Betting big on Gamma Delta T Cells
News 7th Aug 2017

Betting big on Gamma Delta T Cells

Gamma Delta T Cells live in our tissue and form a crucial part of our immune system. Until recently, they have been on the sidelines of cancer research, but a $100m cash injection from drug giant Takeda Pharmaceuticals into a small biotech firm with big ideas in this area is set to change that, bringing a new class of immunotherapies one step closer to reality.


Gamma Delta T Cells live in our tissue and form a crucial part of our immune system. Until recently, they have been on the sidelines of cancer research, but a $100m cash injection from drug giant Takeda Pharmaceuticals into a small biotech firm with big ideas in this area is set to change that, bringing a new class of immunotherapies one step closer to reality.

Gamma Delta T Cells are either tissue or blood-derived. They have been of interest to the scientific community for many years, with advancements in knowledge in the last 15-20 years generating important steps forward in the field. For example, research in mice has shown that defects in these cells result in a significant increase in tumour occurrence and severity, while studies conducted in large samples of tumours in humans have revealed that the presence of Gamma Delta T Cells is a major positive prognostic factor for overall survival across 39 tumour types.


Digging deeper

Research into new therapies for solid tumours has not traditionally focused on these unique lymphocytes. Firstly, the mechanisms behind their striking activity on tumour cells in vitro have not been well understood. Secondly, it has not been possible to obtain enough of them to study or use an effective treatment, particularly in the case of tissue-derived cells.

However, Professor Adrian Hayday of King’s College London decided to delve a bit deeper. He discovered that tissue-resident Gamma Delta T Cells are distinct from their better known Alpha Beta counterparts in several key ways. While Alpha Beta T Cells need to be primed to recognise antigens before they can be recruited to sites of infection, Gamma Delta T Cells recognise patterns of dysregulation within the tissue itself and can then respond immediately, killing infected or transformed cells.


"The cells can then be reinjected back into the patient from which they were taken, killing cancer cells."


Based on this and other observations, Hayday and his colleague Dr Oliver Nussbaumer managed to develop a two-step platform that first isolates and extracts these cells from tissues, preserving their quality, quantity, and function, and amplifies and expands the population of the cells. The idea is that the resultant larger quantity of cells can then be reinjected back into the patient from which they were taken, killing cancer cells.

GammaDelta Therapeutics is a small biotech firm formed with the help of life science investment company Abingworth and Cancer Research UK to develop Hayday and Nussbaumer’s innovative platform. CEO Paolo Paoletti said: “We know that in vitro, tissue-resident Gamma Delta T Cells kill cancer cells once they have been isolated. We want to see if this will be replicated in humans.”


Full steam ahead

At present, the platform’s development is still in its very early stages. Thanks to a recent injection of $100m from drug giant Takeda Pharmaceuticals, which also holds on to the exclusive right to buy GammaDelta Therapeutics, it will now go full steam ahead.

Before becoming CEO of GammaDelta, Paoletti had a long run through the ranks of corporate pharmaceuticals, including heading up the oncology department at GSK. He says: “The ultimate goal of the company is to exploit our understanding of Gamma Delta T cells to develop effective therapeutics for patients suffering from cancer and auto-inflammatory diseases, so our main focus will be to optimise the process of isolating, amplifying and expanding these cells and then create an autologous cell therapy, whereby we will reinject the same cell taken from the same patient in larger quantities."

"The team will use the $100m investment to improve their understanding of the cells’ biology."

In addition, the team will use the $100m investment to improve their understanding of the cells’ biology. This also comes with an equity investment, an option fee, and research and development (R&D) funding. 

Paoletti notes: “This is a very young biology so by isolating these cells from normal tissue and from tissue with cancer, we should be able to understand better how we can enhance the activity of these cells and develop agents for the treatment of cancer and auto-inflammatory diseases."

One important characteristic of the cells is that they do not depend on the major histocompatibility complex (MHC). In other words, my Gamma Delta T-Cells can be given to you, and yours can be given to me.

Paoletti explains: “In theory they can be used off the shelf."

Unprecedented path

Looking ahead, Paoletti is keen to stress that the team is still at a very early stage of the development of their technologies, and challenges will include establishing a good manufacturing practice (GMP) compliant protocol for expansion of the cells for clinical applications and scaling up such processes for commercial products.

Paoletti says: “Being pioneers in the tissue-resident Gamma Delta T cell space means that we have fewer precedents to rely on and hence have to overcome each of the challenges ourselves. This is what makes our efforts greatly challenging and exciting in equal measure.

 “Our pre-clinical data shows that we can treat solid tumours, and this is something different to a lot of the cell therapy that is happening as we speak, which is mostly in leukaemia and lymphoma

“Takeda researchers were immediately able to understand the potential of our platform and as the chemistry was so good between Takeda and ourselves, we are excited to work together with them to give the best chance for this science to become a reality not only for cancer patients but also for patients with auto-inflammatory disease.”