ONCOLYTIC VIRUS COMBINED WITH CAR T CELLS FOR ANTI-TUMOR THERAPY
The present disclosure provides methods of treating cancer using complementary transgenic oncolytic viruses and genetically engineered CAR T cells. In one embodiment, the oncolytic virus comprises nucleotide sequences encoding CD19, or CD19 and IL-12, and the genetically engineered T cells express a chimeric antigen receptor that recognizes CD19.
1 . A method of treatment of an individual having a cancer, comprising the steps of:
administering to the individual an oncolytic virus comprising nucleotide sequences encoding an antigen, or an antigen and IL-12; and
administering to the individual genetically engineered T cells expressing a chimeric antigen receptor (CAR) that recognizes the antigen.
2 . The method of claim 1 , wherein the antigen is CD19.
3 . The method of claim 2 , wherein the CD19 antigen comprises the amino acid sequence of SEQ ID NO: 5, 6 or 7.
4 . The method of claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 10.
5 . The method of claim 1 , wherein the T cells are obtained from an individual autologously or allogeneically.
6 . The method of claim 1 , wherein the oncolytic virus comprises M protein comprising one or more amino acid mutations of N32S, N49D, M51R, H54Y V221F, V225I and S226R as compared with SEQ ID NO. 1.
7 . The method of claim 6 , wherein the M protein comprises the amino acid sequence of SEQ ID NO:2.
8 . The method of claim 1 , wherein the oncolytic virus comprises G protein comprising one or more amino acid mutations V53I, A141V, D172Y, K217E, D232G, V331A, V371E, G436D, T438S, F453L, T471I, and Y487I.
9 . The method of claim 8 , wherein the G protein comprises the amino acid sequence of SEQ ID NO: 4.
10 . The method of claim 1 , wherein the oncolytic virus is vesicular stomatitis virus (VSV).
11 . The method of claim 1 , wherein the oncolytic virus is administered parenterally or intratumorally.
12 . The method of claim 11 , wherein the oncolytic virus is administered intravenously, subcutaneously or intramuscularly
13 . The method of claim 1 , wherein the engineered T cells are administered via intravenous, intra-arterial, or intralymphatic delivery.
14 . The method of claim 1 , wherein the individual is further treated with surgery, immunotherapy, chemotherapy, radiation therapy, targeted therapy, hormone therapy, stem cell therapies, or blood transfusions.
15 . The method of claim 1 , wherein the cancer is acute lymphoblastic leukemia, acute B-lymphocytic leukemia, chronic non-lymphocytic leukemia, or non-Hodgkin's lymphoma.