title: 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.
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.
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Mayer
authors.initials: M
authors.lastname: Fishman
authors.forename: Terri B
authors.initials: TB
authors.lastname: Hunter
authors.forename: Hatem
authors.initials: H
authors.lastname: Soliman
authors.forename: Patricia
authors.initials: P
authors.lastname: Thompson
authors.forename: Mary
authors.initials: M
authors.lastname: Dunn
authors.forename: Renee
authors.initials: R
authors.lastname: Smilee
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Farmelo
authors.forename: David R
authors.initials: DR
authors.lastname: Noyes
authors.forename: John J
authors.initials: JJ
authors.lastname: Mahany
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Alan
authors.initials: A
authors.lastname: Cantor
authors.forename: Jane
authors.initials: J
authors.lastname: Messina
authors.forename: John
authors.initials: J
authors.lastname: Seigne
authors.forename: Julio
authors.initials: J
authors.lastname: Pow-Sang
authors.forename: William
authors.initials: W
authors.lastname: Janssen
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Antonia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016019:Survival Analysis; D014162:Transfection; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D018122:B7-1 Antigen; D019496:Cancer Vaccines; D007376:Interleukin-2; D007371:Interferon-gamma