Background for the press release,
January 22, 2009 :
"12,5 millioner kr. til banebrydende kræftforskning"

Grant support to a international collaborative effort initiated by CCIT

The Strategic Research Council Program, Committee for Research in Health, Food, and Biological Manufacturing have supported Per thor Straten, Director at Center for Cancer Immune Terapi, Department of Hematology, University Hospital Herlev with a grant of 12.664.500 DKK. The project, which has a duration of five years, is entitled "Development and clinical evaluation of new strategies for adoptive cell transfer (ACT) in the treatment of cancer", is carried out in collaboration with scientists from Holland, Norway, England and Denmark and has a compiled budget of more than 28.000.000 DKK.

Adoptive cell transfer (ACT) of in vitro expanded autologous tumor infiltrating lymphocytes (TIL) has been shown to possess therapeutic efficacy in melanoma patients. In the present project this treatment will be established for patients with melanoma and head and neck squamous cell carcinoma (HNSCC). However, in approx. 50 % of the patients with melanoma and HNSCC, it is not possible to expand TIL in vitro. To allow the extension of ACT to this patient group, these patients will be offered a therapeutic anti-cancer vaccination with the aim of inducing tumor specific T cells in the blood of the patient. Such cells are subsequently harvested by leukapheresis, expanded in vitro and used for ACT. In these trials, an extensive study of transferred T cells will be performed to enhance our understanding of T cell/cancer cell interactions in a clinically relevant setting i.e., in patients responding to treatment.

T cells recognize antigen on tumor cells by means of the clonally expressed T cell receptor (TCR). With the aim to transform ACT into a broadly applicable clinical strategy, T cells from patients that respond clinically to treatment will be isolated for cloning of a panel of TCRs for subsequent transfection of peripheral blood T cells. This approach of TCR gene transfer will be used to endow autologous T cells with tumor specificity. Within the current project T cells generated by such TCR gene transfer will be extensively studied, in preparation for subsequent clinical evaluation of use of TCR modified T cells in ACT. Such an off-the-shelf strategy cell transfer can be conducted repeatedly with a range of TCR specificities that match the individual patient.

In addition, we will modify wild type TCRs for improved affinity, and these will represent the next generation TCRs for transfection and clinical application after careful examination for specificity and function 6.

Thus the main objectives in the project are:

1. To establish adoptive cell therapy (ACT) for the treatment of cancer patients (HNSCC and melanoma) using expansion of TIL, and transfer back to the patient after lymphodepleting conditioning.
2. Establisment of a more broadly applicable strategy for ACT therapies, by in vitro expansion of vaccination induced T cells, and ACT of these cells to the patient after conditioning.
3. Isolations of clinically relevant TCRs from responding patients. TCR's will be tested and optimized for use in future clinical trials. This sets the stage for establishment of "off the shelf" ACT, by transfection of such TCR to patient peripheral blood T cells, and transfer back to the patient after conditioning. This strategy will be tested in pre-clinical experiments, evaluating a range of parameters of the transfected cells.

In addition to CCIT, the project group comprise Prof. Ton Schumacher, Department of Immunology, Netherlands Cancer Institute, Amsterdam, Holland, Prof. Gustav Gaudernack. Section for Immunotherapy, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway, Prof. Niels Ødum Department of Biology, Division of Immunology, The Panum Institute, University of Copenhagen. Also, Adaptimmune Ltd which is located in Oxfordshire, UK is included as an enterprise partner.

The clinical part of the study is headed by Inge Marie Svane, Director at CCIT, whereas the experimental part is headed by Sine Hadrup, Junior Group leader at CCIT.

Per thor Straten, PhD
Director at CCIT

Contact information:

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Last update: January 22, 2009