Suitable for use in ELISA. Each laboratory should determine an optimum working titer for use in its particular application. Other applications have not been tested but use in such assays should not necessarily be excluded.
Target
Alternative Names
Mertansine; Ravtansine; soravtansine; DM1; DM4
Citations
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Background
DM1 and DM4 are maytansinoid compounds that have gained significant attention in the field of targeted cancer therapy. Both DM1 and DM4 possess potent cytotoxicity, making them attractive candidates for targeted cancer therapy. DM1, also known as emtansine, is a synthetic derivative of a naturally occurring maytansinoid. It functions by binding to tubulin, a protein involved in microtubule assembly and stabilization. By binding to tubulin, DM1 disrupts the normal functioning of microtubules, leading to cell cycle arrest and ultimately inducing cell death. DM1 has shown particular efficacy against HER2-positive breast cancer and has been utilized in the development of antibody-drug conjugates (ADCs) such as T-DM1 (trastuzumab emtansine). DM4 is another synthetic derivative of a maytansinoid and shares similar mechanisms of action with DM1. DM4 has been explored for its potential in targeted cancer therapy, particularly in the development of ADCs. ADCs incorporating DM4, such as lorvotuzumab mertansine, have shown promise in the treatment of various cancers, including CD56-positive tumors.
Figure 1. Structures of maytansine, DM1 and DM4. (Source: Bouchard, H. et al., 2014)
Rabbit Anti-DM1/4 polyclonal antibody is a specific type of polyclonal antibody that is raised in rabbits against the maytansinoid compounds DM1 and DM4. In research, Rabbit Anti-DM1/4 polyclonal antibody can be used to detect and quantify DM1/4 in biological samples, such as cell lysates, tissue extracts, or biofluids. It can be employed in techniques like Western blotting, immunohistochemistry, or enzyme-linked immunosorbent assay (ELISA) to study the expression and distribution of DM1/4 in different samples.
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References
Antibody-maytansinoid conjugates: A new strategy for the treatment of cancer
Early clinical development in the field of targeted delivery of cytotoxic drugs to tumors using antibodies failed to achieve effective, well-tolerated anticancer products. In recent years, several new highly potent cell-killing agents, such as thiol derivatives of the potent antimitotic microtubule agent maytansine, developed by ImmunoGen, are being utilized to make a new generation of antibody-drug conjugates (ADCs). Several antibody-maytansinoid conjugates (AMCs) have shown encouraging efficacy in clinical trials, including trastuzumab-DM1 (T-DM1), which targets HER2+ breast cancer, SAR-3419, which targets CD19 expressed on B-cell malignancies, and IMGN-901, which targets CD56 expressed on both solid tumors (small cell lung cancer and other neuroendocrine tumor types) and hematological tumors, including multiple myeloma. Besides their demonstrated efficacy in phase I and/or phase II clinical studies, these AMCs are well tolerated, with no clinically significant myelosuppression, suggesting that AMC compounds are well suited for evaluation in combination treatment regimens. Maytansinoids are payloads for antibody-mediated delivery that are realizing the promise of ADCs for improved targeted therapy in cancer patients. Copyright ? 2010 Prous Science, S.A.U. or its licensors. All rights reserved.
Targeting HER2-Positive Breast Cancer with Trastuzumab-DM1, an Antibody–Cytotoxic Drug Conjugate
Cancer Research
Authors: Lewis Phillips G D, Li G, Dugger D L, et al.
HER2 is a validated target in breast cancer therapy. Two drugs are currently approved for HER2-positive breast cancer: trastuzumab (Herceptin), introduced in 1998, and lapatinib (Tykerb), in 2007. Despite these advances, some patients progress through therapy and succumb to their disease. A variation on antibody-targeted therapy is utilization of antibodies to deliver cytotoxic agents specifically to antigen-expressing tumors. We determined in vitro and in vivo efficacy, pharmacokinetics, and toxicity of trastuzumab-maytansinoid (microtubule-depolymerizing agents) conjugates using disulfide and thioether linkers. Antiproliferative effects of trastuzumab-maytansinoid conjugates were evaluated on cultured normal and tumor cells. In vivo activity was determined in mouse breast cancer models, and toxicity was assessed in rats as measured by body weight loss. Surprisingly, trastuzumab linked to DM1 through a nonreducible thioether linkage (SMCC), displayed superior activity compared with unconjugated trastuzumab or trastuzumab linked to other maytansinoids through disulfide linkers. Serum concentrations of trastuzumab-MCC-DM1 remained elevated compared with other conjugates, and toxicity in rats was negligible compared with free DM1 or trastuzumab linked to DM1 through a reducible linker. Potent activity was observed on all HER2-overexpressing tumor cells, whereas nontransformed cells and tumor cell lines with normal HER2 expression were unaffected. In addition, trastuzumab-DM1 was active on HER2-overexpressing, trastuzumab-refractory tumors. In summary, trastuzumab-DM1 shows greater activity compared with nonconjugated trastuzumab while maintaining selectivity for HER2-overexpressing tumor cells. Because trastuzumab linked to DM1 through a nonreducible linker offers improved efficacy and pharmacokinetics and reduced toxicity over the reducible disulfide linkers evaluated, trastuzumab-MCC-DM1 was selected for clinical development.
COA
Publication 
Figure 1. Structures of maytansine, DM1 and DM4.
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