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- Title
Phase I Study of Autologous Tumor Vaccines Transduced with the GM-CSF Gene in Four Patients with Stage IV Renal Cell Cancer in Japan: Clinical and Immunological Findings
- Authors
Tani, Kenzaburo; Azuma, Miyuki; Nakazaki, Yukoh; Oyaizu, Naoki; Hase, Hidenori; Ohata, Junko; Takahashi, Keisuke; OiwaMonna, Maki; Hanazawa, Kisaburo; Wakumoto, Yoshiaki; Kawai, Kouji; Noguchi, Masayuki; Soda, Yasushi; Kunisaki, Reiko; Watari, Kiyoshi; Takahashi, Satoshi; Machida, Utako; Satoh, Noriharu; Tojo, Arinobu; Maekawa, Taira
- Abstract
We produced lethally irradiated retrovirally GM-CSF-transduced autologous renal tumor cell vaccines (GVAX) from six Japanese patients with stage IV renal cell cancer (RCC). Four patients received GVAX ranging from 1.4 × 108 to 3.7 × 108 cells on 6–17 occasions. Throughout a total of 48 vaccinations, there were no severe adverse events. After vaccination, DTH skin tests became positive to autologous RCC (auto-RCC) in all patients. The vaccination sites showed significant infiltration by CD4+ T cells, eosinophils, and HLA-DR-positive cells. The kinetic analyses of cellular immune responses using peripheral blood lymphocytes revealed an enhanced proliferative response against auto-RCC in four patients, and cytotoxicity against auto-RCC was augmented in three patients. T cell receptor β-chain analysis revealed oligoclonal expansion of T cells in the peripheral blood, skin biopsy specimens from DTH sites, and tumors. Western blot analysis demonstrated the induction of a humoral immune response against auto-RCC. Two of the four patients are currently alive 58 and 40 months after the initial vaccination with low-dose interleukin-2. Our results suggest that GVAX substantially enhanced the antitumor cellular and humoral immune responses, which might have contributed to the relatively long survival times of our patients in the present study.
- Subjects
CANCER treatment; VACCINATION; IMMUNIZATION; LYMPHOCYTES
- Publication
Molecular Therapy, 2004, Vol 10, Issue 4, p799
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2004.07.001