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Anti-MMAE (Monomethyl auristatin E) Antibodies and MMAE Conjugates: For PK/PD Studies on MMAE-ADC

Antibody-drug conjugates (ADCs) are regarded as a novel class of powerful therapeutic agents for cancer therapy, which consist of a monoclonal antibody (mAb) covalently bound with a cytotoxic drug through a chemical linker. mAb recognize antigens overexpressed on the surface of tumor cells, and cytotoxic payload is responsible for the execution of tumor cell killing. Monomethyl auristatin E (MMAE) is the most widely used payload in ADC design. MMAE is a potent antimitotic drug that exerts its action by blocking the tubulin polymerization process resulting in cell cycle arrest and apoptosis. It has shown potent activity in pre-clinical studies, both in vitro and in vivo, against a range of lymphomas, leukemia and solid tumors. In International Nonproprietary Names for mAb-MMAE-conjugates, the name vedotin refers to MMAE plus its linking structure to the antibody. As of 2021, three MMAE-based ADCs have been licensed by the U.S. Food and Drug Administration (FDA).

Structure of Polatuzumab vedotin Fig. 1 Structure of Polatuzumab vedotin
(Dean AQ, et al. 2021)

Table 1 Three FDA Approved MMAE-based ADCs

ADC Trade Name Approval Year Target Antibody Linker
Brentuximab vedotin Adcetris® 2011 CD30 Chimeric IgG1 Valine-citrulline
Polatuzumab vedotin Polivy® 2019 CD79b Humanized IgG1 Valine-citrulline
Enfortumab vedotin Padcev® 2019 Nectin-4 Human IgG1 Valine-citrulline

ADCs are complex molecules with unique critical quality attributes. Considering the heterogeneity and complex changes in ADC concentration and composition after ADC administration, three analytes are routinely measured in order to characterize the PK properties of an ADC: antibody-conjugated MMAE (acMMAE), total antibody, and unconjugated MMAE. Creative Diagnostics has developed anti-MMAE antibodies and paired conjugates suitable for ADC ELISA assay development. It can be used in the quantitative determination of antibody-MMAE-conjugate level in test sample for pre-clinical and clinical pharmacology study of MMAE ADC.

Product List

Cat_N Product Name
DAG-WT669 MMAE [KLH]
DAG603S MMAE [BSA]
DAG-WZ1001 MMAE [HRP]
CABT-L3100 Rabbit Anti-vc-PAB-MMAE polyclonal antibody
CABT-B8992 Anti-MMAE monoclonal antibody, clone 3F3
DEIABL312 MMAE ADC EIA Kit
DEIABL314 Intact MMAE ADC ELISA Kit

SDS-PAGE analysis of mAb Fig. 2 SDS-PAGE analysis of mAb
(#CABT-B8992)

Bioactivity & Stability

Coating MMAE [BSA] (#DAG603S), 0.5 ug/ml
Sample Anti-MMAE monoclonal antibody, clone 3F3 (#CABT-B8992), 0-250 ng/ml
Detection Rabbit anti-Mouse IgG-HRP, 1:4,000

Anti-MMAE Antibodies and Conjugates: For PK/PD Studies on MMAE-ADC

Anti-MMAE monoclonal antibody is stable at 37°C for 24 hours, equivalent to store at -80°C for 4.5 years without performance reduction. Welcome to contact us for more validation and testing data.

References:

  1. Khongorzul P, Ling CJ, Khan FU, et al. (2019). Antibody-Drug Conjugates: A Comprehensive Review. Molecular Cancer Research. 18 (1): 3–19.
  2. Dean AQ, Luo S, Twomey JD, et al. (2021). Targeting cancer with antibody-drug conjugates: Promises and challenges. mAbs. 13(1), 1951427.
  3. Akaiwa M, Dugal-Tessier J, Mendelsohn BA. (2020). Antibody-Drug Conjugate Payloads; Study of Auristatin Derivatives. Chemical and Pharmaceutical Bulletin (Tokyo). 68(3):201-211.
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