Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100

Monica C. Panelli, John Wunderlich, Justin Jeffries, Ena Wang, Arnold Mixon, Steven A. Rosenberg, Francesco M. Marincola

Research output: Contribution to journalArticle

Abstract

Dendritic cells (DCs) have been shown to enhance anti-tumor immune responses in several preclinical models. Furthermore, DC-like function can be elicited from peripheral blood monocytes cultured in vitro with interleukin-4 and granulocyte-macrophage colony-stimulating factor. For this reason, a phase I study was initiated at the Surgery Branch of the National Cancer Institute to test the toxicity and biological activity of the intravenous administration of peripheral blood monocyte-derived DCs. The DCs were generated by 5- to 7-day incubation in interleukin-4 (1,000 U/mL) and granulocyte-macrophage colony-stimulating factor (1,000 U/mL) of peripheral blood monocytes obtained by leukapheresis. Before administration, the DCs were pulsed separately with the HLA-A*0201-associated melanoma epitopes MART-I27-35 and gp-100-209-2M. The DCs were administered four times at 3-week intervals. A first cohort of patients (n = 3) was treated with 6 x 107 DCs and a second cohort (n = 5) with 2 x 108 DCs (in either case, one half of the DCs were pulsed with MART-127-35 and the other half was pulsed with gp-100-209-2M). In a final cohort under accrual (n = 2) 2 x 108 DCs were administered in combination with interleukin-2 (720,000 IU/kg every 8 hours). The recovery of DCs after in vitro culture ranged from 3% to 35% (mean, 15%) of the original peripheral blood monocytes. Administration of DCs caused no symptoms at any of the doses, and the concomitant administration of interleukin-2 did not cause toxicity other than that expected for interleukin-2 alone. Monitoring of patients' cytotoxic T lymphocyte reactivity before and after treatment revealed enhancement of cytotoxic T lymphocyte reactivity only in one of five patients tested. Of seven patients evaluated for response, one had a transient partial response with regression of pulmonary and cutaneous metastases. A relatively large number of DCs can be safely administered intravenously. The poor clinical outcome of this study perhaps could be explained by the type of protocol used for DC maturation, the route of administration, or both. For this reason, this clinical protocol was interrupted prematurely, whereas other strategies for DC preparation and mute of administration are being investigated at the authors' institution.

Original languageEnglish (US)
Pages (from-to)487-498
Number of pages12
JournalJournal of Immunotherapy
Volume23
Issue number4
DOIs
StatePublished - Jul 2000
Externally publishedYes

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Melanoma-Specific Antigens
Dendritic Cells
Epitopes
Melanoma
Immunization
Monocytes
Interleukin-2
Cytotoxic T-Lymphocytes
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-4
Leukapheresis
Toxicity Tests
Macrophage Colony-Stimulating Factor
National Cancer Institute (U.S.)
Physiologic Monitoring
Clinical Protocols

Keywords

  • Anti-tumor response
  • Intravenous administration
  • Melanoma antigen vaccination
  • Patient monitoring

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. / Panelli, Monica C.; Wunderlich, John; Jeffries, Justin; Wang, Ena; Mixon, Arnold; Rosenberg, Steven A.; Marincola, Francesco M.

In: Journal of Immunotherapy, Vol. 23, No. 4, 07.2000, p. 487-498.

Research output: Contribution to journalArticle

Panelli, Monica C. ; Wunderlich, John ; Jeffries, Justin ; Wang, Ena ; Mixon, Arnold ; Rosenberg, Steven A. ; Marincola, Francesco M. / Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. In: Journal of Immunotherapy. 2000 ; Vol. 23, No. 4. pp. 487-498.
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AU - Mixon, Arnold

AU - Rosenberg, Steven A.

AU - Marincola, Francesco M.

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