John McCafferty

John McCafferty was a co-founder of Cambridge Antibody Technology (CAT, acquired by Astra Zeneca). There he was a co-inventor of antibody phage display, the subject of the 2018 Nobel Prize in Chemistry awarded to his co-inventor Greg Winter. Phage display technology is used worldwide and has yielded multiple approved antibodies including the world’s biggest selling drug Humira, which was created at CAT. He also founded another antibody discovery company IONTAS and more recently he formed Maxion Therapeutics.

Biography

McCafferty is currently an Affiliated professor in the Department of Medicine and CITIID. His group seeks to tackle the scourge of snakebite envenomation, which kills 100,000 people annually and causes debilitating injury to hundreds of thousands more. The group are applying recombinant antibody technology to generate venom-neutralising recombinant antibodies.

Despite much effort by biotechnologists over the last 3 decades, creation of ion channel-blocking antibodies has proven difficult. In contrast, nature has created small cysteine-rich peptides (knottins) as ion channel-modulating components of venoms. Knottins however do not make good drugs suffering from manufacturing difficulties, short half-lives and a lack of specificity.

In order to overcome these challenges, Dr McCafferty has developed a novel molecular format (a KnotBody^TM) wherein a surface loop of an antibody is replaced by a knottin. This results in a fusion molecule combining the best of both worlds with the ion channel blockade of the knottin and the benefits of an antibody (i.e. long half-life, standard manufacturing and potential for engineering improved specificity and potency using phage display and mammalian display technologies).

Maxion’s lead programme addresses auto-immunity by targetting a voltage-gated channel (Kv1.3) used by a subset of auto-reactive T cells.

Research

His recently formed academic group at the Department of Medicine seeks to bring this long experience in recombinant antibody technology to bear on the problems of developing world and in particular the scourge of snakebite envenomation.

Snakebite envenomation kills 100,000 peopl/year and causes debilitating injury to 100,000's more victims. The main therapeutic intervention for snakebite envenomation relies on the century-old approach of injecting victims with animal-derived polyclonal antiserum. Animal immunisation generates high affinity antibodies and undoubtedly saves lives, but the use of immune antiserum has a number of limitations around consistency, redundancy and immunogenicity.

Working in collaboration with Institut Clomido Picado, Costa Rica (an anti-venom producer) the group will use recombinant antibody technology towards the capture, sequencing an characterisation of the antibody repertoire arising from venom immunisation to create a defined, oligoclonal chimeric antibody cocktail.

Publications

Key publications:

Michael R. Dyson, Edward Masters, Deividas Pazeraitis, Rajika L. Perera, Johanna L. Syrjanen, Sachin Surade, Nels Thorsteinson, Kothai Parthiban, Philip C. Jones, Maheen Sattar, Gordana Wozniak-Knopp, Florian Rueker, Rachael Leah, John McCafferty (2020) Beyond affinity: selection of antibody variants with optimal biophysical properties and reduced immunogenicity from mammalian display libraries mAbs 12(1):1829335, DOI: 10.1080/19420862.2020.1829335

Kothai Parthiban, Rajika L. Perera, Maheen Sattar, Yanchao Huang, Sophie Mayle, Edward Masters, Daniel Griffiths, Sachin Surade, Rachael Leah, Michael R. Dyson, John McCafferty (2019) A comprehensive search of functional sequence space using large mammalian display libraries created by gene editing mAbs 11:5, 884-898 https://doi.org/10.1080/19420862.2019.1618673

Subject:

antibodies

Biography

Research

Publications

Affiliations

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