Inhibition of Friend leukemia cell visceral metastases by a new monoclonal antibody and role of the immune system of the host in its action.
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 3C18 Friend leukemia cells (FLC). A9D41 showed a marked antitumor activity in DBA/2 mice given injections of gp70 positive 3C18 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 3C18 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 alpha/beta was more effective than MAb or interferon alpha/beta alone. The immune system of the host played a decisive role in the antimetastatic action of A9D41. Thus, although MAb was cytotoxic for 3C18 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 3C18 FLC.
Sala
A
A
Department of Virology, Istituto Superiore di Sanità, Rome, Italy.
Gresser
I
I
Chassoux
D
D
Maury
C
C
Santodonato
L
L
Eid
P
P
Maunoury
M T
MT
Barca
S
S
Cianfriglia
M
M
Belardelli
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000917:Antibody Formation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D002455:Cell Division / Q000502:physiology; D003131:Combined Modality Therapy; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005622:Friend murine leukemia virus / Q000276:immunology*; D007167:Immunotherapy; D007275:Injections, Intravenous; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009362:Neoplasm Metastasis / Q000276:immunology / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D013160:Splenic Neoplasms / Q000517:prevention & control / Q000556:secondary; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D016898:Interferon-alpha; D016899:Interferon-beta; D003165:Complement System Proteins