Every one of us was born with an immune system that acts like the security checkpoint at the airport. This high-tech scanner system inside the human body identifies what kind of antibodies we need to protect us from foreign invaders.  

What keeps our bodies healthy

Antibodies are Y-shaped proteins which are produced by the immune system to neutralise pathogens such as bacteria and viruses. When such a pathogen enters our body, it stimulates the immune system to produce antibodies that recognise a unique molecule of the harmful agent, called an antigen, and binds to it with precision. This binding may stop the biological process causing the disease or may activate macrophages or natural killer cells to destroy the foreign substance.

Understanding antibody response is also central to develop blood tests to diagnose diseases. Imagine you are a doctor and a patient comes to see you with symptoms of an autoimmune disease, which needs to be treated. To make a correct diagnosis the doctor needs to know what type of antibodies the patient’s body is producing.

Designing complex antibodies

A classical antibody’s two arms will bind specifically to one antigen. Expertise in molecular design has led to novel antibody formats with additional features. One approach implies engineering multiple antigen binding domains into a single antibody molecule. These so-called bi-or multispecific antibodies combine two or more antigen-recognising elements into a single molecule, able to bind to two or more targets.

At Roche, we have designed a new format for bispecific antibodies, called CrossMAbs. In contrast to other technologies, the CrossMAb allows production and correct chain assembly using a standard process applied for the production of therapeutic antibodies.

The acquisition of Dutalys in 2014 strengthens our capabilities in the discovery and development of fully human, bi-specific antibodies based on the proprietary DutaMabs™ technology. The DutaMab™ technology platform further enables the development of bi-specific antibodies on a single arm of the antibody while still displaying good manufacturing properties.

We currently have several different therapeutic antibody formats in early clinical development for different indications. In the future, these could hopefully play an important role in addressing the complexity of targeting diseases with unmet medical need.

Therapeutic antibodies at Roche – a gallery of selected players:

  • The Brain-Shuttle Technology boosts the uptake of large molecule therapeutics into the brain.
    The Brain-Shuttle Technology boosts the uptake of large molecule therapeutics into the brain.
  • A DutaFab can bind two antigens, while in an IgG format a DutaMab can bind up to 2x2 antigens.
    A DutaFab can bind two antigens, while in an IgG format a DutaMab can bind up to 2x2 antigens.
  • The bispecific CrossMAb can be produced using standard infrastructure.
    The bispecific CrossMAb can be produced using standard infrastructure.
  • Antibody cytokine fusion proteins stimulate the immune system with high specificity and tolerability.
    Antibody cytokine fusion proteins stimulate the immune system with high specificity and tolerability.
  • This antibody has a third arm designed to hook to T cells, bringing them in close proximity to the cancer cells. The T-cell then attacks the cancer cell.
    This antibody has a third arm designed to hook to T cells, bringing them in close proximity to the cancer cells. The T-cell then attacks the cancer cell.
  • The glycoengineered antibody is a potent killer of cancer cells it is targeted to.
    The glycoengineered antibody is a potent killer of cancer cells it is targeted to.

As our understanding of biology increases, we continue to gain a better understanding of what features will make a therapeutic antibody more effective. Our scientists are at the forefront in antibody engineering and constantly improving and inventing the next generation of molecules.

Today we are breaking all the rules of what a therapeutic protein modality should look like. It is exciting to see how these innovations allow us revolutionary modes of actions.
Pearl S Huang - Head of Therapeutic Modalities

From discovery to application

The concept of “antibodies” was first introduced by Paul Ehrlich’s publication, ‘Experimental Studies on Immunity’ in 1891. He based his work on the idea that the chemical constitution of drugs must be studied in relation to their mode of action. His aim was to find chemical substances which have special affinities for pathogenic organisms. Ehrlich called these “magic bullets” as they were targeting a pathogen. In 1908 Ehrlich received the Nobel Prize.

Thirty years ago, George Köhler and César Milstein – scientists at the Roche-funded Basel Institute for Immunology – invented the technology to produce monoclonal antibodies from hybridoma cells and won the Nobel Prize for it in 1984.

Since then monoclonal antibodies revolutionised biological research and built the basis across the entire biotechnology industry for the use of antibodies as therapeutics as well as for diagnostic applications.

Therapeutic antibodies have improved treatments of complex diseases such as cancer, viral infections and inflammatory diseases over the past three decades, due to their unique ability to specifically home in on surface proteins.

Today, new generations of biologically engineered antibody drugs are emerging, enabling a strong shift from discovery and production of standard monoclonal antibodies to highly complex formats.

Tags: Science