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Z-MAB – A next generation control antibody reagent, Z-MAB stands for Zero-binding monoclonal Antibody.
What is a Z-MAB?
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?
Our Z-MAB product line includes the mostly commonly used isotypes of mouse, human and rat origins. For mouse Z-MABs, the IgG2a isotype (PZMU001) was engineered from the OKT3 (a mouse anti-human CD3 antibody) by CDR-silencing. The IgG1 isotype Z-MAB was generated by joining the variable regions of PZMU001 to the constant regions of a mouse IgG1 antibody. Additional mouse antibody isotypes were generated using the same recombinant method. Human and rat Z-MABs were similarly engineered from Avastin (a humanized anti-VEGF antibody) and 53.6.72 (a rat anti-mouse CD8-alpha antibody), respectively. As such, all isotype Z-MABs of the same species share the same CDR-silenced variable regions. With the Z-MABs control agent, one no longer has to deal with the complications associated with poorly characterized “control” antibodies. In this regard, Z-MABs are particularly useful in animal disease models for antibody drug development where the use of unqualified control antibodies frequently leads to unexpected efficacy and for FACS analysis where the background staining frequently makes proper gating a challenge.
What Z-MABs are available?
Curretnly, we offer a total of 16 Z-MABs of mouse, human and rat origin (please see the listing above). In addition to the isotype matched Z-MABs, Z-MABs carrying aglycoyslated Fc domain are available as excellent control agents for antibodies whose Fc regions are not glycosylated, enzymatically or recombinantly.