TREATMENT OF CANCER USING RECALL ANTIGENS DELIVERED BY ATTENUATED BACTERIA
Methods, pharmaceutical compositions and vaccines comprising an attenuated bacteria that expresses a recall antigen are disclosed for treatment of cancer.
1 . A method of treating a tumor in a subject, and/or reducing or preventing metastasis of a tumor in a subject, comprising administering to the subject an attenuated bacteria that expresses a recall antigen in an amount effective to treat the tumor, and/or to reduce or prevent metastasis of the tumor.
2 . The method of claim 1 , wherein the bacteria is one or more of Listeria monocytogenes, Salmonella thyphimurium, Vibrio cholera, Clostridium , and Bifidobacterium breve.
3 . The method of claim 1 , wherein the bacteria is Listeria monocytogenes.
4 . The method of claim 1 , wherein the recall antigen is an epitope of one or more of tetanus toxoid, measle virus, and polio virus.
5 . The method of claim 1 , wherein the recall antigen is an epitope of tetanus toxoid.
6 . The method of claim 1 , wherein the tumor is a tumor of one or more of the pancreas, ovary, uterus, neck, head, breast, prostate, liver, lung, kidney, neurones, glia, colon, testicle, or bladder.
7 . The method of claim 1 , wherein the tumor is an inoperable tumor.
8 . The method of claim 1 , wherein prior to administration to the subject, the bacteria are cultured in yeast medium.
9 . The method of claim 1 , which further comprises administering CpG to the subject.
10 . The method of claim 1 , wherein prior to administration of bacteria to the subject, the subject is screened for their major histocompatibility complex (WIC) 1 haplotype and administered an antigen for which the subject shows a CD8 T cell recall response.
11 . The method of claim 1 , wherein prior to administration of bacteria to the subject, an epitope of the antigen is administered to the subject to generate memory T cells to the antigen.
12 . The method of claim 1 , wherein bacteria are administered systemically to the subject.
13 . The method of claim 1 , wherein bacteria are administered by direct injection to a tumor site in the subject.
14 . The method of claim 1 , wherein bacteria are administered in myeloid-derived suppressor cells (MDSCs).
15 . The method of claim 1 , further comprising administering to the subject a chemotherapeutic agent that reduces the number of myeloid-derived suppressor cells (MDSCs).
16 . The method of claim 15 , wherein the chemotherapeutic agent is gemcitabine.
17 . The method of claim 1 , wherein the subject is a human.
18 . The method of claim 1 , wherein the subject is a mammal.
19 . The method of claim 1 , wherein the method is effective to reduce tumor growth and/or size.
20 . The method of claim 1 , wherein the method is effective to reduce metastases.