Chimeric Antigen Receptor (CAR) T-cell therapies for haematological malignancy have revolutionised
the treatment of patients with relapsed/refractory B-cell cancers. The scope of these therapies in other
haematological and even solid cancers holds much promise for the future.
However, there are several major bottlenecks for delivery of these novel therapies: availability of
academic clinical trials for CAR T-cell therapies is limited in the UK and in particular, the paucity of
manufacturing slots means that the majority of potentially eligible patients cannot access these
therapies. Streamlining the manufacturing process and pipeline to enhance manufacturing capability
and scalability would begin to address this challenging issue. Secondly, a large proportion of patients
referred for consideration of autologous CAR T-cell therapy are heavily pre-treated with chemotherapy
and their T-cell populations for harvest are often numerically (and in some cases functionally)
compromised. Referring patients early, prior to several lines of toxic chemotherapy would be optimal,
but this is logistically challenging. Another approach would be to review apheresis practice and work
to enhance T-cell collection at the front end. Lastly, these new therapies are associated with a constellation of unique potential side effects. The
clinical delivery of bespoke gene-modified T-cell therapies in routine Haemato-Oncology Units
requires a paradigm shift in medical, nursing, pharmacy and stem cell lab care pathways. This project undertakes to address these issues through the initiation and delivery of an academic study
of autologous CD19 CAR T-cells for relapsed/refractory acute lymphoblastic leukaemia (B-ALL). This
project will (1) investigate and establish a streamlined manufacturing platform for CAR T-cell
manufacture for the UCL CAR T-cell programme; (2) explore the single-centre apheresis practice at
UCLH to define a model/guideline for successful CAR T-cell apheresis and (3) to begin to establish the
clinical infrastructure required to deliver these therapies ‘routinely’ at a large central London teaching
hospital.