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Improvement by affinity chromatography on antiidiotypic monoclonal antibodies (MAbs) of immunoreactivity and in vivo targeting of radiolabelled anti‐HMW‐MAA MAb TP61.5 in nude mice bearing human melanoma lesions
Author(s) -
Temponi Massimo,
Fawwaz Rashid A.,
Kekish Ulana,
Wang Theodore S. T.,
Ferrone Soldano
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910490426
Subject(s) - immunoscintigraphy , monoclonal antibody , in vivo , melanoma , antigen , epitope , antibody , microbiology and biotechnology , monoclonal , affinity chromatography , hybridoma technology , chemistry , biology , cancer research , immunology , biochemistry , radioimmunotherapy , enzyme
Abstract The human high‐molecular‐weight melanoma‐associated antigen (HMW‐MAA) represents a useful marker for immunoscin‐ tigraphy in patients with melanoma. Since injection of a radiolabelled anti‐HMW‐MAA monoclonal antibody (MAb) visualizes only about 60% of melanoma lesions, approaches are being developed to increase the sensitivity of immunoscintigraphy. One of them aims at improving the immunoreactivity of radiolabelled anti‐HMW‐MAA MAbs, since this approach may improve the targeting of radiolabelled MAbs to melanoma lesions. We have previously shown that affinity chromatography on insolubilized anti‐idiotypic MAbs is a useful method for purifying immunoreactive anti‐HMW‐MAA MAb TP61.5 from 125 I‐la‐ belled MAb preparations and that not all the anti‐idiotypic MAbs are useful for this purpose. Since the increasing number of available anti‐idiotypic MAbs is likely to facilitate the application of this procedure in many antigenic systems, we have now tested criteria to select anti‐idiotypic MAbs suitable for the purification procedure. Furthermore, we have investigated the effect of the increase in immunoreactivity of 125 I‐MAb TP6 1.5 on its in vivo targeting to human melanoma lesions transplanted into nude mice. Among the 3 anti‐idiotypic MAbs tested, the most effective in purifying immunoreactive MAb TP6 1.5 mole cules following radiolabelling is MAb TK7‐110, with which 125 I‐MAb TP61.5 displays an immunoreactivity similar to that displayed with melanoma cells. This parameter may represent a useful criterion to identify anti‐idiotypic MAbs suitable for the purification procedure, if the present results are confirmed with a large number of anti‐idiotypic MAbs in different antigenic systems. We have also shown that an incubation time for up to 4 hr of 125 I‐MAb TP61.5 with insolubilized MAb TK7‐110 is the most effective in increasing immunoreactivity and in recovering immunoreactive MAb applied to the affinity matrix. The increase in the immunoreactive fraction of 125 I‐MAb TP61.5 significantly increases its specific localization in human melanoma lesions transplanted into nude mice. These results suggest that purification of radiolabelled immunoreactive anti‐HMW‐ MAA MAb TP61.5 by affinity chromatography using antiidiotypic MAb TK7‐110 represents a useful approach to increasing the sensitivity of immunoscintigraphy in patients with melanoma.