Oncogene-linked in situ immunotherapy of pre-B lymphoma arising in E mu/ret transgenic mice.
We attempted to induce anti-tumour immunity for rejecting pre-B lymphoma derived from E mu/ret transgenic mice (TGM). We established pre-B-lymphoma cell lines of C57BL/6 x Balb/c background (H-2b/d) into which H-2k alloantigen and C3H background were introduced (retL1-6 and retL6-6), and we inoculated BCF1 mice with these immunising tumour cells. After these tumours were rejected by alloantigen (H-2k/C3H background)-specific effector cells, the mice were challenged with the pre-B-lymphoma cell line derived from the original E mu/ret TGM (ret0-2). All non-immunised control mice died within 80 days, whereas half the immunised mice survived for over 300 days. The immunity was also effective against primary pre-B-lymphoma cells from E mu/ret TGM and the ret-driven melanoma cell line (MEL-ret), but not against the pre-B-lymphoma cell line from E mu/myc TGM. This immunity was at least in part mediated by cell-mediated cytotoxicity that was specific to the ret oncogene product or ret-regulated antigen. Next we immunised E mu/ret TGM by inoculating them with retL6-6 cells once every 2 weeks beginning at the age of 1 month. Interestingly, this immunisation enabled the TGM to survive longer than the non-immunised control group (P < 0.05). Moreover, 2 of 11 transgenic mice receiving such immunisation were free from both macroscopic and microscopic tumours at the time when all of the 12 non-immunised control TGM had died from their tumour. This provides a new model for oncogene-linked immunotherapy research.
Ichihara
M
M
Department of Immunology, Nagoya University School of Medicine, Japan.
Iwamoto
T
T
Isobe
K
K
Takahashi
M
M
Nakayama
A
A
Pu
M
M
Dai
Y
Y
Parashar
A
A
Ohkus
K
K
Kato
M
M
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D007167:Immunotherapy; D008214:Lymphocytes / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009857:Oncogenes; D011230:Precancerous Conditions / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013154:Spleen / Q000276:immunology