Advances in immuno-oncology (IO) are revolutionising the standard of care for many types of cancer says a report by the US Cancer Research Institute published in the Annals of Oncology.

As of September 2017, 26 immunotherapies have been approved in the USA, and 17 types of cancer have at least one approved immunotherapy as a treatment option, the report says.

The first approval of modern cancer immunotherapy was interferon-a in 1986 for hairy cell leukaemia, and later for chronic myelogenous leukaemia, follicular non-Hodgkin lymphoma, melanoma, and AIDS-related Kaposi’s sarcoma.

Several other agents have been approved since then, but a transformation in the landscape of IO started with the approval of ipilimumab for advanced melanoma in 2011. Ipilimumab is a checkpoint inhibitor which targets CTLA-4. CTLA-4 is an immunoglobulin that is expressed by activated T cells and transmits an inhibitory signal to T cells.

In the past three years alone, five new inhibitors targeting checkpoint proteins on immune cells have been approved. These novel immunotherapies in most cases are designed to treat advanced, refractory, or relapsed cancers that did not respond to standard cancer treatments, the report says.

Since the approval of ipilimumab, the pipeline of IO agents in clinical and preclinical development has become crowded. As of September 2017, there were 940 IO agents from 462 different companies or academic institutes in clinical trials, with another 1,064 in preclinical phase. The report classifies the agents in clinical development into six groups:

  • T-cell-targeted immune-modulators that act on inhibitory or activating molecules expressed by T cells
  • Other immune-modulators that act on other immune cells to unleash antitumour immunity
  • Cancer vaccines that induce antigen- specific anti-tumour immunity
  • Cell therapies that engineer immune cells such as T cells to directly attack cancer cells
  • Oncolytic viruses that rely on both direct tumour killing and activation of antitumour immunity
  • CD3-targeted bispecific antibodies that bring T cells to the targeted tumour cells for direct killing.

There is significant duplication of mode of action among the agents. There are some 3,042 interventional active clinical trials evaluating the clinical-stage immunotherapies with a target of enrolling over 577,000 patients.

This leads the report’s authors to suggest that the concentration of IO development and patient resources on a few targets, some with already approved drugs, could potentially be stalling future innovation.

 

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