes for IL15 and IL15-Rα, or a functional domain or a fragment or a variant thereof.

231 . An oncolytic virus comprises an exogenous nucleic acid that codes for IL15 and IL15-Rα, or a functional domain or a fragment or a variant thereof, wherein the virus further comprises a mutation or a deletion or a partial deletion of the viral gene K7R.

232 . A method of treating a cancer, the method comprising administering to a subject an oncolytic virus according to claim 207 .