Ben K. Seon's letter1 focuses on the possible applications of anti-endoglin monoclonal antibodies (MAbs) in anti-angiogenic therapy, which we consider an important issue worthy of analysis and discussion. As for the comments on our article,2 we have the following responses.
First, in our immunohistochemical analyses of the different tissue samples, we performed negative controls with an isotype-matched irrelevant MAb and did not report the results. We are aware of this shortcoming and a description of the negative results obtained with this MAb could have clarified our conclusions.
Second, we reported the expression of endoglin by different cell lines as a new finding, pointing out in the Discussion that such expression is not restricted to activated endothelial cell lines but also occurs in cells of different types “at least in culture.” This point was not included in either the comparison of results obtained with A11 and other endoglin-specific antibodies or the discussion about the possible therapeutic use of these antibodies in humans.
We agree that a MAb may react differently with cultured cells than with the corresponding fresh tissue, as the results of immunohistochemical experiments do not necessarily correlate with in vivo results.
Third, in our paper we discussed the behavior of different endoglin-specific antibodies in their reactivity with normal tissue vessels and we are aware of these differences. We attributed these discrepancies to a different sensitivity in immunohistochemical procedure, different epitope exposition, different affinity of the antibodies and also differences in “normal” tissues, since these are often samples adjacent to the tumor.
Thus, even though its expression is upregulated in tumor vasculature, Dr. Seon's claim that “EDG is not a tumor-specific marker and is expressed in varying degrees in the vasculature of normal tissues” corresponds precisely to the conclusions of our article.
This lack of absolute specificity does not preclude the use of anti EDG antibodies in anti-angiogenic therapy but suggests the need for even more caution than that required when using strictly tumor specific antibodies. Thus, in our opinion, carefully planned and conducted biodistribution experiments, as well as preclinical therapeutic experiments in syngeneic experimental models are needed.