IgG generated against benign tumor-associated antigens prevented the effects of 1,2-dimethylhydrazine in rats.
We showed the possibility of significant decreasing of the frequency of chemically induced colon cancer in rats by vaccination with polyclonal rabbit IgG generated against purified tumor-associated antigens (TAA). TAA were isolated from benign rat colon tumors by the method developed in our laboratory (Zusman et al 1994) using affinity chromatography columns with gel fiberglass membranes (R. Zusman, 1992) containing anti-tumor IgG. The IgG was isolated from rabbits following their vaccination with TAA. Sprague Dawley rats were vaccinated with anti-TAA IgG (100 micrograms/rat) suspended in Freunds adjuvant by weekly subcutaneous injections for 5 weeks. The induction of colon cancer was caused by weekly injections with 1,2-dimethylhydrazine (DMH) (20 mg/kg) for 7 weeks and was started one week after the end of the vaccination. The results of experiments were evaluated 6 months after the start of cancer induction. IgG protected against the carcinogenic effects of DMH. The number of tumor-bearing rats decreased to 64% as compared with 90% in the control group. In vaccinated rats, the incidence of tumors was almost 3 times less than of control, i.e. 3.6 and 9.3, respectively. The number of malignant tumors was also significantly smaller in vaccinated rats than in controls, being 24% and 58%, respectively. Metastases were found only in controls, 4 of 30 rats. The results of our experiments have shown that anti-TAA IgG not only has anti-tumor effects but also prevents the malignization of benign tumors. As one of the main components of TAA which was isolated from colon cancer rats was soluble p53 antigen (Zusman et al 1994), we suggest that the vaccine which has been generated in our experiments may be regarded as acting mainly against p53 antigen, and its antitumor effects should also be considered as effects of p53 antibodies. The further studies will be performed to clarify this.
Zusman
I
I
Laboratory of Teratology & Experimental Oncology, Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel.
Zusman
R
R
Karol
D
D
Gurevich
P
P
D019813:1,2-Dimethylhydrazine; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004127:Dimethylhydrazines; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use*; D016233:Immunotherapy, Active; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D000951:Antigens, Neoplasm; D002273:Carcinogens; D004127:Dimethylhydrazines; D007074:Immunoglobulin G; D019813:1,2-Dimethylhydrazine