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Development of immuno-oncology drugs — from CTLA4 to PD1 to the next generations

Abstract

Since the regulatory approval of ipilimumab in 2011, the field of cancer immunotherapy has been experiencing a renaissance. This success is based on progress in both preclinical and clinical science, including the development of new methods of investigation. Immuno-oncology has become a sub-specialty within oncology owing to its unique science and its potential for substantial and long-term clinical benefit. Immunotherapy agents do not directly attack the tumour but instead mobilize the immune system — this can be achieved through various approaches that utilize adaptive or innate immunity. Therefore, immuno-oncology drug development encompasses a broad range of agents, including antibodies, peptides, proteins, small molecules, adjuvants, cytokines, oncolytic viruses, bi-specific molecules and cellular therapies. This Perspective summarizes the recent history of cancer immunotherapy, including the factors that led to its success, provides an overview of novel drug-development considerations, summarizes three generations of immunotherapies that have been developed since 2011 and, thus, illustrates the breadth of opportunities these new generations of immunotherapies represent.

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Figure 1: Ipilimumab drug-development milestones.
Figure 2: Three generations of immuno-oncology drugs.
Figure 3: Generation 3: various immuno-oncology modalities.
Figure 4: Key trends defining the future of immuno-oncology.

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Acknowledgements

The author thanks the countless colleagues and collaborators who have contributed to the evolution of the immuno-oncology space and the patients and their families for their bravery in fighting cancer and participating in life-saving research.

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Correspondence to Axel Hoos.

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A.H. is an employee and shareholder of GlaxoSmithKline and Director of the Board and shareholder of Imugene.

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Hoos, A. Development of immuno-oncology drugs — from CTLA4 to PD1 to the next generations. Nat Rev Drug Discov 15, 235–247 (2016). https://doi.org/10.1038/nrd.2015.35

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