CAR T cells - redirecting T cells for cancer immunotherapy

Chimeric Antigen Receptors (CARs) are genetically engineered molecules that can redirect T cells to recognise particular antigens, such as those expressed by cancer cells. T cells that are transduced by CAR targeting CD19 have been effective in treating B cell cancers, e.g. B-cell leukaemia and lymphoma, where conventional treatments have failed.

This exciting technology is one of the major breakthroughs in cancer therapy this decade. However, not all patients respond, not all responses are durable and there is limited success to date in CAR T cells targeting solid cancers.

This project involves developing and testing new concepts in CAR T cell engineering to make them more effective, safer and more able to target solid cancers. Our laboratory is involved in preclinical development, through to research translation and early phase clinical trials. There is also an opportunity for students to be involved in clinical correlative research to better understand the immunobiological determinants of clinical response and toxicity.

The overarching aim of this project is to develop safer and more effective CAR T cell therapies for blood cancers and solid cancers, and take these to early phase clinical trials. This is achieved through several interrelated projects with the following aims:

1. To investigate how CAR T cell function can be modulated by changing individual components within the CAR transgene.
2. To optimise methods for the clinical scale manufacture of CAR T cells as a precursor to future clinical trials
3. To examine the longitudinal fate of CAR T cells and the bystander immune compartment in patients undergoing CAR T cell therapy.

We use a range of immunology, molecular biology and cell therapy approaches to achieve these aims. Not all projects will involve all these approaches. Immunology techniques include cell culture, multiparametric flow cytometry (including spectral cytometry), live-cell imaging and a range of in vitro immunological assays (e.g. ELISA, cytokine bead array). Some projects will involve in vivo experiments using mouse models, and some projects will involve analysis of clinical samples. Molecular techniques include CAR gene design and cloning, and CRISPR/Cas9 gene knock-out. Cell therapy technology includes generation of viral vectors, small-to-large scale cell processing, including the the use of clean room suites within the Good Manufacturing Practice (GMP) facility.

The project is suitable for biomedical scientists and clinicians who are interested in wetlab research.

Students will have the opportunity to work on different phases of the development of a novel cell and gene therapeutic. All students will have the opportunity to work on the preclinical development and testing of novel CARs. Masters or PhD students may have the opportunity to work on clinical scale-up and technology transfer to Good Manufacturing Practice facility. PhD students may also have the opportunity to take a technology through to early phase clinical trial.