Activation methods and their role in CAR T-cell therapy production

Industrial Design Student 2020

Roumyana Kotopanova
Royal College of Art / Service Design

Cell and gene therapies aim to treat previously incurable diseases, particularly rare diseases and various types of cancer, by establishing the normal function of genes, cells, and tissues. This is achieved by the restoration or alteration of particular sets of cells in vivo (inside of the body) or ex vivo (outside of the body) and injecting them into the patient or by replacing, inactivating, or introducing a gene into a patient’s cells.

A type of disease that traditional therapies have not been able to fully cure are various types of blood cancers. Acute lymphoblastic leukaemia is an example of a malignancy which is accountable for 75% of leukaemia cases in children. Radiotherapy and chemotherapy are the current first-line treatment, but they are associated with off-target toxicity and long duration, resulting in a significant reduction of patients’ quality of life. In addition, 10% of patients fail to achieve remission, which underlines the need for an alternative treatment.

This project is focussed on improving the production of CAR T-cell therapy, a genetically modified cell therapy used in patients with relapsed acute lymphoblastic leukaemia, B-cell lymphoma, and mantle cell lymphoma. CAR T incorporates the reprogramming of a patient’s own T-lymphocytes to express a chimeric antigen receptor (CAR) which binds to the CD19 antigen on cancer cells and kills them directly, and/or indirectly by activating other cells of the immune system. While the T-cells are engineered ex vivo, they are activated using different methods that mimic the natural activation of T-cells in the body, such as a type of beads with attached monoclonal antibodies. The cost of the materials in the activation step is very high, making it one of the main cost drivers in the CAR T production process. As a result, novel ways of T-cell activation are being explored in the current project to determine a more cost-effective stimulation strategy. The main aim is to reduce the selling price per dose of CAR T-cell therapy, thus, making it available to those who need it, potentially as a first-line treatment.

This presentation was recorded in conjunction with our 1851 Virtual Alumni Science Evening 2021