New Therapeutic Prevents Cancer Cells Hiding

A new generation immunotherapy, Keytruda, has recently been granted FDA approval. Clinical trials have demonstrated its value in the treatment of advanced melanoma and highlighted it as a breakthrough cancer treatment.

We spoke to Michael Dalrymple, Director Business Development at MRC Technology, to learn more about Keytruda and the role that MRC Technology played in its development.

AM: Can you tell us a little about MRC Technology?

Michael Dalrymple (MD): MRC Technology (MRCT) is an independent medical research charity, which works with organisations within the academic, charity, biotechnology and pharmaceutical sectors globally. MRCT’s core business includes identification of commercially viable basic research,  IP protection/management and translational research to develop diagnostics, small molecules drugs and therapeutic antibodies. MRCT bridges the gap between basic medical research and commercialisation, helping early discoveries progress to clinical application.

MRCT was established 14 years ago to handle the ‘technology transfer’ needs of the UK’s Medical Research Council (MRC). Whilst this remains a major focus today, the majority of our activity is in collaboration with universities, medical research charities, and commercial organisations around the world. MRCT ensures that academic and medical charity partners generate a return on their research investment and provides industry partners with a pipeline of commercially viable projects that ultimately benefit patient health.

AM: Keytruda (pembrolizumab) is a PD-1 therapy – can you explain the principles behind this type of therapy?

MD: Keytruda is a humanised monoclonal antibody, given by injection. As a PD-1 therapy it is one of a new generation of treatments that block the biological pathways cancers use to disguise themselves from the immune system. Use of Keytruda (pembrolizumab) blocks the interaction between the PD-1 receptor and its ligands, PD-L1 and PD-L2, often found on cancer cells. This prevents the cancer cell masking itself from the body’s immune system, making it ‘visible’ to be destroyed.  

AM: What benefits does this type of therapy offer over existing therapies?

MD: Existing, older types of cancer therapies are relatively passive, blocking growth or directly killing cancer cells. A new generation of therapies are aimed at activating the immune system to attack the cancer, potentially giving a more thorough and longer lasting attack.

Figure 1: Routes to cancer immunotherapies

AM: Is the therapy limited to advanced melanoma or is there potential for treatment of other types of cancer?

MD: The therapy also holds great potential for treatment of an array of different cancers, and by the end of 2014 it will be in 24 clinical trials for 30 tumour types, involving an estimated 6,000 patients. In addition to malignant melanoma, phase III clinical trials are progressing for other cancers including previously untreated non-small-cell lung carcinoma (NSCLC) and advanced head, neck and bladder cancers.

AM: Can you tell us about your collaboration with Merck and the role that MRC Technology played in the development of this therapeutic?

MD: UK-based scientists at MRCT, with their extensive expertise in antibody engineering, carried out ‘humanisation’ of a mouse monoclonal antibody. This was an essential step in Keytruda’s development, ensuring that the original antibody could be used in humans without triggering an adverse immune response.

The work was originally carried out by MRCT on behalf of Organon, a pharmaceutical company based in The Netherlands. Organon was acquired by Schering-Plough in 2007 and in 2009 became part of Merck Sharpe Dome.

Michael Dalrymple was speaking to Anna-Marie MacDonald, Editor for Technology Networks.