Biointron’s Lunch & Learn with MassBio was held in Boston, MA on May 9. The session focused on the advancements in next-generation HTP antibody and antibody-drug conjugate (ADC) development in the biopharma industry and featured two key speakers: Biointron’s SVP of R&D, Dr. Lei Shi, and ImmuVia’s CSO, Dr. Victor Goldmacher. We thoroughly enjoyed hosting the event and the audience’s strong engagement!
Dr. Lei Shi: Unlocking Hidden Efficiencies: Accelerate Your Antibody Development
Our SVP of R&D welcomed the session with a presentation on accelerating antibody discovery and development with Biointron’s high-throughput platforms. Cases discussed include:
The successful production of 818 IgGs through development of a panel of positive antibodies within two weeks.
An alpaca VHH discovery case and construction of a bispecific antibody targeting a cell surface receptor expressed on T cells. VHH antibodies can be used in a range of therapeutics including bispecific, multispecific, conjugate, CAR-T, and nanoparticle drug delivery.
Our AbDrop Antibody Discovery Platform from Single B Cells based on microfluidics technology.
Dr. Victor Goldmacher: Antibodies and Antibody-Drug Conjugates: Magic Bullets for Cancer?
The CSO of ImmuVia began with a history of ADC drug development, with scientists in the 1990s using more potent effector molecules as payloads.
1. Challenges of antibody therapy:
Need for function → Arm antibody with a cytotoxic effector molecule
Stability and safety in blood → Make sure effector molecule is very potent
Long-circulation in blood → Make sure effector molecule is inactive in the blood
Lack of immunogenicity → Humanization and human antibody technology
2. Maytansinoids and auristatins as payloads
Kadcyla (T-DM1), approved in 2013, was more efficacious than trastuzumab for HER2-positive breast cancer.
It was the start of a new era in the treatment of HER2+ cancer, and the first ever ADC for a prevalent, solid tumor indication.
3. Challenges in ADC development included:
Heterogeneous expression of target antigen
Bystander cytotoxicity of linkers
4. ADCs effective in eradication of tumors with heterogeneous expression of target antigen
Elahere (mirvetuximab soravtansine) was the first ADC to target folate receptor α, approved in 2022.
It is used to treat platinum resistant ovarian cancer, as FRα is highly expressed on ovarian cancers, and has a DM4 maytansinoid payload and cleavable sulfo-SPDB linker.
5. Solutions for the next generations of ADCs or other Ab-based cytotoxic agents:
Revolutionizing delivery through designing recombinant antibodies with markedly enhanced antigen-selective delivery into lysosomes, and side effects would be minimized due to equivalent payload delivery achieved at lower dose.
Bypassing internalization and the advent of ADC-mimetics, e.g. Cancerlysins™, which are ADC-like bispecifics that bind to cancer cells and activate the apoptotic machinery.
Thank you to everyone who joined us at MassBio! We had a fantastic time connecting with you and sharing how we can help you achieve antibody development. Our expert team would be happy to answer any follow-up questions. Feel free to email us at info@biointron.com or visit our website at www.biointron.com.
The therapeutic efficacy of antibodies is closely related to their ability to recognize and bind specific epitopes on target antigens. Epitopes, or antigenic determinants, are a group of amino acids or other chemical groups that are part of a molecule to which an antibody attaches itself. Epitope characterization can help reveal the mechanism of antibody binding and apply intellectual property (patent) protection for novel antibodies, in addition to designing antibodies with high specificity and minimal cross-reactivity.
Understanding the differences between antibody specificity and selectivity is essential for designing and interpreting antibody-based assays in research for experimental accuracy and data interpretation. Antibody specificity refers to an antibody's ability to recognize and bind to a particular epitope—a unique part of an antigen that elicits an immune response.
Antibody-based assays are essential tools in biomedical research, providing the means to detect, quantify, and visualize specific proteins or antigens within complex biological samples. These assays' efficacy hinges on the antibodies' precise properties. While affinity, avidity, specificity, and selectivity are fundamental to antibody performance, the ultimate impact of these properties is heavily influenced by the experimental context in which the antibody is employed.
Biologics, particularly antibodies, have become indispensable in biomedical research and therapeutic development. Research-use-only (RUO) biologics play a pivotal role in preclinical studies, providing researchers with the necessary tools to explore antibody functions and therapeutic potential in vivo.
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