Immunotherapy against metastatic renal cell carcinoma with mature dendritic cells.
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)-alpha 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)-alpha, interleukin (IL)-1beta, 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.
Matsumoto
Akihiko
A
Department of Urology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Haraguchi
Kyoko
K
Takahashi
Tsuyoshi
T
Azuma
Takeshi
T
Kanda
Yoshinobu
Y
Tomita
Kyoichi
K
Kurokawa
Mineo
M
Ogawa
Seishi
S
Takahashi
Koki
K
Chiba
Shigeru
S
Kitamura
Tadaichi
T
D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000556:secondary / Q000628:therapy*; D003713:Dendritic Cells; D006801:Humans; D016233:Immunotherapy, Active; D007680:Kidney Neoplasms / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000556:secondary / Q000628:therapy*; D016896:Treatment Outcome
D019496:Cancer Vaccines