Amir Sherif1, Mudhar N Hasan2, Eva Radecka3, Alvaro Lozano Rodriguez4, Sarab Shabo5, Mona Karlsson6, Martin C Schumacher7, Per Marits6, Ola Winqvist6. 1. a 1 Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University , Umeå, Sweden. 2. b 2 Department of Clinical Sciences, Surgery and Urology, Danderyd Hospital, Karolinska Institutet , Sweden. 3. c 3 Department of Diagnostic Radiology, Karolinska University Hospital, Karolinska Institutet , Stockholm, Sweden. 4. d 4 Servicio de Radiología, Hospital Universitario Insular de Gran Canaria , Las Palmas, Spain. 5. e 5 Department of Surgery and Urology, Mälarsjukhuset , Eskilstuna, Sweden. 6. f 6 Translational Immunology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet , Stockholm, Sweden. 7. g 7 Department of Urology, Hirslanden Klinik , Aarau, Switzerland.
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.
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.
Authors: Robert Rosenblatt; Markus Johansson; Farhood Alamdari; Alexander Sidiki; Benny Holmström; Johan Hansson; Janos Vasko; Per Marits; Susanne Gabrielsson; Katrine Riklund; Ola Winqvist; Amir Sherif Journal: World J Urol Date: 2016-10-13 Impact factor: 4.226