Biointron 2024 Lunch & Learn: “Accelerating Antibody Development and ADCs”

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.