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

@article{Hoos2016DevelopmentOI,
  title={Development of immuno-oncology drugs — from CTLA4 to PD1 to the next generations},
  author={Axel Hoos},
  journal={Nature Reviews Drug Discovery},
  year={2016},
  volume={15},
  pages={235-247}
}
  • A. Hoos
  • Published 1 April 2016
  • Biology, Medicine
  • Nature Reviews Drug Discovery
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… 
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References

SHOWING 1-10 OF 172 REFERENCES
Big opportunities for small molecules in immuno-oncology
TLDR
Agents aimed at mechanisms — modulation of the immune response, trafficking to the tumour microenvironment and cellular infiltration — are poised to significantly extend the scope of immuno-oncology applications and enhance the opportunities for combination with tumour-targeted agents and biologic immunotherapies.
Cancer immunotherapy comes of age
TLDR
In the context of advances in the understanding of how tolerance, immunity and immunosuppression regulate antitumour immune responses, these successes suggest that active immunotherapy represents a path to obtain a durable and long-lasting response in cancer patients.
Immune checkpoint inhibitors in melanoma provide the cornerstones for curative therapies.
TLDR
In melanoma anti-CTLA-4 (ipilimumab) was approved in 2011 and anti-PD-1 (pembrolimumab) in 2014 and another anti- PD-1 antibody has been recently approved based on phase III trial results in metastatic melanoma without BRAF mutation.
The immuno-oncology framework
TLDR
This article summarizes the recent lessons for development of agents in the immunotherapy space, describes the systematic creation of a new clinical development paradigm for cancer immunotherapies and integrates this paradigm with the emerging methodological framework for a newclinical sub-specialty of immuno-oncology.
Development of ipilimumab: contribution to a new paradigm for cancer immunotherapy.
Identification of cytotoxic T-lymphocyte antigen-4 (CTLA-4) as a key negative regulator of T-cell activity led to development of the fully human, monoclonal antibody ipilimumab to block CTLA-4 and…
The evolution of checkpoint blockade as a cancer therapy: what's here, what's next?
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
TLDR
Antibody-mediated blockade of PD-L1 induced durable tumor regression and prolonged stabilization of disease in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer.
Immunologic checkpoints blockade in renal cell, prostate, and urothelial malignancies.
TLDR
Encouraging initial data observed in GU cancers with this new class of agents are reported, which have reinforced the interest of investigating the therapeutic potential of the immune checkpoint modulators in large controlled trials.
Cancer immunotherapy
MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer
TLDR
It is demonstrated that tumours expressing PD-L1-positive tumour-infiltrating immune cells had particularly high response rates, and patients with UBC, who are often older and have a higher incidence of renal impairment, may be better able to tolerate MPDL3280A versus chemotherapy.
...
...