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Murine Sarcoma Virus Pseudotypes Used as Immunogens against Viral and Chemical Oncogenesis¹

Sección Leucemia Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Melo 3081, 1425 Buenos Aires, Argentina

The purpose of this study was to develop an animal system of protective immunity against oncornaviruses and to test whether such immunization had an inhibitory effect upon chemical sarcomagenesis. Several murine sarcoma virus (MSV) pseudotypes were used as immunogens and tested against themselves, against other pseudotypes, against leukemogenesis by their helper viruses, and against sarcomagenesis by 3-methylcholanthrene. Five MSV pseudotypes were obtained by rescuing complete MSV from MSV-genome carrier, nonproducer hamster tumor cells, using five different leukemia viruses as helpers. The immunogenic properties of these pseudotypes could be specified on the basis of the following observations. 1) They all induced sarcomas in newborn mice and regressing sarcoma nodules in young adult mice. After regression, most mice remained free of neoplastic disease, but some developed sarcoma or leukemia relapses. 2) They had an individual host range pattern, usually determined by the helper virus, as tested by inoculation of a constant virus dose into BALB/c, C57BL/Ka, and Swiss mice. 3) They were all immunogenic, in the sense that the first virus inoculation prevented sarcoma induction by a second challenge, either viral or cellular. 4) They were cross-reactive in vivo, one pseudotype immunizing against another, in the combinations tested. 5) They were able to immunize against leukemogenesis induced by their helper viruses. This was shown by prevention of leukemic deaths by Rauscher and Friend viruses, by a slight prolongation of survival after challenge with the Precerutti-Law leukemia virus, and by inhibition of splenomegaly by Moloney leukemia virus.

In a second stage of the study, we investigated whether immunization with any of the MSV pseudotypes had an inhibitory effect upon sarcomagenesis induced by near-threshold doses of 3-methylcholanthrene. The incidence of these sarcomas was essentially the same in virus-immunized and control mice.

It was concluded that immunizing procedures able to prevent sarcomagenesis when the inducer is a virus did not have any consistent preventive effect when the inducer was a chemical.

¹ This investigation was supported by grants from Consejo Nacional de Investigaciones Cientificas y Téchnicas and from Fundación para Combatir la Leucemia.

² Member of Research Career, Consejo Nacional de Investigaciones Cientificas y Técnicas.

³ Fellow of Consejo Nacional de Investigaciones Cientificas y Technicas.

Received 1/ 6/77. Accepted 3/14/77.

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