As I was preparing the attached paper, it's mentioned that CD20 receptor is expressed in both normal and lymphoid cancer cells (page # 3, highlighted), yet, they designed monoclonal antibodies that target it...
How it can differentiate if it binds to both?
You forgot to attach the paper.
But for the things you mentioned two things come to my mind as possible theories:
Those are just theories since I haven't read the paper you mentioned.
I have another question :)
they mentioned that 2 mRNA for two light chains of the monoclonal antibody are encoded while there should be one (which is the one produced by the B cell )... they say that the myloma cell produced the other light chain (while it'sfunction is only to make hybrodma immortal) ...the possible cause of that is not mentioned... can you suggest possible reason of this plz?
Thanks
I'm not very experienced in antibody production. Maybe the article bellow may help you.
http://www.ncbi.nlm.nih.gov/pubmed/6780916
http://www.bloodjournal.org/content/103/10/3869?sso-checked=true
1. I don't think that Rituximab differentiates between healthy and tumor cells expressing CD20. However, in disease CD20-expressing tumor cells are way more abundant. Thus, the positive effects outweigh the negative ones. Indications that it also targets healthy cells come from the observation that it seems to be active in other possibly antibody-mediated diseases like rheumatoid arthritis and from side effects like fatal reactivation of Hepatitis B.
2. They state in their paper that the CDR3 of both light chains are identical and underwent hypermutation. Therefore, they probably derive from antigen-specific B cells and not the myeloma cell line. I have too little expereince with hybridoma to know if this is possible, but maybe the CDR3 of the light chain recombined with other light chain sequences of the myeloma cell line. Or, although unlikely maybe their hybridoma is simply not monoclonal.
There are several GENERAL reasons that go beyond CD20.
1. The density of the target antigen might be different on the neoplastic vs normal cell,
2.if the effector mechanism for killing involves another molecule on the cell surface such as an Fc receptor, this might be different on the two types of cells.
3. One cell might be rapidlying cycling and the othe not. This can make a difference. depending upon how the antibody mediates is cytotoxic activity.
4. The location of the normal and neoplastic cell and hence access to the antibody might differ.
Expression of the target antigen ONLY does not predict the efficiency of killing a given cell.
Given those GENERAL comment ts, in many cases normal cells ARE damaged. This is certainly true of anti- CD20... BUT NORMAL B CELLS ARE REGENERATED.
I agree with Ellen. I'd like to add another point concerning B cell depletion therapies. Some chronic lymphocytic leukemias have relatively low levels of CD20 but express high levels of CD37. Thus, targeting a non-CD20 surface receptor may make sense, and not only that, the combined binding of CD20 and CD37 (which signals differently than CD20) may lead to more cell death as well as ADCC.
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