METHODS OF SYNERGISTIC TREATMENT OF CANCER
A method of treating cancer includes administering a dose of a chemotherapy agent in combination with a dose of a composition consisting essentially of attenuated Salmonella typhimurium . The dose of the chemotherapy agent is lower than a maximum effective dose of the chemotherapy agent. The combination provides a synergistic reduction in tumor burden when compared to the reduction in tumor burden provided by administration of an equivalent dose of the chemotherapy agent without the composition consisting essentially of attenuated Salmonella typhimurium.
1 . An anti-tumor agent for treating cancer, comprising:
a combination of a dose of a chemotherapy agent and a dose of attenuated Salmonella typhimurium containing a plasmid carrying a coding sequence encoding a human interleukin-2, wherein the human interleukin-2 consists of the amino acid sequence shown in SEQ ID NO: 2,
wherein the chemotherapy agent comprises one or more of doxorubicin, carboplatin, cyclophosphamide, daunorubicin, oxaliplatin, 5-fluorouracil, or gemcitabine,
wherein the combination provides a synergistic reduction in tumor burden when compared to the reduction in tumor burden provided by administration of an equivalent dose of the chemotherapy agent without the attenuated Salmonella typhimurium containing the plasmid carrying the coding sequence encoding the human interleukin-2, and
wherein the toxicity of the combination is lower than the toxicity of the maximum tolerated dose of the chemotherapy agent.
2 . The anti-tumor agent of claim 1 , wherein the dose of the chemotherapy agent is 25% of the maximum tolerated dose of the chemotherapy agent.
3 . The anti-tumor agent of claim 1 , wherein the dose of attenuated Salmonella typhimurium containing the plasmid carrying the coding sequence encoding the human interleukin-2 is 1×10 9 colony forming units.
4 . The anti-tumor agent of claim 1 , wherein the attenuated Salmonella typhimurium containing the plasmid carrying the coding sequence encoding the human interleukin-2 is administered orally.
5 . The anti-tumor agent of claim 1 , wherein a first dose of the chemotherapy agent and the dose of the attenuated Salmonella typhimurium containing the plasmid carrying the coding sequence encoding the human interleukin-2 are administered on a first day.
6 . The anti-tumor agent of claim 5 , wherein a second dose of the chemotherapy agent is administered on a second day a week after the first day.
7 . The anti-tumor agent of claim 6 , wherein a third dose of the chemotherapy agent is administered on a third day a week after the second day.
8 . The anti-tumor of claim 5 , wherein a plurality of doses of the chemotherapy agent and a plurality of doses of the attenuated Salmonella typhimurium are administered on a plurality of days after the first day.
9 . A method of treating cancer, the method comprising:
administering a combination of a dose of a chemotherapy agent and a dose of attenuated Salmonella typhimurium containing a plasmid carrying a coding sequence encoding a human interleukin-2, wherein the human interleukin-2 consists of the amino acid sequence shown in SEQ ID NO: 2,
wherein the chemotherapy agent comprises one or more of doxorubicin, carboplatin, cyclophosphamide, daunorubicin, oxaliplatin, 5-fluorouracil, or gemcitabine,
wherein the combination provides a synergistic reduction in tumor burden when compared to the reduction in tumor burden provided by administration of an equivalent dose of the chemotherapy agent without the attenuated Salmonella typhimurium containing the plasmid carrying the coding sequence encoding the human interleukin-2, and
wherein the toxicity of the combination is lower than the toxicity of the maximum tolerated dose of the chemotherapy agent.
10 . The method of claim 9 , wherein the dose of the chemotherapy agent is 25% of the maximum tolerated dose of the chemotherapy agent.
11 . The method of claim 9 , wherein the dose of attenuated Salmonella typhimurium containing the plasmid carrying the coding sequence encoding the human interleukin-2 is 1×10 9 colony forming units.
12 . The method of claim 9 , wherein the attenuated Salmonella typhimurium containing the plasmid carrying the coding sequence encoding the human interleukin-2 is administered orally.
13 . The method of claim 9 , wherein a first dose of the chemotherapy agent and the dose of the attenuated Salmonella typhimurium containing the plasmid carrying the coding sequence encoding the human interleukin-2 are administered on a first day.
14 . The method of claim 13 , wherein a second dose of the chemotherapy agent is administered on a second day a week after the first day.
15 . The method of claim 14 , wherein a third dose of the chemotherapy agent is administered on a third day a week after the second day.
16 . The method of claim 13 , wherein a plurality of doses of the chemotherapy agent and a plurality of doses of the attenuated Salmonella typhimurium are administered on a plurality of days after the first day.