Cancer

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The National Institute for Biotechnology
in the Negev Ltd.
Ben-Gurion University of the Negev

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Research Field

Prof. Porgador studies innate immunity in health and disease. In much broader terms, he also investigates prolongation of protein lifespan in a host and the direct killing of tumor cells.

Understanding that cancers grow by suppressing the immune system, Prof. Porgador and his team work on checkpoint antibodies. Normally, these checkpoints prevent the immune system from attacking the host “self” cells by ensuring that the immune response is activated only against pathogens or against cells that are destined to be destroyed. If correct control over these checkpoints is lost autoimmunity and other pathologies, including cancer, can occur. A successful cancer not only suppresses the immune system but also subjugates it to make the system work for the cancer using these checkpoints. Cancers express ligands or cause other immune cells to express ligands that interact with suppressor-type immuno-receptors that are on immune cells, and activate them to suppress. The reaction between the ligand and these types of immuno-receptors is the checkpoint, suppressing T cells, NK (natural killer) cells, and other immune cells. Therefore, if this can be understood, the researchers can generate an antibody that interferes with the interaction between the ligand and this type of immuno-receptor. An antibody then suppresses the immune suppression caused by the cancer, resulting in ‘enhancement,’ which is essentially normal functioning. Injecting the antibody leads to toxicity due to suppression of this activity elsewhere in body, acting as a new immunotherapy against cancer.

Prof. Porgador and his colleagues explore any applicative inspiration they get from the immune system. For example, they realized that part of a sequence can be used to directly bind to a cancer protein and affect the cancer without any connection to the immune system. The cancer protein is expressed in the nucleus and involved in proliferation and the cell cycle, but binding to the protein interferes with function and induces apoptosis. With this knowledge, the researchers will design a chimeric protein containing the sequence needed to penetrate the cell and reach the nucleus fused to the peptide domain targeting the protein of interest.

The team also looks at life prolongation of proteins in a host. Some short-lived proteins are used as drugs, however because of their short lifespan they must be taken frequently. For example, children that require growth hormone – a market valued at around $3 billion per year – must receive daily injections for a number of years, which is an extremely unpleasant experience. If the protein can be modified, using an unrelated genetic sequence that has been isolated from the immune system, it might be possible to reduce the frequency of the injections, for example from 365 per year to 52(weekly injection) or 12 (monthly injection).

Prof. Angel Porgador

Prof. Porgador is interested in the innate immune system which acts as the first line of defense against infections. His research is broad, frequently taking inspiration from the immune system into another setting. For example, he seeks to prolong the life of proteins, such as human growth hormone, in order to reduce the frequency that children with growth deficiencies need to take these supplements (currently, daily administration is required). Among other topics, he is also working to understand how some diseases, such as cancer, are able to commandeer the immune system to avoid destruction, and in doing so he aims to find new ways for the immune system to target cancers.

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