ImmunoBodies ™

Antibodies selectively bind 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 with dendritic cells (highly specialized Antigen Presenting Cells), efficient processing of antigen 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 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.

HspCs bridge between the innate and adaptive response, non-selectively presenting a wide range of antigens. In the course of infection, specific antibodies continue to be raised beyond resolution, conferring a long-lasting protective effect against re-infection. ImmunoBodies™ may therefore be:

• Stand-alone prophylactic and therapeutic vaccines, where there are specific antigens which are protective and where a broad immune response is required.
• Used in combination with HspC, including as a boost, to completely mimic the normal course of infection, successful resolution and protection.

The ImmunoBodies™ platform has been developed by Scancell Ltd. It is progressing a portfolio against cancer. ImmBio has a cross-license agreement with Scancell covering specific pathogens, including a collaborative agreement on improvements, with ImmBio focusing on anti-infective uses.

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

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.

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.