The anti-CD7 immunotoxin HB2-SAPORIN has significant therapeutic activity in the SCID-HSB-2 model of human T-ALL (Morland et al 1994 Br J Cancer 69, 279). In contrast the same immunotoxin shows virtually no therapeutic activity against the same tumour cell line in the NOD/SCID-HSB-2 model (Flavell et al 2000 Br J Cancer 83,1755). One difference between the two animal models is the presence of defective NK cells in NOD/SCID mice compared with the possession of fully functional NK cells by SCID mice. As we have previously shown that NK cell-mediated ADCC contributes significantly to HB2-SAPORIN activity in the SCID-HSB-2 model (Flavell et al 1998 Cancer Res 58, 5787) we hypothesise that it is defective NK cell function and a consequent reduction in ADCC in the SCID/NOD-HSB-2 model that explains the reduced therapeutic efficacy of immunotoxin in these animals. To test this hypothesis we adoptively transferred splenocytes from untreated or poly inosinic:cytidilic (poly I:C) treated SCID mice to NOD/SCID-HSB-2 mice prior to their treatment with immunotoxin. Adoptive transfer of un-stimulated splenocytes to NOD/SCID-HSB-2 mice did appear to improve the therapeutic performance of immunotoxin in these animals though this was not significant when compared to that observed in sham adoptively transferred animals. However, adoptive transfer of poly I:C activated splenocytes from SCID mice to NOD/SCID-HSB-2 mice did significantly improve the therapeutic performance of HB2-SAPORIN in the NOD/SCID-HSB-2 model. These preliminary data provide some further evidence for our hypothesis that it is deficient ADCC in the NOD/SCID-HSB-2 model that is responsible for reduced immunotoxin activity.

Topics:
animal model, antibodies, antibody-dependent cell cytotoxicity, immunotoxins, mice, severe combined immunodeficiency, cell-mediated cytolysis, cancer, saporins, poly i-c

Disclosures: This work was supported by the UK based children’s leukaemia research charity Leukaemia Busters (registered charity No 1010957) of which the presenting author is now the salaried Scientific Director.; This work was supported by the UK based children’s leukaemia research charity Leukaemia Busters (registered charity No 1010957) of which the presenting author is now the salaried Scientific Director.

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2006, The American Society of Hematology
2006
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