Applications of bispecific antibodies in therapeutics

The therapeutic applications of bispecific antibodies (bsAbs) span various fields, including oncology, hematology, and ophthalmology. With several FDA-approved bsAbs already in clinical use^​1​, their impact on modern medicine is profound and growing.

This article will discuss the mechanisms of action of bsAbs, their current and emerging therapeutic applications, and the future prospects of these groundbreaking agents, highlighting their transformative potential in healthcare.

Bispecific antibodies – mechanisms of action

One of the primary mechanisms by which bsAbs operate is by recruiting immune cells, such as effector T-cells, directly to tumor cells. This is accomplished through the bispecific nature of these antibodies, with one binding site targeting a specific antigen on the tumor cell and the other binding site targeting an antigen on the T-cell, such as CD3.

This proximity enables the immune cells to exert their cytotoxic effects directly on the tumor cells, enhancing the immune response and promoting tumor cell destruction (through mechanisms like antibody-dependent cellular cytotoxicity [ADCC]).

Another significant mechanism of action for bsAbs is the blocking of signaling pathways that are critical for the survival and proliferation of cancer cells. A dual blockade can halt the growth of cancer cells more efficiently than targeting a single receptor, as it addresses redundancy within the cancer cell’s signaling network.

In addition to targeting tumor cells and blocking signaling pathways, bsAbs can also block cytokine signaling. Cytokines are small proteins that play key roles in cell signaling. Inflammatory cytokines are often involved in the progression of autoimmune diseases and chronic inflammatory conditions. By simultaneously neutralizing multiple cytokines or their receptors, bsAbs can significantly reduce inflammation and alter the course of these diseases.^​2​ This cytokine-blocking ability is particularly beneficial in conditions where multiple cytokines are contributing to the pathology, providing a more comprehensive therapeutic approach.

The production of bsAbs involves advanced recombinant DNA technology, allowing for the precise design and manufacture of antibodies with specific characteristics. Techniques such as transient or stable transfection in cell lines such as Chinese hamster ovary cells (CHO cells) are employed to produce high-quality bsAbs at scale. This ensures that bsAbs are not only effective but also reliable and consistent in their performance.

Fields of applications of bsAbs in therapeutics – examples

Bispecific antibodies differ from traditional monoclonal antibodies (mAbs) by targeting two antigens simultaneously. Their dual-targeting ability expands their applications across various fields of medicine, enhancing treatment efficacy and patient outcomes.

Oncology

BsAbs are transforming oncology as they can simultaneously bind to antigens on both tumor cells and immune cells, facilitating direct immune attacks. This mechanism can not only improve the targeting accuracy of the immune response but also amplify it and help overcome therapeutic resistance, leading to more effective tumor cell destruction.

One example of bsAb approved for oncologic treatment is Blinatumomab (Blincyto®), which is used in treating acute lymphoblastic leukemia (ALL) by binding to CD19 present on the cancerous B cells and to CD3 on T-cells, thereby promoting targeted cytotoxicity.^​3​

Hematology

BsAbs have made significant strides in hematology, particularly in the treatment of hemophilia. Hemophilia is a genetic disorder characterized by the inability to properly form blood clots due to the deficiency of specific clotting factors. 

Emicizumab (Hemlibra®) is a groundbreaking FDA-approved antibody that has transformed hemophilia A treatment. It bridges activated Factor IX and Factor X, mimicking the function of the missing Factor VIII, thereby facilitating proper blood clotting. The innovative approach of Hemlibra® reduces the frequency of bleeding episodes and improves the quality of life for patients with hemophilia A.^​4​

Ophthalmology

BsAbs are also making significant advancements in ophthalmology, providing innovative solutions for treating complex eye diseases. Faricimab (Vabysmo®) is a pioneering bsAb developed for ocular conditions such as neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).

By simultaneously inhibiting VEGF-A and Angiopoietin-2, Faricimab addresses the primary factors involved in abnormal blood vessel formation and vascular permeability, which are key contributors to these conditions. This targeted therapy not only helps in reducing disease progression but also extends the intervals between treatments, significantly easing the burden on patients.^​5​

Faricimab represents a new era in ophthalmic treatment, offering effective and long-lasting results, ultimately aiming to preserve vision and enhance quality of life for patients with serious retinal diseases.

Diagnostics

BsAbs are finding significant applications beyond their established therapeutic roles, too. In diagnostics, bsAbs offer enhanced sensitivity and specificity for detecting biomarkers associated with various diseases.

For instance, bsAbs can be engineered to detect two different biomarkers simultaneously, improving the accuracy of diagnostic tests. This, for instance, is particularly useful in the early detection of cancer.^​6​

Perspective: What to expect from bsAbs in the future

The future of bsAbs is promising, with research expanding into new therapeutic areas such as vascular and neurodegenerative disorders, infectious and autoimmune diseases. Another promising field of application is the use of bsAbs in chronic inflammatory diseases, as well as hematology. The largest share of bsAbs currently being developed, however, is aimed to drive progress in cancer treatment. As of March 2024, more than 200 bispecifics are currently in clinical development.^​1​

The production of bsAbs for research and diagnostics also benefits from advancements in recombinant DNA technology and antibody production in CHO cells. Techniques such as transient transfection and stable transfection ensure the efficient and scalable production of high-quality bsAbs, supporting their widespread use in various applications. Companies like evitria offer specialized bispecific antibody expression services, enabling researchers, pharmaceutical companies and CDMOs to access customized bsAbs tailored to their specific needs.^​7​

evitria – providing bsAbs for multiple applications

evitria is a leading provider of bispecific antibody production services, supporting a wide range of applications in both therapeutic and research settings. Leveraging their expertise in recombinant DNA technology and state-of-the-art production techniques, evitria offers customized bsAb solutions tailored to specific needs. Our advanced production methods, including transient transfection in CHO cells, ensure high yields and quality of bispecific antibodies.

evitria excels in delivering bsAbs for various therapeutic fields such as oncology, hematology, and ophthalmology. By producing even complex bispecific formats like CrossMab, IgG-scFvs, or Knobs-into-Hole, we enable researchers and pharmaceutical companies to explore innovative treatment options for challenging diseases.

But not only do we produce bsAbs – we also help our customers to individualize which specific bsAb is best suited for their unique requirements. By partnering with evitria, partners worldwide benefit from our extensive experience and rapid expression times (from sequence to antibody in 4 weeks!), as they drive forward the potential of bsAbs in transforming healthcare and scientific research.