Targeting BCL1 lymphoma with anti-idiotype antibodies: biodistribution kinetics of directly labeled antibodies and bispecific antibody-targeted bivalent haptens

Int J Cancer. 1997 Jun 11;71(6):1000-9. doi: 10.1002/(sici)1097-0215(19970611)71:6<1000::aid-ijc16>3.0.co;2-h.

Abstract

The mouse BCL1 lymphoma model has been used for evaluating immunotherapy with anti-idiotype (anti-Id) antibodies, including Id 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-Id IgG, F(ab')2 and anti-Id x anti-hapten BsF(ab')2 covalently labelled with 125iodine, as well as noncovalent complexes of BsF(ab')2 and 125I-labelled bivalent hapten. The results are the following: 1) up to 115% of the injected dose per gram (% ID/g) of spleen can be localised in the first hour, corresponding to approximately 600% ID/g of tumour; 2) localisation is specific for cell-surface Id; 3) optimal doses can overcome circulating Id; 4) circulating Id markedly increases the catabolism of IgG, thus impairing tumour localisation; 5) bivalent reagents are internalised by the target cells; 6) iodine covalently bound to bivalent antibodies [IgG, 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): 25 hr); and 7) in the absence of bivalent hapten, the monovalent BsF(ab')2 is not rapidly internalised and dissociates from tumour cell-surface Id. Our results suggest that monovalent anti-Id, lacking Fc, can efficiently be targeted to the BCL1 tumour surface. For radioimmunotherapy, the intracellular targeting of catabolism-resistant 125I-labelled bivalent hapten provides optimal tissue selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / immunology*
  • Antibodies, Bispecific / immunology*
  • Cell Division / immunology
  • Haptens / immunology*
  • Iodine Radioisotopes
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / pathology
  • Mice
  • Mice, Inbred BALB C
  • Spleen / immunology

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Bispecific
  • Haptens
  • Iodine Radioisotopes