ImmunoBodies ™

Antibodies bind selectively to specific antigen molecules on the surface of pathogens, making them more visible to the immune system. Antigen-antibody complexes stimulate the immune system in a number of ways.

• The complex can bind to phagocytic cells, triggering efficient pathogen digestion.
• The antibody-antigen interaction can efficiently present antigen on the cell surface to stimulate the various T-cell responses that control and maintain the response against the pathogen.
• When the complex binds to dendritic cells (highly specialized Antigen Presenting Cells), efficient processing and presentation of antigen loaded onto MHC molecules stimulates both the helper and cytotoxic T-cells (CTLs).

ImmunoBodies™ are unique, patent protected, recombinant proteins that incorporate the antigen/antibody complex in a single molecule. They comprise two components: the constant region of a human IgG1 immunoglobulin that binds to the CD64 (FcgR1) receptor on dendritic cells, and a polypeptide that is processed by the dendritic cells and presented on specialised molecules (MHC antigens) to stimulate both killer and helper T cells. Killer T cells are the most efficient cells in the body for finding and killing either infected or cancerous cells. Helper T-cells also find infected or cancer cells and release a variety of cytokines that are directly cytotoxic and that can aid in the recruitment of killer T cells, natural killer cells and tumoricidal macrophages.

Vaccines are often designed to stimulate neutralising antibodies that bind to specific pathogens and prevent disease. However some viruses are particularly effective at avoiding the immune response and develop into chronic infections. Therapeutic vaccines have tended to fail because they:

• Only stimulate a single component of the immune response, either cytotoxic T cells, helper T cells or antibodies.
• Target a single protein which can mutate, making the disease resistant to the vaccine.

The ImmunoBody™ technology overcomes these limitations by stimulating cytotoxic T cells, helper T cells and antibodies and can target multiple proteins within a single vaccination.

Major advances in the approaches include:

• The ability to address pathogens where key target antigens(s) are identified but are only weakly immunogenic in the absence of the Fc addition, to enable appropriate targeting and binding.
• Rapid development of a vaccine when a new antigen is identified, for example in pandemic influenza or in response to bioterrorism.
• Potential to incorporate multiple antigens.
• A defined manufacturing and regulatory path, reducing development risk, time and cost.
• Multiple manufacturing options, in different expression systems, providing fast manufacture production and low cost of goods.

ImmBio works with contract manufacturers to design, scale up and supply material. Depending on specific circumstances, both insect and mammalian expression systems are used.

The basic science behind ImmunoBodies

The human body is equipped with a powerful and sophisticated system of defence against harmful pathogens - the immune system. The proper functioning of the immune response to invading pathogens is prompt, appropriate and self-limiting. It also retains a "memory" of pathogens encountered, enabling more rapid responses to future invasion. Consequently a number of vaccines are already available, each of which builds a specific defence capability, through mechanisms which mimic (but not replicate) infection, ahead of any potential contact with the relevant matching pathogen.

The immune response is essentially composed of two phases:

• An initial ‘innate’ response that is a generalised, fast response to any pathogen.
• A subsequent ‘adaptive’ response that is specific to the invading pathogen.

The innate response is mediated by genes that are inherited in the germ line and is typified by inflammation. The adaptive response is mediated by genes that are specifically re-arranged in effector cells of the immune system, namely the T and B-lymphocytes, forming pathogen-specific molecules (e.g. antibodies produced by B-cells). Until recently, knowledge of the immune system has almost exclusively been around the pathogen-specific adaptive immune response. However, the key role of the innate response in the control of the adaptive phase is now being appreciated and is the basis of the evolution of ‘immunology’ into the emerging science of ‘immunobiology’.

The primary adaptive response is elicited when the immune system is exposed to a pathogen for the first time. In the terminal phase of the primary response, antibodies that recognise the pathogen are made and selectively modified to improve their affinity for the pathogen antigens so they can be used to efficiently neutralise and capture the pathogen in any subsequent encounter (a secondary adaptive response). The complex of antibody and pathogen (immune complex) is used by antigen-presenting cells (APCs) such as the dendritic cell (DC) to capture pathogen antigens through the binding of the tails of the antibody molecules (Fc-domains) to specific receptors (FcR) that are present on the cell surface of these cells. Captured antigens are then processed into peptides which are loaded onto molecules of the major histocompatibility complex (MHC) to active antigen-specific T-cells.

The diagram above sets out the key stages in an immunological response, described in the following narration:

1. ImmunoBody™ binds to the Fc receptor on dendritic cells
2. Internalisation occurs through cellular pathway
3. Protein cleavage occurs and processing leads to presentation of antigens to immune cells
4. Peptides bind to MHC molecules
5. Immune cells recognise pathogen’s antigens and kill.

ImmunoBodies™ patents and trade mark is owned by Scancell Ltd, a company focused on oncology. ImmBio holds a license for their use against specific anti-infective targets.