We have investigated the efficacy of a F(ab'gamma)2 bispecific antibody (BsAb) with dual specificity for the CD7 molecule in one Fab arm and for the
ribosome inactivating protein (rip)
saporin in the other arm, for delivering
saporin to the acute T-cell leukaemia cell line HSB-2.
Saporin titration experiments revealed that BsAb increased the toxicity of
saporin 435-fold for HSB-2 cells, reducing the IC50 for
saporin alone from 0.1 mumol to 0.23 nmol when BsAb was included. The rate of
protein synthesis inactivation brought about by BsAb-mediated toxin delivery to HSB-2 cells was very similar to that described for conventional
immunotoxins (IT's) with a t10 (time taken for a one log inhibition of
protein synthesis compared with controls) of 46 h obtained at a
saporin concentration of 1 nmol and 226 h at 0.1 nmol. BsAb titration studies demonstrated a clear dose response effect of BsAb concentration on target cell
protein synthesis inhibition and cell proliferation. The absolute specificity of toxin delivery was unequivocally demonstrated by a failure of BsAb to deliver an effective dose of
saporin to the CD7- cell line HL60 and by the blocking of BsAb-mediated delivery of
saporin to HSB-2 cells with an excess of F(ab)2 fragments of the anti-CD7 antibody, HB2. These studies have clearly demonstrated the effectiveness of this BsAb for delivering
saporin to a
T-ALL cell line utilising CD7 as the target molecule on the cell surface. BsAb's would therefore appear to offer a realistic alternative to IT's for toxin delivery to tumour cells and may even offer certain advantages over conventional IT's for clinical use.