Biparatopic FRα-targeted Bispecific ADC Development Service

Promising targeted treatments utilizing bispecific antibody, antibody-drug conjugates (ADC) and immunotherapy strategies in oncology have reignited interest in the tumor-associated antigen folate receptor alpha (FRα). As a leader in the ADC development field, Creative Biolabs has put a lot of energy and time into bispecific ADC research. Dual targeting of a protein by biparatopic ADC can enhance toxin delivery into tumor cells. With years of experience in the field of antibody discovery and conjugation, Creative Biolabs now provides biparatopic FRα-targeted bispecific ADCs development as well as characterization services for our global clients.

Background

Introduction of FRα

FRα, also known as FOLR1 or folate binding protein (FBP), is a glycosylphosphatidylinositol (GPI)-anchored membrane protein with a high affinity for binding and coordinating transport of the active form of folate, 5-methyltetrahydrofolate (5-MTF). FRα has been reported to be overexpressed in solid tumors such as lung, ovarian, and breast carcinomas. However, the distribution of FRα in normal human tissues is restricted to low level expression in the apical surfaces of some organs such as the kidney, lung, and choroid plexus. Its overexpression in tumors and restricted distribution in normal tissues, alongside emerging insights into tumor-promoting functions and association of expression with patient prognosis, together render FRα an attractive therapeutic target.

Fig.1 A model depicting FRα-mediated internalization of folates and regulation of cancer signaling.¹

FRα-targeted Approaches

A range of FRα-targeting approaches, including small molecules, T-cell therapies, monoclonal antibodies (mAbs), and ADCs have been developed for clinical application for both imaging and therapeutic purposes. For instance, Farletuzumab (MORab003) is a fully humanized IgG1 antibody specific for FRα, exerting antitumor activity against FRα-expressing tumor cells through antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), sustained tumor cell autophagy, and inhibition of Lyn kinase substrate phosphorylation.

Fig.2 Clinical applications of FRα-targeting agents in the diagnosis and treatment of cancer.²

Mirvetuximab soravtansine (IMGN853) is an ADC consisting of a cytotoxic agent, the maytansinoid DM4, conjugated to a humanized anti-FRα monoclonal antibody via the disulfide-containing hydrophilic linker sulfo-SPDB. Preclinical studies have demonstrated in vitro and in vivo anti-tumor activity of this ADC in models of ovarian cancer and NSCLC. MORAb-202, comprising a self-emolative Val-Cit linker and a drug-to-antibody ratio (DAR) of 4, displayed optimal biophysical properties, potent cytotoxicity across several FRα-positive cell lines, and induced a robust antitumor response in mouse models of FRα-positive human cancers.

Fig.3 Structure of IMGN853 and MORAb-202.

Our Service

Biparatopic FRα-targeted Bispecific ADCs Services

The biparatopic antibody promotes receptor internalization and lysosomal degradation, it should serve as an effective vehicle to deliver toxins into the target cells in the form of ADC. At present, Creative Biolabs is capable of developing biparatopic antibodies to distinct, non-overlapping epitopes that serve as reagents for biparatopic FRα-targeted bispecific ADC development. The best biparatopic ADC construction services against the FRα are available upon request, and we will apply our first-hand expertise to your distinct project requirements. If you are interested in our services, please do not hesitate to contact us for more details.

Highlights

• Enhanced Internalization Efficiency: Biparatopic FRα-targeted bispecific ADCs facilitate improved uptake by engaging two distinct epitopes on the FRα antigen, boosting cellular intake and degradation crucial for therapeutic efficacy.
• Increased Toxin Delivery: These ADCs optimize the delivery of cytotoxic agents into FRα-expressing tumor cells by exploiting enhanced receptor internalization, leading to more effective tumor suppression.
• Optimized Therapeutic Outcomes: Creative Biolabs' biparatopic ADCs harness dual-epitope targeting to maximize the therapeutic payload delivery to FRα-positive tumors, enhancing clinical effectiveness.
• Advanced Conjugation Technology: Leveraging state-of-the-art conjugation technologies, these bispecific ADCs maintain structural integrity while delivering potent toxins to targeted cancer cells.
• Customized ADC Development: Tailored to meet diverse research and clinical needs, these biparatopic FRα-targeted bispecific ADCs represent the forefront of personalized cancer therapy.

FAQ

1. Q: What advancements does Creative Biolabs offer in biparatopic FRα-targeted bispecific ADCs?

   A: Creative Biolabs integrates advanced antibody engineering to develop biparatopic FRα-targeted bispecific ADCs, significantly enhancing drug delivery and tumor cell targeting.

2. Q: How does Creative Biolabs enhance the targeting efficiency of FRα ADCs?

   A: By developing biparatopic antibodies, Creative Biolabs enhances the targeting and internalization of FRα ADCs, leading to improved therapeutic outcomes in cancer treatment.

3. Q: What role does FRα play in the effectiveness of biparatopic bispecific ADCs?

   A: FRα's overexpression in tumors makes it a prime target for ADCs, where dual epitope targeting by biparatopic ADCs ensures more effective toxin delivery and cancer cell destruction.

4. Q: How do biparatopic FRα-targeted ADCs improve cancer treatment?

   A: These ADCs offer precise targeting and potent cytotoxic delivery, reducing off-target effects and enhancing efficacy against FRα-expressing tumors.

5. Q: Can biparatopic FRα-targeted bispecific ADCs be customized for specific research needs?

   A: Creative Biolabs provides bespoke services to develop and tailor biparatopic FRα-targeted bispecific ADCs to meet unique research and therapeutic requirements.

6. Q: Can you describe the mechanism of action for biparatopic FRα-targeted bispecific ADCs?

   A: These ADCs employ two different epitopes on FRα to enhance receptor internalization and lysosomal degradation, effectively delivering cytotoxic drugs to cancer cells.

Featured Products

Anti-FOLR1 ADC