Vaccination with autologous tumour antigen-pulsed dendritic cells in advanced gynaecological malignancies: clinical and immunological evaluation of a phase I trial.
Dendritic cell (DC)-based therapy has proven to be effective in patients with malignant lymphoma, melanoma, and renal and prostate carcinoma. In this phase I clinical trial, we have shown that patients with advanced gynaecological malignancies can be effectively vaccinated with DC pulsed with keyhole limpet haemocyanin (KLH) and autologous tumour antigens. Two patients with uterine sarcoma and six subjects with ovarian carcinoma received three to 23 intracutaneous injections of antigen-pulsed DC at 10-day or 4-week intervals. Three patients showed stable disease lasting 25 to 45 weeks, and five experienced tumour progression within the first 14 weeks. KLH- and tumour lysate-specific delayed-type hypersensitivity (DTH) reactions were observed in six and one patient, respectively. Lymphoproliferative responses to KLH and to tumour lysate stimulation were recorded in six patients and in two patients respectively. Tumour antigen-stimulated interferon-gamma (IFN-gamma) secretion by peripheral blood mononuclear cells (PBMC) in one patient was consistent with a T(H) type 1 cytokine bias. The treatment was safe, well tolerated, immunologically active and except for local cutaneous hypersensitivity devoid of significant adverse effects.
Hernando
Juan José
JJ
Department of Obstetrics and Gynaecology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. j.hernando@uni-bonn.de
Park
Tjoung-Won
TW
Kübler
Kirsten
K
Offergeld
Ruth
R
Schlebusch
Harald
H
Bauknecht
Thomas
T
D000328:Adult; D017951:Antigen Presentation; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000276:immunology / Q000628:therapy*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007121:Immunocompetence; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D012509:Sarcoma / Q000276:immunology / Q000628:therapy*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000276:immunology / Q000628:therapy*; D014611:Vaccination
D019496:Cancer Vaccines; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin