AntiGenX is a new pharmaceutical company working on developing therapeutic antib

Question

AntiGenX is a new pharmaceutical company working on developing therapeutic antibodies. However, their products so far have had varying success. Listed below are the first five drugs AntiGenX has been working on creating. Answer the questions about the results obtained with each drug.

Mutelizide (“Mute”) is a 420kDa neuroactive protein isolated from pigs that reduces the neurological effects of alcohol and is being abused by many people to be able to drink for longer periods. Researchers hope to use anti-Mute antibodies to counteract Mute and remove it from the body. After finding an anti-Mute antibody, researchers find that there are several repeating epitopes on Mute. They then measure the strength of the interaction between the anti-Mute antibody and a Mute fragment containing only one epitope. The dissociation constant (KD) turns out to be 30mM (relatively weak).

What is the term describing the strength of the interaction between the Mute fragment and the anti-Mute antibody? (1 point)

Would the binding strength of intact antibody to the intact Mute protein be higher, lower, or unchanged from 30mM? Explain your answer. (1 point)

When you make humanized antibody to Mute for therapeutic use, what isotype (class) would optimize the strength of its binding? Why? (1 point)

Although binding strength does contribute to the effectiveness of an antibody, it is not the only factor. Use the included tables (on next page) to consider other important biological activities that could contribute to anti-Mute’s level of protective activities in vivo then explain if you feel that the isotype you listed for iii is the best choice. If not, explain why. Also explain which isotype would you pick and why? (2 points)

Functional activity Neutralization Opsonization Sensitization for killing by NK cells Sensitization of mast cells Activates complement system Distribution IgM IgD IgG1 IgG2 IgG3IgG4 IgA IgE Transport across epithelium Transport across placenta Diffusion into (dimer) extravascular sites monomer) Mean serum level (mgom) 1.5 0.049 0.5 2.1 3x10-5 Figure 10.27 Janeway's Immunobiology, 9th ed. (© Garland Science 2017)

Explanation / Answer

1. ANTIGEN-ANTIBODY INTERACTION is the term describing the strength of the interaction between the Mute fragment and the anti-Mute antibody.

2. The binding strength intact antibody to the intact Mute protein be higher from 30mM, because the intact Mute protein contains more epitopes.

3. While making humanized antibody to Mute for therapeutic use, IgG isotype would optimize the strength of its binding, because it has high serum concentration and serum half-life.

4. Immunoglobulin G3 is the best choice, as it has high functional activities and with maximum distribution than other subtypes.

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