Combinations and methods for treating neoplasms

1. A combination, comprising:

a) an oxidizing agent or a reducing agent;

b) a protein denaturing agent; and

c) a hapten;

wherein said combination is formulated for injectable delivery into a neoplasm of a mammal.

2. A kit, comprising the combination of claim 1 .

3. An article of manufacture, comprising:

a) packaging material;

b) a combination comprising:

i) an oxidizing agent or a reducing agent;

ii) a protein denaturing agent; and

iii) a hapten selected from the group consisting of trinitrophenol (TNP), dinitrophenol (DNP), N-iodoacetyl-N′-(5-sulfonic 1-naphthyl) ethylene diamine (AED), and dinitrofluorobenzene(DNFB); and

c) a label indicating that the article is for treating neoplasms.

4. A method for treating neoplasm in a mammal, comprising in situ administering to neoplasm of a mammal an effective amount of (1) a hapten, and (2) coagulation agent(s) or treatment(s) that causes coagulation of the neoplasm, whereby an autologous immune response is generated against the neoplasm and the neoplasm is treated;

wherein the hapten and coagulation agent(s) are administered to the neoplasm via injection or in combination with a surgical procedure; and

wherein the hapten is selected from the group consisting of trinitrophenol (TNP), dinitrophenol (DNP), N-iodoacetyl-N′-(5-sulfonic 1-naphthyl) ethylene diamine (AED), and dinitrofluorobenzene(DNFB).

5. The method of claim 4 , wherein the coagulation agent(s) is selected from the group consisting of:

a) an oxidizing agent or a reducing agent; and

b) an oxidizing agent or a reducing agent, and a protein denaturing agent.

6. The method of claim 5 , wherein the oxidizing or reducing agent, the protein denaturing agent and the hapten are formulated in a single pharmaceutical composition or each is formulated in a separate pharmaceutical composition.

7. The method of claim 5 , wherein the oxidizing agent is selected from the group consisting of hydrogen peroxide (H 2 O 2 ), ozone, NaIO 4 , potassium peroxymonosulfate (oxone), D,L-S-methyllipoic acid methyl ester, tertiary butyl hydroperoxide, carbamide peroxide, menadione, diamide, iodogen, N-bromosuccinimide, omeprazole and N-ethylmaleimide.

8. The method of claim 5 , wherein the protein denaturing agent is selected from the group consisting of an alcohol, guanidine hydrochloride, guanidinium thiocyanate, sodium citrate, 2-mercaptoethanol, sarcosyl, phenol, chloroform and urea.

9. The method of claim 5 , wherein the method further comprises in situ administering to neoplasm of a mammal an effective amount of an anti-neoplasm agent.

10. The method of claim 9 , wherein the anti-neoplasm agent is selected from the group consisting of an alkylating agent, an antimetabolite, a natural product, a platinum coordination complex, an anthracenedione, a substituted urea, a methylhydrazine derivative, Mitotane (o,p′-DDD), a hormone and an antagonist.

11. The method of claim 5 , wherein the oxidizing agent is H 2 O 2 , the protein denaturing agent is ethanol and the hapten is DNP.

12. The method of claim 5 , wherein the oxidizing agent or reducing agent is from about 0.01% (w/w) to about 35% (w/w), the protein denaturing agent is from about 1% (w/w) to about 99% (w/w) and the hapten is from about 1 mg/ml to about 80 mg/ml.

13. The combination of claim 1 , wherein the hapten is selected from the group consisting of trinitrophenol (TNP), dinitrophenol (DNP), N-iodoacetyl-N′-(5-sulfonic 1-naphthyl) ethylene diamine (AED), and dinitrofluorobenzene(DNFB).

14. The combination of claim 1 , wherein the oxidizing or reducing agent, the protein denaturing agent and the hapten are formulated in a single pharmaceutical composition or each is formulated in a separate pharmaceutical composition.

15. The combination of claim 1 , wherein the oxidizing agent is selected from the group consisting of hydrogen peroxide (H 2 O 2 ), ozone, NaIO 4 , potassium peroxymonosulfate (oxone), D,L-S-methyllipoic acid methyl ester, tertiary butyl hydroperoxide, carbamide peroxide, menadione, diamide, iodogen, N-bromosuccinimide, omeprazole and N-ethylmaleimide.

16. The combination of claim 1 , wherein the protein denaturing agent is selected from the group consisting of an alcohol, guanidine hydrochloride, guanidinium thiocyanate, sodium citrate, 2-mercaptoethanol, sarcosyl, phenol, chloroform and urea.

17. The combination of claim 1 , wherein the combination further comprises an anti-neoplasm agent.

18. The combination of claim 17 , wherein the anti-neoplasm agent is selected from the group consisting of an alkylating agent, an antimetabolite, a natural product, a platinum coordination complex, an anthracenedione, a substituted urea, a methylhydrazine derivative, Mitotane (o,p′-DDD), a hormone and an antagonist.

19. The combination of claim 1 , wherein the oxidizing agent is H 2 O 2 , the protein denaturing agent is ethanol and the hapten is DNP.

20. The combination of claim 1 , wherein the oxidizing agent or reducing agent is from about 0.01% (w/w) to about 35% (w/w), the protein denaturing agent is from about 1% (w/w) to about 99% (w/w) and the hapten is from about 1 mg/ml to about 80 mg/ml.

21. The method of claim 4 , wherein the coagulation comprises carbamide peroxide and/or a chitosan.

22. The method of claim 21 , wherein the chitosan is a chitosan oligosaccharide or a water soluble chitosan.

23. The method of claim 22 , wherein the hapten is selected from the group consisting of trinitrophenol (TNP), dinitrophenol (DNP), N-iodoacetyl-N′-(5-sulfonic 1-naphtyl) ethylene diamine (AED), and dinitrofluorobenzene(DNFB).

24. The method of claim 5 , wherein the oxidizing agent is carbamide peroxide, the protein denaturing agent is ethanol and the hapten is DNP.

25. The combination of claim 1 , wherein the oxidizing agent is carbamide peroxide, the protein denaturing agent is ethanol and the hapten is DNP.

26. The method of claim 4 , wherein the mammal is a human.