TARGETING BCL1 LYMPHOMA WITH ANTIIDIOTYPE ANTIBODIES - BIODISTRIBUTION KINETICS OF DIRECTLY LABELED ANTIBODIES AND BISPECIFIC ANTIBODY-TARGETED BIVALENT HAPTENS

The mouse BCL1 lymphoma model has been used for evaluating immunothera py with anti-idiotype (anti-1d) antibodies, including 1d immunisation, IgG therapy and bispecific (Bs) antibody-targeted cytotoxicity. Here, we provide quantitative data on the targeting of small (25 +/- 12 mg) intrasplenic BCL1 tumours, using anti-1d IgG, F(ab')(2) and anti-1d x antihapten BsF(ab')(2) covalently labelled with (125)iodine, as well as noncovalent complexes of BsF(ab')(2) and I-125-labelled bivalent ha pten. The results are the following: 1) up to 115% of the injected dos e per gram (% ID/g) of spleen can be localised in the first hour, corr esponding to approximately 600% ID/g of tumour; 2) localisation is spe cific for cell-surface 1d; 3) optimal doses can overcome circulating 1 d; 4) circulating 1d markedly increases the catabolism of IgG, thus im pairing tumour localisation; 5) bivalent reagents ave internalised by the target cells; 6) iodine covalently bound to bivalent antibodies [I gG, F(ab')(2)] is rapidly (T-1/2: 6-9 hr) released from the tumour; in contrast, the bivalent hapten is retained for a longer time (T-1/2: 2 5 hr); and 7) in the absence of bivalent hapten, the monovalent BsF(ab ')(2) is not rapidly internalised and dissociates from tumour cell-sur face 1d. Our results suggest that monovalent anti-1d, lacking Fc, can efficiently be targeted to the BCL1 tumour surface. For radioimmunothe rapy, the intracellular targeting of catabolism-resistant I-125-labell ed bivalent hapten provides optimal tissue selectivity.