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Xenogenization of a Mouse Lung Carcinoma (3LL) by Transfection with an Allogeneic Class I Major Histocompatibility Complex Gene (H-2L^d)¹

Laboratory of Pathology [T. I., F. O., N. T., M. H., H. K.] and Laboratory of Molecular Genetics [S. Y., T. O., N. K.], Cancer Institute, Hokkaido University School of Medicine, Sapporo 060, Japan.

We investigated the tumorigenicity and immunogenicity of tumor cells transfected with an allogeneic class I major histocompatibility complex gene. A single clone (3LL/3) from a Lewis lung carcinoma in the C57BL/6 strain (H-2^b) was cotransfected with a BALB/c genomic clone containing an H-2L^d gene and a bacterial neo gene conferring resistance to G418. Three L^d-positive, three L^d-negative, and two Neo^r clones were selected by means of a ¹²⁵I-protein A binding assay using an anti-H-2L^d monoclonal antibody. The antigenic expression of the H-2L^d gene products was only 20–40% on the L^d-positive clones compared with Meth-A tumor cells of BALB/c mice. The 50% lethal tumor dose of these clones in C57BL/6 mice was 5.6 x 10⁶ in the L^d-positive clones, but only 1.3 x 10⁵ in the 3LL/3 parent clone, 1.2 x 10⁵ in the Neo^r clones, and 2.2 x 10⁵ in the L^d-negative clones. The tumorigenicity of the L^d-positive clones was, therefore, reduced to less than 1/40 of that of the parent tumor cells. The decreased tumorigenicity of the L^d-positive clones was abrogated in mice irradiated with 600 rads. After inoculation and spontaneous regression of the viable L^d-positive clone cells, the mice acquired transplantation resistance against the challenge of a parental 3LL/3 tumor. However, the immunogenicity variation between L^d-positive, L^d-negative, Neo^r, and 3LL/3 parent clones showed no statistical difference. These results indicate that tumor cells transfected with an allogeneic class I H-2 gene can express an H-2 foreign antigen, can regress in syngeneic hosts, and can induce antitumor transplantation resistance against the original tumors, although they are not able to enhance their immunogenicity.

¹ Supported in part by a Grant-in-Aid for Cancer Research from the Japanese Ministry of Education.

² To whom requests for reprints should be addressed, at Hokkaido University, Pathology Cancer Institute, Kita-15, Nishi-7, Sapporo 060, Japan.

Received 6/ 5/86. Revised 11/ 3/86. Revised 3/ 6/87. Accepted 3/17/87.

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