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Bispecific ADCs Development

Bispecific antibodies (bsAbs) and antibody-drug conjugates (ADCs) have already demonstrated benefits for the treatment of cancer in various clinical studies, showing improved drug selectivity and efficacy. The selectivity, internalization, payload delivery efficiency and acquired resistance of ADC can be greatly benefited from bispecific approaches, the generation of bispecific ADCs. Based on the well-established ADC and bsAb platforms, Creative Biolabs offers customized bispecific ADCs development services to help you optimize your ADC.

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Background

The Overview of Bispecific ADCs

ADCs are designed to be stable in circulation and to release potent cytotoxic drugs intracellularly following antigen-specific binding, uptake, and degradation in tumor cells. Efficient internalization and routing to lysosomes where proteolysis can take place are therefore essential. For many cell surface proteins and carbohydrate structures on tumor cells, however, the magnitude of these processes is insufficient to allow for an effective ADC approach. This limitation can be overcome by enhancing lysosomal ADC delivery via a bispecific approach, in which one binding domain would provide tumor specificity, whereas the other binding domain would facilitate targeting to the lysosomal compartment.

Schematic diagram of bispecific antibody structure.Fig.1 Schematic bispecific ADC.

The antibody component of a bispecific ADC is responsible for high tumor specificity and needs to be effectively internalized to deliver the payload inside the cancer cell. Many efforts have been made to optimize bispecific antibody affinity, selectivity, and pharmacokinetics to improve tumor delivery. Bispecific antibodies with strong binding to a target show high accumulation in the tumor but exhibit poor tumor penetration so a careful balancing act is required to achieve optimal therapeutic efficacy. Bispecific ADCs are in development as a viable route to increase tumor selectivity while retaining highly potent antitumor efficacy. For example, bispecific ADCs directed against c-MET and EGFR displayed efficacious killing of EGFR and c-MET overexpressing cancer cells with reduced toxicity in normal cells expressing EGFR.

The mechanism of action of bispecific ADCs.Fig.2 The process of bispecific ADCs exerting activity.

Our Service

Bispecific ADCs Development Services

Several bispecific ADC approaches have been developed by Creative Biolabs to enhance internalization and trafficking to the lysosome, thus maximizing the amount of drug that is effectively delivered to tumor cells at a given dose.

This approach consists of utilizing one arm of the bispecific to target an existing fast internalizing receptor that promotes trafficking to lysosome and degradation of the complex, whilst the second arm is used to enable specific binding to the surface of the target tumor cell. This approach alleviates the need to focus solely on internalizing and non-fast-recycling targets for cancer therapy but still requires the presence of a strongly internalizing target on the cell surface to "drag"> the other antigen and transfer it to the lysosome. For example, the bispecific ADCs simultaneously targets the HER2 and PRLR double positive breast cancer cells to enhance the internalization and activity of the ADC, and to decrease the off-target toxicities to the healthy cells.

Another and more general approach to increase internalization and trafficking to the lysosomes consists of simultaneously targeting two different epitopes on the same antigen with a bispecific entity (e.g. a biparatopic antibody). This can not only increase selectivity towards cancer cells but it can also lead to enhanced internalization and trafficking to the lysosome by inducing clustering and cross-linking of receptors. The past few years have seen an increase in the development of biparatopic platforms to promote receptor lysosomal trafficking; this approach is now also gathering momentum in the ADC field. For example, an anti-HER2 biparatopic antibody displayed better internalization, lysosomal trafficking, and degradation of the antibody-antigen complex relative to the traditional T-DM1.

At Creative Biolabs, we can offer the following bispecific ADCs development services:

1. Selection of epitope/receptor combinations: fast-internalizing receptor, biparatopic receptor

2. Identification of bispecific antibody formats: bivalent bispecific antibodies, tetravalent multispecific antibodies

3. Generation of bispecific ADC

4. In vitro and in vivo evaluation of bispecific ADC

Creative Biolabs has been involved in the development of ADCs for many years and we are committed to completing your project with high quality. We can provide you with the best services to ensure your requirements are met. If you are interested in our bispecific ADCs development services, please contact us for more details.

Highlights

  • Enhanced Drug Selectivity and Efficacy: Combining bsAbs with ADCs, Creative Biolabs' bispecific ADCs development services improve cancer treatment selectivity and efficacy, minimizing off-target effects and enhancing therapeutic outcomes.
  • Optimized Internalization and Payload Delivery: Our bispecific ADCs ensure efficient internalization and lysosomal routing, maximizing drug delivery to tumor cells and enhancing the therapeutic impact of cytotoxic drugs.
  • Customized Bispecific ADC Development: Creative Biolabs offers tailored bispecific ADC development, selecting optimal epitope/receptor combinations and antibody formats to meet specific project requirements and achieve superior outcomes.
  • Advanced Evaluation and Optimization: We provide comprehensive in vitro and in vivo evaluation of bispecific ADCs, ensuring they meet high standards of efficacy and safety, enhancing therapeutic and drug development projects.
  • Expertise and Commitment to Quality: With extensive ADC development experience, Creative Biolabs ensures high-quality bispecific ADC services, delivering innovative solutions to meet research and therapeutic goals. Contact us for details.

