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Phase II trial of B7-1 (CD-86) transduced, cultured autologous tumor cell vaccine plus subcutaneous interleukin-2 for treatment of stage IV renal cell carcinoma.
- Source :
-
Journal of immunotherapy (Hagerstown, Md. : 1997) [J Immunother] 2008 Jan; Vol. 31 (1), pp. 72-80. - Publication Year :
- 2008
-
Abstract
- We report a single center phase II trial of sequential vaccination followed with vaccine plus interleukin-2 (IL-2). Vaccination consisted of autologous cells cultured from primary tumor or resected metastasis, transduced to express B7.1 surface molecule and then irradiated. The vaccine would hypothetically costimulate tumor-reactive T cells before IL-2 exposure. Treatment plan was 3 subcutaneous vaccine injections at 4-week intervals and subcutaneous IL-2 treatment for 6 weeks starting at week 7. Sixty-six patients enrolled, of whom 39 received at least 1 vaccine; most observed toxicity was attributable to IL-2 not vaccine; best responses were 3% pathologic complete response, 5% partial response, 64% stable disease, and 28% disease progression. Median survival was 21.8 months (95% confidence interval 17.8 to 29.6). Significant postvaccination increases in IFN-gamma responses to autologous tumor were observed in 2/26 cases. Eighty-one percent of posttreatment subdermal delayed-type hypersensitivity tests (using nontransduced, irradiated autologous tumor cells) had biopsies demonstrating injection site lymphocytic infiltration. Post hoc comparison of the median survival of subjects whose biopsies had lymphocytic infiltration appears longer than in the 19% noninfiltrated (28.4 vs. 17.8 mo, P=0.045, two-sided log-rank test). The single arm design precludes conclusive comparison of objective response rates (not different here) or median survival (longer here) versus those of historical series using similar IL-2 schedules alone. Better outcomes could be logically associated to vaccine response (detectable lymphocytic infiltrates) or to random events that a single arm study design cannot address. This vaccine approach may merit further clinical development.
- Subjects :
- Adult
Aged
Aged, 80 and over
B7-1 Antigen genetics
Cancer Vaccines adverse effects
Cancer Vaccines immunology
Carcinoma, Renal Cell immunology
Carcinoma, Renal Cell pathology
Female
Humans
Interferon-gamma metabolism
Interleukin-2 adverse effects
Kidney Neoplasms immunology
Kidney Neoplasms pathology
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear immunology
Leukocytes, Mononuclear metabolism
Liver drug effects
Liver immunology
Liver pathology
Male
Middle Aged
Neoplasm Staging
Skin drug effects
Skin immunology
Skin pathology
Survival Analysis
Transfection
Treatment Outcome
Tumor Cells, Cultured
B7-1 Antigen immunology
Cancer Vaccines therapeutic use
Carcinoma, Renal Cell therapy
Interleukin-2 therapeutic use
Kidney Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1524-9557
- Volume :
- 31
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunotherapy (Hagerstown, Md. : 1997)
- Publication Type :
- Academic Journal
- Accession number :
- 18157014
- Full Text :
- https://doi.org/10.1097/CJI.0b013e31815ba792