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Re: jbog post# 1957

Tuesday, 10/03/2006 4:10:22 PM

Tuesday, October 03, 2006 4:10:22 PM

Post# of 4764
Re: jbog <For all practical purposes no. Panitumumab exhibits a much higher affinity than Erby, in other words it attacts the tumor egfr more efficiently. >

Just a quick comment. There is not necessarily a direct correlation with EGFR affinity and the ability of an AB to penetrate/attack tumors.

A 2003 JBC paper (Vol. 278, No.44, 43496-43507) from Imclone may be relevant to this discussion on AB affinity. In the discussion section, the authors address antibody affinities as it relates to therapeutic efficacy (based on the work of other laboratories). The key points are outlined below:

-- The affinity of a MAB needs to be 10^-8 M or greater
-- Some investigators presume that higher affinity is better
-- Do affinity increases beyond 10^-9 M enhance efficacy? Limited data on this question. However, there is one study (Adams et. al.) which looked at ErbB-2 ABs with increasing affinities. ABs with affinities (10^-8 M--10^-9 M) penetrated the tumor more efficiently than antibodies with higher affinities (10^-10 M). The higher affinity antibodies were more likely to be trapped around the perivascular tumor cells.
--My read?there may be a point of diminishing returns in which increasing antibody affinity results in diminishing therapeutic efficacy.

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