May 15, 2020

Developing “Off-the-Shelf” Therapies for People with Cancer

Helen Tayton-Martin

Cell therapies for cancer that use a patient’s own cells to fight disease are called autologous therapies, which have taken center stage in cancer research and treatment over the last few years. As a company, we have developed autologous T-cell therapies for many years, with promising results in synovial sarcoma. The efficacy we saw in sarcoma led us to start a Phase 2 clinical trial call SPEARHEAD-1, and we have also seen encouraging results in four additional solid tumors in other trials.

A few years ago, we began to expand our research into another type of cell therapy platform that does not require us to engineer a patient’s own T-cells. This platform is called allogeneic or “off-the-shelf”. Our work started based on a small team of about 5 people in 2015 working to make T-cells from edited stem cells in collaboration with a small gene editing company (Universal Cells) in Seattle. Today have more than 25 people working on the program and have made significant progress to make these off-the-shelf T-cells a reality. In theory, these allogeneic cell therapies can be administered to any eligible patient, as they are engineered through gene editing to be acceptable to any patient’s immune system. This universal approach would allow us to make such cell therapies much more mainstream and accessible to many more patients.  Our proprietary, stem-cell derived allogeneic technology is capable of producing functional T-cells and is applicable to a broad range of targets and modalities.

Recently, based on our industry leading stem-cell-based platform, one of the most advanced in the field, and our original collaboration with Universal Cells (now an Astellas Company), we signed a further strategic partnership with Astellas Pharma Inc in which we will co-develop and co-commercialise allogeneic therapies together, in addition to Adaptimmune’s own independent programs. Both companies believe this partnership will enable us to change the way we treat cancer patients.

Our expertise

One of the most exciting aspects of stem cell-derived allogeneic cell therapies is that it only requires one cell line for starting material. At Adaptimmune, we are using Human Induced Pluripotent Stem Cells (HiPSC). HiPSC have a high capacity for proliferation that could enable generation of large iPSC banks. These stem cells are also pluripotent, which means that they have the ability to generate any human cell type by a process known as differentiation. The purpose of our allogeneic program is to edit these stem cells with the right changes to prevent immune rejection whilst also including our engineered TCR genes to target different cancers.  These edited stem-cell lines are then differentiated into T-cells able to kill cancer cells. Through this process – we pick clones with the right characteristics and expand these into large cell banks that can then be held at the ready, in theory, for any eligible patient with cancer. 

We presented preliminary research from the program at the 2020 American Society of Gene & Cell Therapy Annual Meeting. Compelling data with our “off-the-shelf” SPEAR T-cell program showed that we are able to generate T-cells HiPSC in vitro and that these T-cells kill specific cancer targets after we engineer them to express one of our SPEAR T-cell Receptors (TCRs). You can watch a video of Jo Brewer, who leads our allogeneic team, talking about these data, and you can find the poster here

Expanding Our Resources Through Collaboration 

We are excited about the preliminary data we presented at ASGCT and believe our partnership with Astellas will also help to make our allogeneic T-cell research and development stronger through shared expertise. 

As part of our own allogeneic program, we have been using Astellas’ Universal Donor Cell and Gene Editing Platform obtained through its acquisition of Seattle-based Universal Cells. We had a long-standing collaboration with Universal Cells (since 2015) to develop gene-edited HiPSC cell lines, making this recent collaboration with Astellas a great fit for both companies.

The new collaboration will leverage our target identification and validation capabilities for generating T-cell receptors (TCRs) to target cancer for joint collaboration programs. The collaboration is not limited to TCRs, as we can also develop chimeric antigen receptors (CARs) to target cancer. In addition, we are working on HLA-independent TCRs (HiTs) that can recognize targets without the need for the usual antigen-presenting proteins called HLA, which could also be included in the collaboration. 

Another interesting feature of this collaboration is that it gives us the opportunity to co-develop and co-commercialize products. This is a very early-stage partnership for such an agreement, and we believe this demonstrates the commitment both companies have to broadening allogeneic therapies to cover a range of solid tumors and blood cancers.

Planning for the Future for Cell Therapies

Utilizing an allogeneic approach can address the two major manufacturing challenges current autologous therapies face: no starting inventory and variability of starting apheresis material. Firstly, since autologous therapies use a patient’s own cells, manufacturing cannot start until the cells are collected from the patient and delivered to the manufacturing site. The clock starts ticking as soon as the cells come out of the patient, so any last-minute changes to the collection or delivery process can greatly impact manufacturing planning.

Secondly, because these cells are taken from individual patients who have likely received multiple cancer treatments there is a lot of variation in the quality of cells. The starting material is different every single time since every patient is unique, making process validation and standardization difficult. 

When treatment can shift to allogeneic therapies, these challenges of autologous therapy would be overcome. Cells would be manufactured, frozen, and ready for use – and would be standardized. That is, patients would receive the same types of cells with known attributes without the dependence and variability of their own T-cells.

Eliminating the bespoke nature of harvest and manufacture of autologous cell therapies would allow patients to receive treatments with less variability than autologous therapies, more quickly, and in a more efficient way. This is crucial when treating late-stage metastatic cancers in patients who have few other treatment options. The sooner we can treat people with cancer, the more we increase the likelihood that the treatments will lead to better outcomes. We are excited to be a pioneer in this field developing “off-the-shelf” cell therapies and we look forward to working with Astellas along the way.