Cancer immunotherapy: the best is yet to come

Justin Wilson, partner and attorney at Withers & Rodgers, discusses his opinion on the promising innovations in the microbiome and the role of IP in supporting the discovery of new drugs and treatments. 

Harnessing the therapeutic powers of the human microbiome is an exciting area of scientific research which is hoping to unlock the potential of the immune system and improve the efficacy of cancer treatments. But which novel therapeutics and combination therapies will deliver the best patient outcomes?

The successful use of viral vector technology in the development of Oxford-AstraZeneca’s two-dose Covid-19 vaccine has raised public awareness of the role of immunotherapy in the treatment of diseases. Building on this, research scientists from the University of Oxford and the Ludwig Institute for Cancer Research are developing a new cancer vaccine that makes use of similar technology. The vaccine flags cancer-specific antigens to the immune system which causes an increase in the response of tumour-infiltrating T-cells.

In a study of mouse tumour models, the vaccine was shown to increase the levels of anti-tumour T-cells infiltrating the tumours, and as such, improved the efficacy of cancer immunotherapy. The cancer vaccine is now being assessed in a Phase 1/2a clinical trial featuring 80 patients with non-small cell lung cancer.

As Adrian Hill, Lakshmi Mittal and Family Professorship of Vaccinology and director of the Jenner Institute, University of Oxford puts it: “This new vaccine platform has the potential to revolutionise cancer treatment.”

Over the past decade, improved understanding of the immune system has inspired the pharmaceutical industry to explore its use in the treatment of cancer. Improved knowledge in these areas is helping drug companies to identify subsets of cancer patients who would benefit from specific cancer vaccines or other therapies. Improved detection of target biomarkers can also facilitate smaller, precision trials and shorten drug development timelines.

In particular, greater understanding of the human microbiome, particularly that of the gut, is helping drug developers to identify mechanisms of resistance and response to certain therapies. Using this knowledge, treatments can be directed to individuals who are pre-disposed to achievea better outcome. It is also hoped that better understanding of a patient’s microbiome could help to decrease the risk of toxic side effects and improve the efficacy of specific treatments.

Much innovation activity to date has centred on tumour-infiltrating lymphocytes (TILs) and CAR T-cell therapies - such as those targeting the antigens CD19, and more recently, BCMA. Some treatments focus on activating TILs, whilst others work by isolating and proliferating TILs from solid tumours to boost the quantity of tumour-reactive T-cells. CAR T-cell therapy is a type of immunotherapy involving the adoptive transfer of T-cells that have been genetically modified with a chimeric antigen receptor to target a tumour. CAR T-cell therapies have been found to be most effective in the treatment of blood cancers; however, considerable research activity is directed towards their utilisation and optimisation for solid tumour cancers.

Another important area of R&D is focused on immune checkpoint inhibitors (ICIs), which have shown great promise in improving the survival rates of some cancer patients. These treatments have been found to be particularly effective in the treatment of melanoma and non-small cell lung cancers. ICIs, such as anti-PD1, essentially work by releasing the brakes on T-cells to target and kill the cancer cells. However, the overall response rate of these therapies remains unsatisfactory and high-grade toxicity is a significant problem. For example, over 50% of those receiving anti-CTLA4 and anti-PD1 blockade may require hospitalisation.

To improve outcomes for cancer patients, some innovators are looking for ways to alter a patient’s gut microbiome in combination with immunotherapy. The gut’s microbiome comprises around 100 trillion micro-organisms, encoding over three million genes and producing thousands of metabolites. Convincing evidence is now emerging, suggesting that the gut microbiome could impact the development of some types of cancer – mainly those relating to the gastrointestinal and hepatobiliary systems. It could also impact responses to other cancer therapeutics such asICIs.

Research focuses on various ways of leveraging the microbiome such as microbial consortia or genetically modified microbial strains. Live biotherapeutics for use in the treatment of cancer may also prove particularly beneficial in improving outcomes when used as an adjuvant for treatments such as ICIs. For example, UK-based 4D Pharma PLC have an expanding portfolio of over 1,000 patents in the microbiome sector and their current pipeline focuses on the efficacy of lead products and candidates as monotherapies and combination treatments for cancer.

With drug companies learning more about how the gut microbiome can impact the outcome of patients receiving immunotherapy for the treatment of cancer, this strand of research and development is expected to continue to develop. With commercial protection in place, those responsible for discovering new ways to improve the efficacy of immuno-oncology treatments have an opportunity to leverage their innovations commercially, while improving outcomes for cancer patients the world over.