FAQ

  1. Q: What are bispecific ADCs and how do they enhance cancer treatment?

    A: Bispecific antibody-drug conjugates (ADCs) are advanced therapeutics that combine the targeting capabilities of bispecific antibodies with the cytotoxic potency of ADCs. These molecules improve cancer treatment by enhancing drug selectivity, internalization, and payload delivery efficiency, resulting in more effective tumor cell targeting and reduced off-target effects.

  2. Q: How does Creative Biolabs optimize bispecific ADCs for enhanced efficacy?

    A: Creative Biolabs leverages its well-established ADC and bispecific antibody (bsAb) platforms to develop customized bispecific ADCs. This involves optimizing antibody affinity, selectivity, and pharmacokinetics to ensure high tumor specificity and effective payload delivery, ultimately improving therapeutic outcomes.

  3. Q: What are the advantages of using fast-internalizing receptor-based bispecific ADCs?

    A: Fast-internalizing receptor-based bispecific ADCs utilize one antibody arm to target a receptor that rapidly internalizes and promotes lysosomal trafficking, while the other arm ensures specific binding to the tumor cell. This approach maximizes drug delivery to tumor cells, enhancing therapeutic efficacy while minimizing off-target toxicities.

  4. Q: What services does Creative Biolabs offer for bispecific ADCs development?

    A: Creative Biolabs provides comprehensive bispecific ADCs development services, including the selection of epitope/receptor combinations, identification of bispecific antibody formats (bivalent or tetravalent), generation of bispecific ADCs, and in vitro and in vivo evaluation of their efficacy and safety.

  5. Q: What makes Creative Biolabs a reliable partner for bispecific ADCs development?

    A: With years of experience in ADC development, Creative Biolabs is committed to providing high-quality, customized services tailored to meet client needs. Their expertise in bispecific antibody and ADC platforms ensures that projects are completed with precision and efficacy, resulting in optimal therapeutic candidates.

Published Data

The study highlights the role of bispecific antibody-drug conjugates (ADCs) in improving the efficacy of HER2 ADCs by targeting both HER2 and the prolactin receptor (PRLR). The bispecific ADCs bridge HER2 and PRLR, which leads to enhanced internalization and degradation of HER2 through lysosomal pathways, thereby increasing the cytotoxic effect on breast cancer cells. The bispecific ADCs demonstrated more effective cell killing in breast cancer cells co-expressing HER2 and PRLR compared to HER2 ADC alone. This approach addresses the limitation of HER2 ADCs in targeting cells with low to moderate HER2 expression, showcasing a significant improvement in therapeutic outcomes for such cancer cell populations.

In vitro cell killing evaluation of bispecific antibody targeting HER2 and PRLR.Fig.2 Low levels of surface PRLR, but not HER2, are sufficient to mediate ADC cell killing in vitro.1

Featured Products

Anti-MET ADC

Catalog Product Name Antibody
ADC-W-1543 Anti-MET (Onartuzumab)-MC-Vc-PAB-DMEA-(PEG2)-duocarmycin SA ADC Humanized Anti-MET IgG1 monovalent antibody, Onartuzumab
ADC-W-2372 Anti-MET (Emibetuzumab)-SMCC-DM1 ADC Humanized Anti-MET IgG4-kappa antibody, Emibetuzumab
ADC-W-2373 Anti-MET (Emibetuzumab)-SPDB-DM4 ADC Humanized Anti-MET IgG4-kappa antibody, Emibetuzumab
ADC-W-2374 Anti-MET (Emibetuzumab)-MC-MMAF ADC Humanized Anti-MET IgG4-kappa antibody, Emibetuzumab
ADC-W-2375 Anti-MET (Emibetuzumab)-MC-Vc-PAB-MMAE ADC Humanized Anti-MET IgG4-kappa antibody, Emibetuzumab

Anti-EGFR ADC

Catalog Product Name Antibody
ADC-W-013 Anti-EGFR-Mc-VC-PABC-MMAE ADC humanized Anti-EGFR Antibody
ADC-W-015 Anti-EGFR-Mc-MMAF ADC Humanized Anti-EGFR Antibody
ADC-W-035 Anti-EGFR (clone A1)-Mc-MMAF ADC Humanized Anti-EGFR antibody, clone # Antibody 1
ADC-W-126 Anti-EGFR (clone Bat0206)-S-3AA-MDC ADC Anti-EGFR antibody, clone # Bat0206
ADC-W-127 Anti-EGFR (clone Bat0206)-SMCC-MDC ADC Anti-EGFR antibody, clone # Bat0206

Reference

  1. Andreev, Julian, et al. "Bispecific antibodies and antibody–drug conjugates (ADCs) bridging HER2 and prolactin receptor improve efficacy of HER2 ADCs." Molecular cancer therapeutics 16.4 (2017): 681-693.

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