Oncogene-linked in situ immunotherapy of pre-B lymphoma arising in Eμ/ret transgenic mice

We attempted to induce anti-tumour immunity for rejecting pre-B lymphoma derived from Eu/ret transgenic mice (TGM). We established pre-B-lymphoma cell lines of C57BL/6 x Balb/c background (H-2^b/d) into which H-2^k alloantigen and C3H background were introduced (retLl-6 and retL6-6), and we inoculated BCF₁, mice with these immunising tumour cells. After these tumours were rejected by alloantigen (H-^k/C3H background)-specific effector cells, the mice were challenged with the pre-B-lymphoma cell line derived from the original Eμ/ret TGM (retO-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 Eμ/ret TGM and the ret-driven melanoma cell line (MEL-ret), but not against the pre-B-lymphoma cell line from Eμ/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 Eμ/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.