How to find the core components of Mirvetuximab soravtansine?

Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) developed by ImmunoGen, Inc., targeting folate receptor alpha (FRα), which is overexpressed in several types of cancer, particularly ovarian cancer. As a novel therapeutic agent, Mirvetuximab soravtansine is designed to deliver a potent cytotoxic payload specifically to tumor cells expressing FRα, thereby minimizing toxicity to healthy tissues.

Summary of Research Progress of Mirvetuximab soravtansine

The research progress of Mirvetuximab soravtansine has been significant. The drug works by binding to FRα on the surface of cancer cells, internalizing the ADC, and releasing the cytotoxic payload within the cell. This mechanism allows for targeted delivery of the drug, enhancing its efficacy while reducing systemic side effects. Currently, Mirvetuximab soravtansine has not yet received global approval but is in advanced stages of clinical development. The drug has shown promising results in Phase III trials, particularly in patients with platinum-resistant ovarian cancer who have high levels of FRα expression. Globally, the competition in the ADC market is intense, with several other ADCs targeting various cancers at different stages of development. Key competitors include Roche's Kadcyla (T-DM1) for HER2-positive breast cancer and Seattle Genetics' Adcetris (Brentuximab vedotin) for Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Despite this competition, Mirvetuximab soravtansine stands out due to its specific targeting of FRα and its potential in treating ovarian cancer, a disease area with limited treatment options.

The overall structural characteristics of Mirvetuximab soravtansine are designed to optimize its therapeutic potential. The ADC consists of three main components: the antibody, the linker, and the cytotoxic payload. The antibody is a humanized monoclonal antibody that binds to FRα with high affinity and specificity. The linker is a cleavable linker that ensures the payload remains attached to the antibody during circulation and is released only upon internalization into the target cell. The cytotoxic payload is a maytansinoid derivative, DM4, which is highly potent against rapidly dividing cancer cells.

Structural Characteristics of Mirvetuximab soravtansine

The selection and advantages of the antibody in Mirvetuximab soravtansine are crucial for its effectiveness. The antibody used, known as IMGN853, is a humanized monoclonal antibody that binds to FRα with high affinity and specificity. FRα is a glycosylphosphatidylinositol (GPI)-anchored protein that is overexpressed in many ovarian cancers. The high affinity and specificity of IMGN853 ensure that the ADC can effectively target and bind to FRα-expressing cancer cells, thereby maximizing the delivery of the cytotoxic payload. Additionally, the antibody has been engineered to enhance its stability and reduce immunogenicity, making it suitable for repeated dosing. This engineering includes modifications to the Fc region to minimize interactions with Fc receptors, which can lead to immune-mediated side effects. The high binding affinity and low immunogenicity of the antibody contribute to the overall safety and efficacy of Mirvetuximab soravtansine.

The linker in Mirvetuximab soravtansine is a key component that ensures the stability of the ADC in circulation and the controlled release of the payload inside the target cell. The linker used is a cleavable maleimide-based linker that is stable in the bloodstream but can be cleaved by lysosomal enzymes once the ADC is internalized into the cell. This design minimizes the risk of premature release of the cytotoxic payload, which could cause off-target toxicity. The cleavable nature of the linker also allows for the efficient release of the payload within the tumor cell, ensuring maximum therapeutic effect. The linker is designed to maintain the integrity of the ADC during systemic circulation, preventing the payload from being released before reaching the target cells. This stability is crucial for minimizing systemic toxicity and ensuring that the drug reaches its intended target.

The cytotoxic drug payload in Mirvetuximab soravtansine is a maytansinoid derivative called DM4. Maytansinoids are highly potent microtubule inhibitors that disrupt the mitotic spindle formation, leading to cell cycle arrest and apoptosis in rapidly dividing cancer cells. DM4 is chosen for its high potency and ability to induce cell death at low concentrations. The payload is linked to the antibody through the cleavable linker, ensuring that it remains inactive during circulation and is only activated once inside the target cell. This design enhances the safety and efficacy of the ADC by minimizing systemic toxicity. DM4 is particularly effective against cancer cells because it targets the microtubules, which are essential for cell division. By disrupting the formation of the mitotic spindle, DM4 prevents cancer cells from completing the cell cycle, leading to cell death. The high potency of DM4 allows for the use of lower doses of the ADC, further reducing the risk of side effects.

Summary and Prospect

In summary, Mirvetuximab soravtansine represents a significant advancement in the treatment of ovarian cancer, particularly for patients with platinum-resistant disease and high FRα expression. The drug's unique mechanism of action, combined with its optimized antibody, linker, and cytotoxic payload, positions it as a promising therapeutic option. Ongoing clinical trials continue to evaluate its safety and efficacy, and if successful, Mirvetuximab soravtansine has the potential to become a standard treatment for ovarian cancer, addressing a critical unmet medical need. Future research will focus on expanding its use to other FRα-expressing cancers and exploring combination therapies to further enhance its therapeutic benefits. The detailed selection and engineering of the antibody, the stability and cleavability of the linker, and the high potency of the cytotoxic payload all contribute to the overall effectiveness and safety of Mirvetuximab soravtansine, making it a promising candidate in the field of targeted cancer therapy.

How to find the the core components of an ADC drug? 

In Patsnap Synapse and Patsnap Bio, you can find the sequence and latest research and development advances of all ADC drugs.

Taking Mirvetuximab soravtansine as an example, First, you can log in to Patsnap Synapse, enter ' Mirvetuximab soravtansine ' in the search box and click to view the details. On the details page, you can find the basic information and research progress of Mirvetuximab soravtansine.

After entering the details page, drop down to find the core Structure information of ADC drug and click view Structure in the Linker section to find the structure and type of ADC drug Linker.

The details page also lists the complete sequence information of the antibody part. By clicking on "Find Similar Sequence", you can be redirected to Patsnap Bio to search for similar sequences of the antibody.

Clicking on the sequence name will provide you with all the basic information of that sequence.

Patsnap Bio helps you turn weeks into minutes with cutting-edge AI-enabled tools built to master the complexities of sequence retrieval and automate IP analysis with precision and ease.