Original Article: Clinical Investigation
Immunotherapy against metastatic renal cell carcinoma with mature dendritic cells
Akihiko Matsumoto,
Kyoko Haraguchi,
Tsuyoshi Takahashi, Takeshi Azuma, Yoshinobu Kanda, Kyoichi Tomita, Mineo Kurokawa, Seishi Ogawa,
Koki Takahashi,
Shigeru Chiba,
Tadaichi Kitamura,
Akihiko Matsumoto
Departments of Urology,
Cell Therapy and Transplantation,
Search for more papers by this authorKyoko Haraguchi
Cell Therapy and Transplantation,
Hematology/Oncology,
Search for more papers by this authorSeishi Ogawa
Hematology/Oncology,
Regeneration Medicine for Hematopoiesis and
Search for more papers by this authorKoki Takahashi
Transfusion Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Search for more papers by this authorShigeru Chiba
Cell Therapy and Transplantation,
Hematology/Oncology,
Search for more papers by this authorCorresponding Author
Tadaichi Kitamura
Departments of Urology,
Tadaichi Kitamura md phd, Department of Urology, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo 113-8655, Japan. Email: [email protected]Search for more papers by this authorAkihiko Matsumoto,
Kyoko Haraguchi,
Tsuyoshi Takahashi, Takeshi Azuma, Yoshinobu Kanda, Kyoichi Tomita, Mineo Kurokawa, Seishi Ogawa,
Koki Takahashi,
Shigeru Chiba,
Tadaichi Kitamura,
Akihiko Matsumoto
Departments of Urology,
Cell Therapy and Transplantation,
Search for more papers by this authorKyoko Haraguchi
Cell Therapy and Transplantation,
Hematology/Oncology,
Search for more papers by this authorSeishi Ogawa
Hematology/Oncology,
Regeneration Medicine for Hematopoiesis and
Search for more papers by this authorKoki Takahashi
Transfusion Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Search for more papers by this authorShigeru Chiba
Cell Therapy and Transplantation,
Hematology/Oncology,
Search for more papers by this authorCorresponding Author
Tadaichi Kitamura
Departments of Urology,
Tadaichi Kitamura md phd, Department of Urology, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo 113-8655, Japan. Email: [email protected]Search for more papers by this authorAbstract
Objective: We performed a clinical trial of immunotherapy using autologous mature dendritic cells (DC) pulsed with autologous tumor lysate, for patients with metastatic renal cell carcinoma (RCC).
Methods: Patients with refractory metastatic RCC were enrolled in the study. All of them received interferon (IFN)-α treatment after nephrectomy and were followed over 3 months prior to this study. Autologous monocyte-derived immature DC were pulsed with lysate from autologous primary tumor as the antigen and keyhole limpet hemocyanin (KLH) as immunomodulator, and cultured in the presence of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and prostaglandin (PG)E2 to generate mature DC. Mature DC were injected intradermally near bilateral inguinal lymph nodes of the patients. A delayed-type hypersensitivity (DTH) test and enzyme-linked immunospot (ELISPOT) assay were performed to evaluate the immunological response. After 4 months from first injection, the clinical effect was evaluated by diagnostic imaging.
Results: The treatments were well tolerated without significant toxicity by the patients who were an average of 65.7 years old and had multiple metastases in the lung and other organs. One of the two patients developed a positive DTH reaction to tumor lysate and the other patient only to KLH. The patient with a positive DTH reaction to tumor lysate had stable disease in the clinical evaluation.
Conclusions: We confirmed the safety of DC therapy in this clinical trial. The DTH test revealed that the DC therapy induced immunological response to RCC. On the other hand, it was necessary to reconsider the patient selection criteria.
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