Immunotherapy at UCL/UCLH Karl Peggs Professor of Transplant - PowerPoint PPT Presentation

Immunotherapy at UCL/UCLH Karl Peggs Professor of Transplant Science and Cancer Immunotherapy Scientific Director NIHR BTRU for Stem Cell Transplantation and Immunotherapy

An introduction to the immune system The opposite isn’t so great either This is your immune system. If the immune system is too weak, your body becomes It is vigilant on one end of a susceptible to infection. very complex balance. On the other end is your body, suspended over a sea of bacteria and viruses. The same is true of cancer, which suppresses immunity via a number of mechanisms. Immunotherapy aims to strengthen the ability of the immune system to fight cancer.

Mast cell B cell Macrophage Antibodies γδ T cell Basophil NK cell DCs T cell Eosinophil Complement protein NKT cell Neutrophil Granulocytes CD4 + cell CD8 + cell Innate Immunity Adaptive Immunity (rapid response) (slow response, memory) Innate immune system: involves proteins (chemokines and cytokines) and cells, is considered to be the first line of immune defense Adaptive immune system: mediated by B and T cells, is highly specific and capable of generating an antigen-specific response – Induction requires presentation of antigens by cells of the innate immune system

Antibodies as immunotherapies – original thinking

Antibodies – payload delivery 1 1 5 5 2 4 2 4 3 3 1 Antibody targets cell surface protein 2 Binding and internalization MMAE release: after internalization MMAE is released into the target cells 3 Microtubule disruption: binding of MMAE disrupts the microtubule network 4 Cell death: if microtubule disruption occurs, apoptotic cell death results 5

Antibodies - Immune Checkpoints APC/ T cell Tumour B7-2 (CD86) CD28 Activation B7-1 (CD80) CTLA-4 Inhibition PD-L1 PD-1 Inhibition Blocking antibodies targeting co-inhibitory receptors PD-L2 B7-1 (CD80) Inhibition LAG-3 Inhibition MHC TCR CD40 CD40L Activation Agonistic antibodies targeting co- CD137L CD137 Activation stimulatory receptors OX40L OX40 Activation

T cells and Tumour Control

T cells for relapsed disease after BMT Jan 03 - Aug 04 Nov 06 - Feb 08

Chimeric antigen receptors (CARs) CD19 CAR T cell trials: • COBALT: 2 nd generation CAR, bridge to allograft in DLBCL • D-CAR19: 2 nd generation CAR, for cancers relapsing post allograft • UniCAR19: 2 nd generation CAR, off the shelf third party treatment … paediatric ALL (CARPALL), adult ALL (i4i)

Delivery – a meeting of the minds U C L C A N C E R I N S T I T U T E

UCLH – state of the art immunotherapy service

UCL/UCLH – delivering the spectrum of cancer immunotherapy