TIM-3 based Bispecific ADC Development Service

As a novel targeted therapy for cancers, bispecific antibody-drug conjugates (ADCs) are displaying great potential and promising. Serval bispecific ADCs against different targets are developed actively in recent years, which need high-quality material such as bispecific antibody and linker-payload. Creative Biolabs is a leader in the field of antibody production and bio-conjugation for more than ten years, we offer a full range of bispecific ADCs design and construction services, from materials preparation to final product characterization.

Background

The Overview of TIM-3

T cell immunoglobulin mucin-(TIM)-3 was identified as a molecule specifically expressed on IFN-γ-secreting CD4+ T helper 1 (Th1) and CD8+ T cytotoxic (Tc1) cells in both mice and humans. The specific expression of TIM-3 on Th1 cells catalyzed investigation into its potential role as a regulator of Th1 cells. TIM-3 acts as a negative regulator of Th1/Tc1 cell function by triggering cell death upon interaction with its ligand, galectin-9. Indeed, targeting the Tim-3 pathway has shown very promising results in human diseases.

Human TIM-3 is a 302 amino acid (aa) type I transmembrane glycoprotein that contains a membrane distal immunoglobulin variable (IgV) domain and a membrane proximal mucin domain. TIM-3 belongs to the immunoglobulin superfamily (IgSF) and recent studies have revealed the 3D structure of the IgV domain of TIM-3.TIM-3 IgV domains consist of two anti-parallel β sheets that are tethered by a disulfide bond. Additional two disulfide bonds are formed by four noncanonical cysteines that are invariant within TIM proteins and unique among IgSF members. They stabilize the IgV domain of TIM-3 and reorient the CC’ loop so that it is close to the FG loop, resulting in the formation of a “cleft” or “pocket” structure in TIM-3 as well as other TIM proteins. This unique cleft structure is not found in other IgSF proteins and has been predicted to be involved in ligand binding.

Fig.1 Models for TIM-3-ligand interactions.¹

Antibodies-based Therapeutics Targeting TIM-3

Immune cells that express TIM-3 promote immune tolerance to tumors and thus therapeutic antibodies that target TIM-3 have been developed and tested for various cancer therapy. Studies in multiple animal models have shown that antibody-mediated TIM-3 inhibition enhances the activity of immune checkpoint blockade. Combining anti-TIM-3 with anti-PD-1 therapy might be a viable option to overcome T-cell exhaustion in patients and promote responses to immune checkpoint blockade. In addition, antibodies against TIM-3 are being investigated in multiple clinical trials.

NCT03680508 is a phase II trial, testing anti-TIM-3 mAb TSR-022 in combination with anti-PD-1 mAb TSR-042 in patients with hepatocellular carcinoma. Early data suggests that blocking TIM-3 enhances cytotoxic T-cell-mediated tumor lysis.

Patent EP3356411A1 describes a method by producing anti-TIM3/anti-PD-1 bispecific antibodies and their potential in cancer treatment. These data are in line with data in preclinical models showing the superior efficacy of TIM3 pathway and PD1 pathway co- blockade over single- agent treatments.

RO7121661 is a bispecific antibody targeting PD-1 and TIM-3 simultaneously. It was developed by Roche and a phase I dose-escalation and expansion study has been ongoing on advanced solid tumors.

Our Service

TIM-3-based Bispecific ADCs Services

With years of experience and plenty of researches, scientists from Creative Biolabs have investigated and established a series of approaches for bispecific ADC production. We have constructed different epitope combinations for TIM-3-based bispecific ADCs development, such as TIM-3 x PD-1 and TIM-3 x LAG-3. If you are interested in our services, please contact us for more details.

Highlights

• Leading expertise in bispecific ADC development: Creative Biolabs specializes in designing and constructing TIM-3-based bispecific ADCs, offering expertise in antibody production, bio-conjugation, and high-quality linker-payload materials.
• End-to-end bispecific ADC development: With over ten years of experience, Creative Biolabs provides comprehensive bispecific ADCs services, including materials preparation, epitope combinations, and final product characterization.
• Innovative approaches to cancer therapy: Creative Biolabs leverages innovative technology to develop TIM-3-based bispecific ADCs, targeting immune checkpoints like PD-1 and LAG-3, with the potential for enhanced cancer treatment.
• Tailored solutions for bispecific ADCs: Creative Biolabs offers full-scale production services for bispecific ADCs, focusing on combining TIM-3 with PD-1 or LAG-3 to optimize cancer immunotherapy outcomes.
• Advanced bio-conjugation technologies: Creative Biolabs utilizes advanced bio-conjugation techniques to create TIM-3-based bispecific ADCs, ensuring superior stability, efficacy, and ligand-binding capability in therapeutic applications.

FAQ

1. Q: What are the main advantages of TIM-3-based bispecific ADCs for cancer treatment?

   A: TIM-3-based bispecific ADCs offer a dual-target approach to enhancing the immune response against cancer. By targeting TIM-3 and other immune checkpoint molecules like PD-1, these ADCs improve T-cell function and reduce immune tolerance, leading to enhanced tumor elimination.

2. Q: What makes TIM-3 an ideal target for bispecific ADC development?

   A: TIM-3 is expressed on IFN-γ-secreting CD4+ Th1 and CD8+ Tc1 cells, acting as a negative regulator. By inhibiting TIM-3, bispecific ADCs can reverse T-cell exhaustion and promote stronger anti-tumor immune responses, which is particularly useful in cancer immunotherapy.

3. Q: How does Creative Biolabs support the development of TIM-3-based bispecific ADCs?

   A: Creative Biolabs provides comprehensive bispecific ADC development services, from materials preparation, including bispecific antibodies and linker-payloads, to final product characterization. Our expertise in bio-conjugation and antibody production ensures high-quality outputs for TIM-3-based bispecific ADCs.

4. Q: Can TIM-3 x PD-1 bispecific ADCs improve the effectiveness of immune checkpoint inhibitors?

   A: Yes, combining TIM-3 with PD-1 in a bispecific ADC can enhance the immune system's ability to combat cancer. Studies have shown that dual targeting with anti-TIM-3 and anti-PD-1 therapies improves the immune response and reduces tumor resistance to checkpoint blockade.

5. Q: What types of linker-payloads are used in TIM-3-based bispecific ADCs developed by Creative Biolabs?

   A: Creative Biolabs uses state-of-the-art linker-payload technology to ensure stable and effective delivery of cytotoxic agents in TIM-3-based bispecific ADCs. These linkers are designed to improve drug conjugation efficiency and therapeutic index, maximizing anti-tumor efficacy.

Featured Products

Anti-79b ADC