This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Loveland, B. E. Articles by Mitchell, P. L.R. Search for Related Content PubMed PubMed Citation Articles by Loveland, B. E. Articles by Mitchell, P. L.R.

Mannan-MUC1–Pulsed Dendritic Cell Immunotherapy: A Phase I Trial in Patients with Adenocarcinoma

Authors' Affiliation: Austin Research Institute, and Medical Oncology Unit, Austin Hospital, Heidelberg, Melbourne, Victoria, Australia

Requests for reprints: Bruce Loveland, The Austin Research Institute, Studley Road, Heidelberg, Victoria 3084, Australia. Phone: 61-3-9287-0666; Fax: 61-3-9287-0600; E-mail: b.loveland{at}ari.unimelb.edu.au.

Purpose: Tumor antigen-loaded dendritic cells show promise for cancer immunotherapy. This phase I study evaluated immunization with autologous dendritic cells pulsed with mannan-MUC1 fusion protein (MFP) to treat patients with advanced malignancy.

Experimental Design: Eligible patients had adenocarcinoma expressing MUC1, were of performance status 0 to 1, with no autoimmune disease. Patients underwent leukapheresis to generate dendritic cells by culture ex vivo with granulocyte macrophage colony-stimulating factor and interleukin 4 for 5 days. Dendritic cells were then pulsed overnight with MFP and harvested for reinjection. Patients underwent three cycles of leukapheresis and reinjection at monthly intervals. Patients with clinical benefit were able to continue with dendritic cell-MFP immunotherapy.

Results: Ten patients with a range of tumor types were enrolled, with median age of 60 years (range, 33-70 years); eight patients were of performance status 0 and two of performance status 1. Dendritic cell-MFP therapy led to strong T-cell IFN Elispot responses to the vaccine and delayed-type hypersensitivity responses at injection sites in nine patients who completed treatments. Immune responses were sustained at 1 year in monitored patients. Antibody responses were seen in three patients only and were of low titer. Side effects were grade 1 only. Two patients with clearly progressive disease (ovarian and renal carcinoma) at entry were stable after initial therapy and went on to further leukapheresis and dendritic cell-MFP immunotherapy. These two patients have now each completed over 3 years of treatment.

Conclusions: Immunization produced T-cell responses in all patients with evidence of tumor stabilization in 2 of the 10 advanced cancer patients treated. These data support further clinical evaluation of this dendritic cell-MFP immunotherapy.

This article has been cited by other articles:

				C. L-L. Chiang, J. A. Ledermann, E. Aitkens, E. Benjamin, D. R. Katz, and B. M. Chain Oxidation of Ovarian Epithelial Cancer Cells by Hypochlorous Acid Enhances Immunogenicity and Stimulates T Cells that Recognize Autologous Primary Tumor Clin. Cancer Res., August 1, 2008; 14(15): 4898 - 4907. [Abstract] [Full Text] [PDF]

				J. L. Gulley, P. M. Arlen, K.-Y. Tsang, J. Yokokawa, C. Palena, D. J. Poole, C. Remondo, V. Cereda, J. L. Jones, M. P. Pazdur, et al. Pilot Study of Vaccination with Recombinant CEA-MUC-1-TRICOM Poxviral-Based Vaccines in Patients with Metastatic Carcinoma Clin. Cancer Res., May 15, 2008; 14(10): 3060 - 3069. [Abstract] [Full Text] [PDF]