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Inhibition of Friend Leukemia Cell Visceral Metastases by a New Monoclonal Antibody and Role of the Immune System of the Host in Its Action¹

Departments of Virology [A. S., L. S., F. B.], and Immunology [S. B., M. C.], Instituto Superiore di Sanità, 00161 Rome, Italy, and Laboratory of Viral Oncology, Institut de Recherches Scientifiques sur le Cancer, 94801 Villejuif, France [I. G., D. C., C. M., P. E., M-T. M.]

We developed a syngeneic mouse IgG2a monoclonal antibody (MAb) A9D41 directed against the Friend leukemia virus envelope gp70 antigen present on the cell surface membranes of virus producer 3Cl8 Friend leukemia cells (FLC). A9D41 showed a marked antitumor activity in DBA/2 mice given injections of gp70 positive 3Cl8 FLC, but it was ineffective in mice given injections of gp70 negative 745 FLC or unrelated tumor cells. A9D41 was particularly effective in inhibiting the development of 3Cl8 FLC liver and spleen metastases. MAb was also effective as adjuvant therapy in inhibiting visceral metastases after excision of an established s.c. FLC tumor, and combined therapy of A9D41 with mouse interferon /ß was more effective than MAb or interferon /ß alone. The immune system of the host played a decisive role in the antimetastatic action of A9D41. Thus, although MAb was cytotoxic for 3Cl8 FLC in vitro in the presence of rabbit complement, the F(ab')₂ fragment was ineffective in vivo, and the antitumor effect of MAb was abolished in mice treated with an antibody to CD4 and diminished in natural killer cell-deficient beige and athymic nude mice. MAb-treated mice surviving injection of FLC developed an immune response to 3Cl8 FLC.

¹ This work was supported by grants from the Commission des Communautés Européennes (Contract SCI-0234), Association pour la Recherche sur le Cancer, the Fondation pour la Recherche Médicale, the Associazione Italiana Ricerca sul Cancro, and the Programma Italia, VSA Sulla Terapie dei Tumori (1990).

² To whom requests for reprints should be addressed, at Laboratory of Viral Oncology, Institut de Recherches Scientifiques sur le Cancer, BP 8, 94801 Villejuif Cedex, France.

Received 12/19/91. Accepted 2/11/92.