Vaccines against dangerous infections and cancer

Reflection & Reaction Vaccines against dangerous infections and cancer Last year, the Journal of the National Cancer Institute (2001) published an interesting article entitled, “Anthrax is a cancer drug?” This paper showed that anthrax toxins can inhibit tumour growth in nude mice, and in some cases, cause tumour regression.1 During the last 15 years, my research group has studied the influence of rodent immunisation with tularemia and anthrax live vaccines (TLV and ALV) on mutagenesis, carcinogenesis, and tumour growth. Both vaccines are widely used for immunisation of people and animals against tularemia and anthrax in Russia and the former countries of the Soviet Union. In the former USSR, about 12 million people were immunised annually with TLV and between 1941 and 1976, 267 million people received the vaccine.2 In Russia, about 60 000 people each year are newly immunised with ALV and 100 000 are reimmunised. Both infections are extremely dangerous for humans; a fact that was poignantly illustrated last year following the events of September 11th when anthrax was used as a biological weapon by a terrorist organisation. Interestingly, both the tularemia infection process and the vaccination process are similar in rats and humans. We have shown that the chromosomal aberration (CA) and micronuclei (MN) incidence induced by certain chemical, biological, and physical carcinogens and mutagens, are significantly decreased in the bone-marrow cells of rats, mice, guinea pigs, and Armenian (grey) hamsters immunised with TLV.3–5 But TLV on its own does not induce chromosomal aberrations.3,4 We have seen that preimmunisation of rats with TLV decreases the incidence of chemically-induced tumours, prolongs the mean latency period, and reduces tumour mass.6,7 Immunisation also decreases the growth of transplantable tumours. It is noteworthy, that intratumoral injection of TLV also causes a decrease in neoplastic growth and, in some cases, total destruction of the tumour.3 Mechanistically, TLV seems to decrease the activity of cytochrome P450, which is needed for metabolic activation of promutagens

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and is involved in DNA repair activity.3,5 In addition, immunisation of tumourbearing rodents with TLV significantly increases the efficacy of radiation therapy and chemotherapy. We have given TLV as an adjuvant to cancer treatment of patients with corpus uteri and lung cancer admitted to the Cancer Research Centre in Yerevan, Armenia. The mean life span of 54 patients immunised with TLV before radiotherapy or chemotherapy increased significantly compared with patients who did not receive TLV.8 We have also investigated the use of ALV (live attenuated spores of anthrax produced in Armenia primarily for veterinary practice). ALV vaccine is non-clastogenic and does not induce chromosomal aberrations or micronuclei in the bone marrow of rats and mice immunised with a dose equivalent to that used for sheep immunisation.9,10 Also, the clastogenic action of various chemotherapeutic agents is substantially reduced in immunised rodents. As seen with TLV immunisation, a decrease in the clastogenic action of promutagens also occurs. In one experiment, we studied the influence of ALV immunisation on the carcinogenic action of 7,12-dimethylbenz(a)anthracene in rats. The carcinogen was injected 15 days after immunisation, and rodents were sacrificed 6 months later. We observed a significant reduction in both tumour incidence and the mass of any lesions that occured.9,10 In addition, the mean latency period of tumour development was longer. Consistently, we have also seen that the incidence and growth of transplantable tumours can be reduced by ALV preimmunisation. Some of our experiments have used an ALV produced in Russia (known as the STI vaccine) which is intended for human immunisation. Similar results have been obtained. This particular vaccine formulation was developed in 1943 by Ginsburg and co-workers and was so-called because it was made at the Sanitary Technical Institute. By 1945, about 1 million animals (including horses, cows, and sheep) in the USSR had been immunised. 1% of animals developed side-effects and only 0·008%,

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0·0014%, and 0·026% of these species died, respectively. The quality of the vaccine was later improved11 and shown to be more efficient than ALV. Interestingly, killed vaccines, rather than attenuated versions, of both ALV and TLV have no influence on tumour growth. This means that the toxins of microbes and spores play an important part in the antitumour effect—as shown by the recent American report.1 In the current climate, and based on the growing evidence, the effect of dangerous infections in carcinogenesis is an area in need of further investigation. Armen K Nersesyan Laboratory of Carcinogenesis, Cancer Research Centre, Yerevan State University, 1 Alex Manoukian Street, Yerevan 25, Armenia. 1 Dunn FB. Anthrax is a cancer drug? J Natl Cancer Inst 2001; 93: 1680–83. 2 Nikolayvski GP, Frolov VI, Morozov VI. Current prophylaxis of tularemia in the USSR and further tasks. J Microbiol Epidem Immunol 1978; 10: 104–9 (in Russian). 3 Nersesyan AK, Zilfian VN, Koumkoumadjian VA. Inhibitory effect of rat immunization with tularemia vaccine on the in vivo clastogenicity of 4 anthracycline antibiotics. Mutat Res 1991: 360: 215–18. 4 Nersesyan AK, Muradyan RE. The influence of immunization with tularemia vaccine on the clastogenic action of cyclophosphamide in mice. Mutat Res 1996; 274: 311–14. 5 Nersesyan AK. DNA and chromosomal damage induced by X-rays and 131I in cells of rats immunized with tularemia vaccine. In: Disdaroglu M, Karakaya AE, (Eds.) Advances in DNA damage and repair. NATO: ASI Series—Series A: Life Sciences, 1999; 302: 475–76. 6 Nersesyan AK, Zilfian VN. The effect of tularemia live vaccine on DMBA-induced rat tumors. Anticancer Res 1990; 10: 1454. 7 Nersesyan AK, Muradyan RE. Inhibition of carcinogenic and clastogenic effects of NNDMA in rats immunized with tularemia vaccine. In: Rao RS (Ed.), Proceedings of XVI International Cancer Congress. Bologna: Monduzzi Editore, 1994: 99–102. 8 Adamyan RT. Means for use in complex treatment of patients with lung and corpus uteri cancer. Patent of Russian Federation No 2092186, 1997. 9 Nersesyan AK, Mkrtchian LN. The influence of anthrax vaccine on mutagenesis. Mutat Res 1997; 379: S117. 10 Nersesyan AK, Koumkoumadjian VA, Muradyan RE. The influence of anthrax vaccine on carcinogenesis and tumor growth. Proceedings of the First Congress of Oncologists of Georgia and Armenia, Tbilisi, Georgia, 1998: 190 (in Russian). 11 Maltsev VN, Smirnova OV, Strelnikov VA, Muravyeva LI. Radiation and vaccination. Moscow: Meditsina, 1976 (in Russian).

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