Oxford BioMedica
Discover Realise

CAR-T cell therapy

The Group is developing a product which combines both its LentiVector® and 5T4 technology platforms. The product is based on a gene modified autologous T-cell which is engineered using a lentiviral vector to express an antibody against 5T4. The T-cell is then infused into the patient where it recognises the 5T4 tumour antigen and triggers the “normal” T-cell killing mechanisms which kills the cancer cell. This innovative approach directly primes the immune system against the 5T4 antigen, by presenting the antigen on T-cells which are responsible for detecting foreign antigens. This new product is currently in pre-clinical stage development.

Cell therapy applications for gene therapy
Cell therapy usually involves the modification of cells in some way. These cells are then used as therapeutic agents to treat or prevent disease through their introduction back into the body. One of the main ways to modify the cells is through gene therapy and a successful cell therapy approach at present is the use of CAR-T as explained below.

CAR-T technology explained
Chimeric antigen receptors (CARs), also known as artificial T-cell receptors are genetically engineered receptors which graft a new specificity onto an immune effector cell. Typically, these receptors are used to graft the specificity of a monoclonal antibody onto a T-cell; normally carried out by a lentiviral vector. CAR T-cells are under investigation as a therapy for cancer, using a technique called adoptive cell transfer in which T-cells are removed from a patient and modified so that they express receptors specific to the particular form of cancer. The T-cells are reintroduced into the patient with the ability to recognise and kill the targeted cancer cells. In addition, these CAR T-cells proliferate, thus amplifying the beneficial response. This is a very powerful therapy and has led to dramatic response rates.

CAR T-cell therapy for cancer
01. OXB Solutions produces GMP lentiviral vector encoding CAR targeting CD19 which is expressed on B-cell lymphomas

02. T-cells isolated from patients

03. Lentiviral vector encoding CAR targeting CD19 used to transduce expanded T-cells. T-cells harvested from a patient are transduced with the lentiviral vector encoding the anti-CD19 chimeric antigen receptor. The resulting CTL019 cells are expanded ex vivo prior to infusion into the patient

04. The modified T-cells are infused back into the patient

05. Once inside the patient, the CTL019 cells multiply, ‘hunt’ cancer cells and destroy them. The CTL019 cells destroy tumour cells expressing CD19 and persist in the body to guard against residual or recurring disease

OXB-302, the 5T4 targeting CAR-T (Chimeric Antigen Receptor modified T cell), is currently in research/pre-clinical development and preliminary results have demonstrated proof of concept in an industry standard model. Pre-clinical development is expected to complete during 2016.