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Industry pursues co-stimulatory receptor immunomodulators to treat cancer

Nature Biotechnology volume 31, pages 181–182 (2013)Cite this article

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A Corrigendum to this article was published on 10 June 2013

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Meanwhile, London-based pharma GlaxoSmithKline is increasing its footprint in cancer immunotherapy by in-licensing a panel of preclinical antibodies from the University of Texas MD Anderson Cancer Center, which activate the T-cell co-stimulatory receptor OX40. The deal, disclosed on December 7, 2012, is worth up to $335 million in upfront and milestone payments, plus sales royalties should any products gain approval. It follows an agreement the company entered in 2010 with Amplimmune, of Rockville, Maryland, on a programmed cell death-1 (PD-1) inhibitor, AMP-224, which is currently in phase 1 testing. Other recent deals targeting co-receptors include an alliance AstraZeneca of London entered last October with two not-for-profit organizations, the Ludwig Institute for Cancer Research (LICR) and the Cancer Research Institute, both of New York, and a separate collaboration involving the LICR, its Brazilian affiliate, Recepta Biopharma, of Sao Paulo, and Swiss biotech firm 4-Antibody of Basel. These collaborations all provide additional impetus to an area that has—after decades of basic research—finally started to deliver in the clinic. The field now faces the twin challenges of achieving responses in a greater percentage of patients than it has managed to do so far, while ensuring that these biologically powerful therapies can be deployed safely.

The basic goal of cancer immunotherapy is to boost patient immune responses against cancer, either by activating stimulatory co-receptors or by blocking inhibitory co-receptors or immune checkpoints—or, potentially, by a combination of both. (The opposite approach is also being actively explored for treating autoimmune conditions.) Multiple co-receptors and their ligands act as a control mechanism for fine-tuning T-cell regulation during different stages of the immune response. “There are at least ten targets that I think most people are aware of. Biology being what it is, I'm sure there will be others,” says Robert Burns, CEO of 4-Antibody. “It's a highly redundant regulatory system,” agrees Jonathan Skipper, executive director of technology development at the LICR. “What we don't know ultimately is what will be the most effective [co-receptor] to target.” The consortium has not fully characterized the targets it is working on. “We're trying to develop a fast follower program,” says Burns. It has some deep-pocketed rivals for company (Table 1).

Table 1 Selected co-receptor drug discovery & development deals
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Change history

  • 03 May 2013

    In the version of this article initially published, the experimental drug nivolumab was incorrectly designated BMS-936588. The correct designation is BMS-936558. The error has been corrected in the HTML and PDF versions of the article.

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    Cormac Sheridan

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Sheridan, C. Industry pursues co-stimulatory receptor immunomodulators to treat cancer. Nat Biotechnol 31, 181–182 (2013). https://doi.org/10.1038/nbt0313-181

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