Principal Investigator Akseli Hemminki

Principal Investigator:

Professor Akseli Hemminki, MD, PhD

Primary Affiliation:

University of Helsinki and Helsinki University Central Hospital, Cancer Gene Therapy Group

Title of the FIMM-Specific Research Project:

Translational cancer gene therapy for induction of antitumor immunity

Abstract:

Accumulating evidence indicates that a dynamic cross-talk between tumors and the immune system can regulate tumor growth and metastasis. In this context, a promising approach for improving therapeutic options for tumors currently incurable involves potentiation or redirection of the tumor immune response. The combination of oncolytic adenoviruses and immunotherapy has not been explored yet in detail. Different strategies can be used to enhance the T cell response towards the tumor: A) Recruiting Dendritic Cells (DCs) to the tumor site to augment peptide loading onto MHC I; B) specifically activate DCs at the tumor site to increase their expression of co-stimulatory molecules enhancing cross-priming and T cell activation rather than cross-tolerance. In this FIMM specific project we will combine both of these aspects together with effective oncolytic cancer cell killing targeted to tumor cells. These goals will be realized by construction and preclinical testing of Ad5/3-D24-CpG-GM-CSF. The virus is targeted to the tumor selective adenovirus 3 receptor. Replication and oncolysis are restricted to tumor cells through the D24 deletion which allows virus activation selectively in p16/Rb pathway defective cells. DC recruitment is mediated by GMCSF expression and DCs are stimulated with the CpG moieties incorporated in the genome of the virus.

This approach is a new concept in cancer gene therapy and it will give the field new insight into understanding the complexity of advanced tumors and their immunobiology.

Contact information:

Akseli Hemminki, MD, PhD

K. Albin Johansson Research Professor (Finnish Cancer Institute)

Cancer Gene Therapy Group

Molecular Cancer Biology Program & Transplantation Laboratory & Haartman
Institute

University of Helsinki and Helsinki University Central Hospital

Biomedicum B506b, P.O.Box 63 (Haartmaninkatu 8)

FI-00014 University of Helsinki, Finland

Tel: +358-9-1912 5464

Fax: +358-9-1912 5465

e-mail: akseli.hemminki(at)helsinki.fi

home page: http://www.hi.helsinki.fi/cgtg