Replies to post #13033 on GTC Biotherapeutics (fka GTCB)

[vinmantoo]

Lew,

If the CHO cells are modifed to alter the glycosylation pattern, then that puts MAb production in the modified CHO system on a par with GTCB. MAbs produced in modified CHO cells and goats will now both be different than the orginally approved MAbs. Let's see how big pharma tries to spin it. How about "Even though the MAbs being produced in modifed CHO cells are now different from the orginal, they are different kind of difference than the goat derived MAbs so shouldn't need a different regulatory pathway for approval.

In any event, the goats will still have a major cost advantage.

Vinny

[pharm]

You forgot fructose and lactose and a lot more.

[jessellivermore]

The main difference between CHO-and mammary-derived MAbs relevant to enhanced ADCC is fucosylation.

Yes certainly..... The question is since these are two different ways of changing the "sugar end" of the MAb, how do they work and what is the signifance of each. Permit me a little speculation. In ADCC there are two actions; first there is the attachment of the MAb to the surface of the target cell at the non glycolised end, second is the binding of the NK cell to the glycolised end of the MAb. The NK cell then destroys the target cell. What I have been told is the addition of Mannose at specific locations increases the binding of the MAb to the NK cells, but does not increase the affinity of the antibody for the target cells .

Is it possible altering the fucose may increase the affinity of antibody for the target cell?? We see a similar situation in AT3 (currently AT) where Heparin will increase the activity of the serine protease, but will block the binding of the molecule to HL cell surface receptors. I did get the distinct impression from Dr. M. that the binding the NK cells is the most important action.

Please feel free to make corrections.