Established in 2004, Creative Biolabs, a highly specialized company in advanced antibody biochemistry and engineering, released a novel, high-quality, maytansinoid-payload for the development of antibody-drug conjugates
With years of experience and based on the company’s advanced DrugLnk synthetic chemistry platform, Creative Biolabs has created a comprehensive offering for antibody-drug conjugates (ADCs) developments.
As members of the ansamycins superfamily, maytansine and the chemical derivatives of maytansine, called maytansinoid, contains 19-member macrocyclic lactams attached to a chlorinated benzene. Originally isolated from an Ethiopian shrub Maytenus ovatus, maytansine exerts extremely high anti-mitotic potency.
Maytansinoids are microtubule-targeting agents that share same binding site with vinca and function by depolymerizing microtubules and arresting cells in the mitosis stage. The cytotoxicity of these agents is more than a 100-fold higher than vinca alkaloids, making them suitable candidates in anti-cancer therapies utilizing tissue-specific drug delivery strategies, such as antibody-drug conjugates.
Maytansinoids exert cytotoxicity against a number of tumor cell lines and inhibit tumor growth in vivo. In human clinical trials, maytansine have showed a small therapeutic window due to its neurotoxicity and harmful effects on the gastrointestinal tract.
However, antibody-drug conjugate or ADC significantly increase the therapeutic window of maytansinoids comparing to the free drugs, enabling the usage of an otherwise highly toxic drug in cancer treatments.
Linkers accommodate different conjugation chemistries on both antibodies and payload drugs. They are an important portion in an ADC because they not only contribute to the stability of the complex in systematic circulation but also dictate the payload release mechanisms once internalized and trafficked into designated cellular locations. We commonly categorize linkers based on their release mechanisms into cleavable linkers (peptide linkers, β-glucuronide linkers, pH-sensitive linkers, and Glutathione-sensitivity linkers) and non-cleavable linkers.
As tubulin inhibitors, maytansinoids and its analogues inhibit the assembly of microtubules by binding to tubulin at or near the vinblastine-binding site.
Maytansinoid can decrease microtubule dynamic instability and cause mitotic arrest in cells, similar to the MOA of vinblastine. We can provide several antibody-maytansinoid conjugates as good anti-cancer candidates, such as T-DM1 (trastuzumab-MCC-DM1).
It is an ADC in which maytansinoid is conjugated to the anti-HER2 antibody trastuzumab showed superb efficacy against metastatic breast cancer. Meanwhile, lorvotuzumab mertansine (huN901-SPP-DM1), a CD-56 targeting ADC, has also revealed hopeful results in solid and liquid tumors that express CD56.
Last Editorial Review: June 24, 2018
Featured Image: Life scientists researching in laboratory. Focused female life science. Courtesy: © 2010 – 2018. © Fotolia. Used with permission. Figure 1.0: Chemical structures of maytansine and its derivatives. Both DM1 and DM4 have been used as payloads for ADC development. Courtesy: © 2010 – 2018. © Creative BioLabs . Used with permission.
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