Open Access Study protocol

Re-directed T cells for the treatment of fibroblast activation protein (FAP)-positive malignant pleural mesothelioma (FAPME-1)

Ulf Petrausch1*, Petra C Schuberth2, Christian Hagedorn2, Alex Soltermann3, Sandra Tomaszek4, Rolf Stahel2, Walter Weder4 and Christoph Renner12

Author affiliations

1 Department of Immunology, University Hospital Zurich, Rämistr. 100, 8091, Zürich, Switzerland

2 Department of Oncology, University Hospital Zurich, Rämistr. 100, 8091, Zürich, Switzerland

3 Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstr. 12, 8091, Zurich, Switzerland

4 Division of Thoracic Surgery, University Hospital Zurich, Rämistr. 100, 8091, Zurich, Switzerland

For all author emails, please log on.

Citation and License

BMC Cancer 2012, 12:615  doi:10.1186/1471-2407-12-615

Published: 22 December 2012

Abstract

Background

Asbestos is the main cause of MPM in industrialized countries. Even since asbestos is banned in most developed countries, the peak wave of MPM incidence is anticipated for the next years due to the long latency of asbestos induced MPM. MPM patients not eligible for surgical procedures like decortication or pleuro-pneumectomie have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation.

Methods/design

This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x106 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor recognizing FAP which serves as target structure in MPM. At day 0 of the protocol, re-directed T cells will be injected in the pleural effusion and patients will be monitored for 48h under intermediate care conditions. AE, SAE, SADR and SUSAR will be monitored for 35 days and evaluated by an independent safety board to define any dose limiting toxicity (DLT). No further patient can be treated before the previous patient passed day 14 after T cell transfer. The protocol will be judged as save when no DLT occurred in the first 3 patients, or 1 DLT in 6 patients. Secondary objectives are feasibility and immune monitoring.

Discussion

Adoptive T cell transfer is a new and rapidly expanding branch of immunotherapies focusing on cancer treatment. Recently, objective responses could be observed in patients with chronic lymphatic leukemia treated with adoptively transferred CD19-specific re-directed T cells. The choice of the target antigen determines the possible on-target off-tissue toxicity of such approaches. There are reports of severe toxicity in patients who received T cells intravenously due to unexpected expression of the target antigen (on-target) in other tissues than the tumor (off-tissue). To minimize the risk of on-target off-tissue toxicity and to maximize the on-target anti-tumor effect we propose a clinical protocol with loco-regional administration of re-directed T cells. FAP-specific T cells will be directly injected in the pleural effusion of patients with MPM.

Trial registration

ClinicalTrials.gov (NCT01722149)