Pilot study of adoptive immunotherapy with sentinel node-derived T cells in muscle-invasive urinary bladder cancer

Abstract

Objective: The aim of this study was to determine by computed tomography (CT) whether treatment with tumor-draining lymph-node-derived expanded autologous T lymphocytes results in objective responses and/or improved survival in patients with metastatic urinary bladder cancer (UBC) and to record the toxicity of the treatment. Materials and methods: Eighteen patients with metastatic UBC were prospectively selected from two centers. The preoperative staging was T2–T4bN1–2 and/or M0–M1 or MX. Tumor-draining lymph nodes were harvested at intended cystectomy for the extraction of T lymphocytes. This was followed by expansion of the T lymphocytes in a cell culture, and subsequent reinfusion of these autologous tumor-specific T lymphocytes. Responses to therapy were evaluated by CT scans according to Response Evaluation Criteria In Solid Tumors (RECIST) and clinical follow-up, according to the research protocol. Results: Nine out of 18 patients were treated. Treatment was feasible and safe. In two out of nine immunologically treated patients, objective responses were detected in terms of diminished or obliterated nodal metastases. When excluding three patients with disseminated osseous metastases plus one with a T4b tumor left in situ, a success rate of two out of six treated patients was seen. The two responders had survival times of 35 and 11 months, respectively. No toxicity was recorded. Conclusions: Infusion of expanded autologous tumor-specific T lymphocytes is feasible and safe, and objective responses according to RECIST were recorded. One objective responder to immunotherapy displayed notably long overall survival.

Keywords :

• Adoptive cellular immunotherapy
• sentinel lymph-node biopsy
• urinary bladder neoplasms

Acknowledgements

This paper was supported by the Swedish Cancer Foundation, the Wallenberg Foundation and Swedish Research Council funding for clinical research in medicine (ALF) in Västerbotten, VLL, Sweden, Lions Cancer Research Foundation, Umeå University and the Cancer Research Foundation in Norrland, Sweden. The authors acknowledge the valuable assistance and administrative support of research nurses Runa Sandelin and Inga Hellström at the Department of Urology, Karolinska University Hospital, Stockholm, Sweden. We also acknowledge the administrative support of Per Gustafsson, nurse at the Department of Clinical Sciences, Surgery and Urology, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. Finally, we also acknowledge Dr Torsten Lindeborg, Department of Surgery and Urology, Mälarsjukhuset, Eskilstuna, Sweden, for valuable moral support.

Declaration of interest

For the author Ola Winqvist, two patents have been submitted and accepted; Cancer immunotherapy (prevention of cancer recurrence) and Method for treating urinary bladder cancer. Both patents are owned by Sentoclone International, in which he has no shares, and from which he receives no consultancy fees or any economic support. Ola Winqvist was also cofounder of the start-up company Sentoclone AB, which is now liquidated. All other authors declare no conflicts of interest.