Lucas Chan

Translational development and application of cell and gene therapy as Advanced Medicinal Products. In Acute Myeloid Leukaemia (AML), our current focus is in Immune Gene Therapy for AML, where we are conducting a clinical trial of an AML Cell Vaccine (ACV) by transducing patient derived leukaemia cells with an attenuated lentiviral vector expressing immune modulators CD80 and IL-2. The two Phase I clinical studies will evaluate any vaccine associated toxicity and potential immunological responses in both post-transplant relapsed AML patients and those ineligible to receive transplant.

Manufacturing of viral gene therapy and cell therapy products for other clinical studies both in house and for collaborative partners in academia and in industry.

List of cell and viral based therapies produced under Good Manufacturing Practice (GMP):

• DCVax – A Dendritic Cell based vaccine pulsed with tumour lysates for Glioblastoma Multiforme (Q3 2013) (Specials / Phase III) – In partnership with Northwest Biotherapeutics Inc. DCVax is the first Cell Therapy for cancer that has entered Phase III clinical trial.

• Enriched haplo-identical donor derived Natural Killer cells for adoptive transfer in relapsed Acute Myeloid Leukaemia (Pilot /Specials) – This was an in-house established protocol for the enrichment of NK cells by CD3/CD56 deplete/select strategy used in a pilot study. Enrichment results in >98% purity of NK cells.

• A retrovirus vector encoding a T cell receptor targeting Hepatitis B virus infected cells for immune gene therapy of HBV associated Hepatocellular Carcinoma (Pilot/Specials) – A multi- center pilot study in the first in man use of HLA-restricted hepatitis surface antigen targeted gene modified autologous T cells.

• A retrovirus vector encoding HSV-tk for the control of graft-versus-host disease following Adoptive transfer in Leukaemia (Phase I) – In collaboration with Great Ormond Street Children’s Hospital (GOSH).

• A self-inactivating lentivirus vector encoding CD80 and IL-2 (Phase I) – The first such GMP grade lentiviral vector manufactured approved by UK MHRA for clinical use.

• A lentivirus encoding SPINK5 for the treatment of Netherton syndrome (Phase I) – An active MHRA approved Phase I gene therapy study in collaboration with GOSH.

• A 293T based Master Cell Bank for the production of viral vectors for gene therapy – One of few comprehensively characterized 293T based MCB available.

Other ATMPs currently in early phase development:

• A lentiviral vector expressing anti-CD19 chimeric antigen receptor (CAR) for the modification of immune effector cells against lymphoblastic leukaemia.

• A lentiviral vector expressing Col7 for the modification of keratinocytes for the treatment of autoimmune skin disorders.

• A lentiviral vector expressing a CAR for the treatment of hepatocellular carcinoma.

Media

• A vaccine for leukaemia. Front page Article. The Telegraph. 4 January 2010.

http://www.telegraph.co.uk/health/healthnews/6872451/Leukaemia-vaccine-being-developed.html

• Leukaemia vaccine. NHS information service. Jan 2010.

http://www.nhs.uk/news/2010/01January/Pages/Leukaemia-vaccine-to-be-tested.aspx

• Revolutionary cancer treatment: Brain tumour cells to be used in personalised vaccines for injection into patients. The Mirror. 13 June 2012

http://www.mirror.co.uk/news/uk-news/brain-tumour-cells-to-be-used-in-personalised-880443

• Brain cancer vaccine trial. King’s College London News Brief. 14 May 2012

http://www.kcl.ac.uk/newsevents/news/newsrecords/2012/05May/Brain-Cancer-Vaccine.aspx