Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.
Bioactivity of a human GM-CSF tumor vaccine for the treatment of metastatic renal cell carcinoma (Meeting abstract).
Proc Annu Meet Am Soc Clin Oncol; 15:A585 1996. Unique Identifier : AIDSLINE ICDB/97635585 Jaffee EM; Marshall F; Weber C; Pardoll DM; Levitsky H; Nelson W; Carducci M; Mulligan R; Simons J; The Johns Hopkins School of Medicine, Baltimore, MD 21205
Abstract:
Tumor cells retrovirally transduced to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) induce potent T cell mediated immune responses that can cure mice of 4 pre-established tumor burdens. Based on these findings, a randomized, double-blinded, dose-escalating phase I trial was conducted to compare autologous, irradiated, untransduced tumor cells with autologous, irradiated, GM-CSF secreting tumor cells for safety and the induction of antitumor immunity. Patients were required to have an ECOG performance status of less than 2, biopsy proven stage 3b or 4 renal cell carcinoma, and to be seronegative for HIV. Between December, 1993 and June, 1995, 17 patients underwent nephrectomy and received a vaccine. Six patients received 4x10(6) vaccine cells (tier 1), 3 on each arm. Of 7 patients receiving 4x10(7) vaccine cells (tier 2), 3 received the GM CSF vaccine. Two patients received 4x10(8) unmodified vaccine cells (tier 3). Two patients received GM-CSF vaccine cells at suboptimal doses. All participants in both vaccine groups experienced grade local induration and erythema at the vaccine site. No dose-limiting toxicities were encountered in either group. There was no evidence of autoimmunity including nephritis with a follow-up of 8 months post-vaccination. Delayed type hypersensitivity responses (DTH) to both autologous tumor cells and autologous normal kidney cells were observed in all individuals in both vaccine groups on dose tiers 2 and 3. However, there was a 4 fold difference in magnitude of the maximal response measured for 2/3 patients receiving the GM-CSF vaccine as compared to patients receiving the unmodified cells. The largest measured DTH response occurred in a patient receiving the GM-CSF vaccine in whom a partial clinical response was measured. Immunohistochemical staining of skin biopsies from patients receiving the GM-CSF vaccine demonstrated eosinophil and macrophage infiltration at the vaccine sites, and eosinophils, lymphocytes, and macrophages at the DTH sites. Eosinophils were absent in biopsies from patients receiving the unmodified vaccine cells. No replication competent retrovirus was detected in patients receiving the GM-CSF vaccine. We conclude that autologous GM-CSF secreting tumor vaccines are safe and so can be administered as outpatient therapy. In addition, this vaccine induces a dose-dependent immunity as measured by DTH responses. These findings, together with an observed partial clinical response, provide strong support for accelerating the evaluation of GM-CSF vaccines in patients with minimal residual disease.
Keywords: *Cancer Vaccines Carcinoma, Renal Cell/IMMUNOLOGY/*THERAPY Eosinophils/IMMUNOLOGY Granulocyte-Macrophage Colony-Stimulating Factor/*ADMINISTRATION & DOSAGE/SECRETION Human Immunity, Cellular Kidney Neoplasms/IMMUNOLOGY/*THERAPY Lymphocytes/IMMUNOLOGY Macrophages/IMMUNOLOGY Neoplasm Metastasis ABSTRACT 970330
M9731537
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Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.
