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We have previously shown that antibody dependent cellular cytotoxicity (ADCC) contributes significantly toward the therapeutic activity of an anti-CD7 antibody (HB2) and immunotoxin (HB2-Saporin) directed against disseminated human CD7+ T-cell leukaemia xenografts in SCID mice (SCID-HSB-2 mice) (Flavell et al., Cancer Res, 58, 5787 1998; Flavell et al., Br J Cancer, 83, 1755 2000). We therefore reasoned that stimulating SCID mouse ADCC should further improve the therapeutic effectiveness of both antibody and immunotoxin treatment in this in vivo model of human leukaemia. Poly inosinic:cytidylic acid (poly IC) is dsRNA that binds to TLR3 on dendritic cells resulting in enhanced ADCC. Injection of SCID mice with 100 μg Poly IC iv resulted in raised IL12 and INFγ levels at 6 hours followed by 24-48h to a modest increase in the number of splenocytes expressing the NK cell marker NK1.1 and FcγRII/III. Maximal stimulation of measurable ADCC by Poly IC in SCID mice occurred 24h after injection. Poly IC significantly improved the therapeutic performance of HB2 antibody and HB2-Saporin in SCID-HSB-2 mice when compared to identically treated animals that did not receive Poly IC. Poly IC did not improve the therapeutic effectiveness of a F(ab)2 derivative of HB2 antibody or an immunotoxin constructed with this derivative demonstrating the absolute requirement of the Fc antibody domain. We conclude from this that it is stimulation of ADCC by Poly IC that results in the significant improvement to in vivo immunotoxin activity through the combined effects of selective toxin delivery and a simultaneous augmented NK-cell-mediated attack on the same cell CD7+ target leukaemia cell.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]