ZMAB – Human IgG4 with aglyco-Fc
A CDR-silenced human IgG4 antibody with an aglycosylated Fc domain (A297), PZHU004 exhibits attenuated bindings to human Fcγ receptors, but its binding to human FcRn is not affected.
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What is a Z-MAB?
Z-MAB – A next generation control antibody reagent, Z-MAB stands for Zero-binding monoclonal Antibody.
Z-MAB is a genetically engineered antibody variant whose antigen-binding capacity has been eliminated. Z-MAB is suitable to be used as an unbiased control agent for testing specific activities of an antibody of interest.
How are Z-MABs created?
Starting with an antibody from a well established antibody drug, we identified the critical amino acid residues in all 6 complementary determining regions (CDRs), engineered selected combinatorial variants and tested for the reduction/loss of their antigen-binding activities. Final candidate Z-MABs exhibit excellent CMC and pharmacokinetic properties.
What unmet needs are Z-MABs meant to serve?
Choosing a control antibody is probably the most unscientific component for testing the specific activity of an antibody of interest. Control antibodies commercially available thus far include antibodies with no known antigens, e.g. MOPC21; antibodies raised against antigens of evolutionarily distant species, e.g. anti-KLH; antibodies reactive with a known antigen that is distinct from the antigen of interest. If cross-reactivity or high background is observed, most researchers simply move to the next control antibody available until an “ideal” control antibody is found, that is, until the expected result is observed. Z-MAB has no active antigen-binding activity, and yet retains the overall antibody structure and conformation. It is therefore a bona fide control agent for testing antibodies.
How can Z-MABs help antibody-based research and drug development?
Since all isotype Z-MABs of the same species (mouse or human) share the same Ig variable regions, one simply selects an isotype-matched Z-MAB and uses it as a control with peace of mind, no longer blindly sifting through a collection of alleged “control” antibodies to hopefully land with the expected result(s). In addition, Z-MABs are particularly useful in animal disease models for antibody drug development where the conventional control antibodies frequently lead to unexpected efficacies.
What Z-MABs are available?
Currently, both mouse and human IgG Z-MABs are available. In addition to the isotype matched Z-MABs, Z-MABs with an aglycoyslated Fc domain are available for investigating antibody activities that involve binding to Fc receptor.