Anti-tumour cytotoxicity of poly(A)-containing messenger rna isolated from tumour-specific immunogenic RNA

C. J. Greenup, D. A. Vallera, K. J. Pennline, B. J. Kolodziej, M. C. Dodd

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The transfer of tumour-specific cytotoxicity against a murine fibrosar-coma has been demonstrated in vitro using xenogeneic RNA extracted from tumour -cell-immune animals. Poly(A)-tailed messenger RNA from immunogenic RNA was isolated by passage through an oligo(dT)-cellulose column, and evaluated to determine whether the same tumour-specific cytotoxicity could be transferred. Aliquots of normal C3H mouse lymphocytes were treated with poly(A)-containing immune RNA, whole-cell immune RNA lacking poly(A) and total cellular immune RNA. Treated cells were tested in vitro using an adaptation of the Takasugi and Klein microcytotoxicity assay. Percent cytotoxicity was calculated using cells treated with fractions of normal RNA as control. An increase in tumour cytotoxicity was found with poly(A)-containing immune RNA. The optimum dose of poly(A)-tailed immune RNA was estimated as 6·5 µg of RNA per 4 × 106 lymphocytes. Populations of lymphocytes were separated using glass and nylon wool. T- and B -enriched populations were treated with various RNA components. The adherent cell population showed no significant cytotoxicity, whilst treatment of the nonadherent population with poly(A)-tailed immune RNA produced high levels of cytotoxicity.

Original languageEnglish (US)
Pages (from-to)55-63
Number of pages9
JournalBritish Journal of Cancer
Volume38
Issue number1
DOIs
StatePublished - Jul 1978
Externally publishedYes

Bibliographical note

Funding Information:
enter the cell, attach to the ribosomes, and then begin to translate protein. This protein could change an appropriate cell- surface receptor that commits the cell to a cellular cytotoxic response. The protein could be the light chain of an antibody molecule or a regulatory protein. It is also possible that poly(A)-tailed mRNA could be a template for reverse transcriptase, in which case a DNA copy of this message would be integrated into the cell's genome. At the present time, very little is known about gene regulation in a normal cell, much less what goes on in an immune cell or in a cell given the information from an immune cell. The active fraction of IRNA responsible for transfer of tumour-specific cytotoxicity has been isolated and further character- ized. However, IRNA fractions which mediate other types of immune reactions (e.g. blocking antibody and antibody- dependent cell-mediated cytotoxicity) may be present, and further studies on this matter are in progress in this laboratory. This work was supported, in part, by grants from The National Cancer Institute, National Institutes of Health #Ca-16867, The Ohio Chapter of the American Cancer Society, and from the Graduate School of The Ohio State University, Columbus, Ohio.

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