Herpes simplex virus expressing foreign genes and method for treating cancers therewith
An anti-cancer pharmaceutical composition includes a herpes simplex virus (HSV) vector into which a nucleic acid sequence encoding for an anti-cancer agent selected from interleukin-12, GM-CSF, and CD has been inserted. A method of treatment of a patient suffering from cancer includes administering to the patient the anti-tumor pharmaceutical composition including a HSV vector having a nucleic acid sequence encoding for an anti-cancer agent selected from interleukin-12, GM-CSF, and CD inserted therein.
1. A method for treating a subject suffering from a central nervous system tumor composed of cells, said method comprising:
administering to the subject a replication competent aneurovirulent γ34.5 deleted herpes simplex virus (HSV) comprising a nucleic acid sequence encoding for interleukin-12, wherein the nucleic acid sequence is inserted within a γ34.5 gene deletion such that the replication competent aneurovirulent herpes simplex virus contains at most two nucleic acid sequences encoding for interleukin-12; and
allowing sufficient time for the HSV to be expressed in a portion of the cells of the tumor and interleukin-12 to exit the portion of cells to contact bystander cells to increase survival time of the subject and thereby treat the subject.
2. The method according to claim 1 , wherein said administering step comprises intratumorally disposing the HSV into the tumor of the subject.
3. The method according to claim 1 , wherein the nucleic acid sequence encoding interleukin-12 (IL-12) comprises subunits p35 and p40 separated by an IRES sequence.
4. A method for treating a subject suffering from a central nervous system tumor composed of cells, said method comprising:
administering to the subject a replication competent aneurovirulent γ34.5 deleted herpes simplex virus (HSV) comprising a nucleic acid sequence encoding for interleukin-12, wherein the nucleic acid sequence is inserted within a γ34.5 gene deletion such that the replication competent aneurovirulent herpes simplex virus contains at most two nucleic acid sequences encoding for interleukin-12; and
allowing sufficient time for the HSV to be expressed in a portion of the cells of the tumor and interleukin-12 to exit the portion of cells to contact bystander cells to increase survival time of the subject and thereby treat the subject wherein the nucleic acid sequence encoding interleukin-12 (IL-12) comprises subunits p35 and p40 separated by an IRES sequence and wherein the IL-12 encoding nucleic acid sequence bicistronically expresses the p35 and p40 subunits to produce self-assembling, heterodimeric IL-12 in the HSV vector.
5. The method according to claim 3 , wherein the nucleic acid sequence encoding interleukin-12 (IL-12) comprises subunits p35 and p40 separated by an IRES sequence wherein the p40 subunit is positioned upstream of the p35 subunit and the IRES.
6. The method according to claim 1 , wherein the HSV is an F strain HSV.