Figure 1. Drug-induced xenogenization (DIX).

Figure 1A. Typical DIX pattern indicating the kinetics of the appearance of leukemia cell immunogenicity in CD2F1 mice exposed to DTIC (50 mg/Kg/day ip, from day 1 through day 10) after ip challenge with 10⁵ L5178Y leukemia cells of DBA/2 origin. At transplant generation 4, 2 out of 6 control mice not subjected to DTIC treatment, survived longer than the 60 days of observation period. At transplant generation 5, all untreated mice survived beyond the 60 day-observation period. On the other hand, all CD2F1 recipients treated with DTIC or immunodepressed by pre-treatment with cyclophosphamide (Cy, 180 mg/Kg, 6 h before tumor challenge) died with evidence of generalized leukemia at the autopsy. Figure 1B. Extent of immunogenicity levels of xenogenized leukemia cells (L1210/DTIC x 5, i.e. L1210 leukemia of DBA/2 origin, treated with DTIC 100 mg/Kg/day for 10 days, for 5 transplant generations). The number of dead mice over the total injected are indicated on the top of each column. Two types of recipient mice were used, i.e. the H-2b homozygous C57BL/10.129(5M) mice syngeneic with L5MF-22 leukemia, and the CD2F1 hosts (H-2d/H-2d), fully histocompatible with L1210 leukemia. The degree of full compatibility between host and tumor is indicated by the observation that almost all CD2F1 mice died for leukemia even after challenge with as low as 1 L1210 cell ip. In addition all C57BL/10.129(5M) mice died with generalized leukemia after injection of 10⁷ cells of the syngeneic L5MF-22 leukemia. The degree of immunogenicity of L1210/DTIC x 5 cells for the H-2-compatible CD2F1 hosts appears to be comparable to that of the H-2-incompatible L5MF-22 for the same CD2F1 recipients. In fact, up to 10⁷ cells of both leukemias were completely rejected by CD2F1 mice that survived beyond the 60 day observation period. On the other hand, all immunodepressed recipients, either irradiated (Irr, 4 Gy delivered on day -1 before challenge), pretreated with cyclophosphamide (Cy, 180 mg/Kg administered 6 h before tumor transplantation) or treated with DTIC (DTIC 100 mg/Kg/day for 10 days) died after challenge with the same number of xenogenized L1210 leukemia cells.