Phase I study of immunization with dendritic cells (DC) modified with recombinant fowlpox encoding carcinoembryonic antigen (CEA) and the triad of costimulatory molecules CD54, CD58, and CD80 (rF-CEA(6D)-TRICOM) in patients with advanced malignancies.

Published

Journal Article

2508 Background: We hypothesize that the activity of vaccines based on DC loaded with tumor antigens will be enhanced by modifications that increase antigen expression and costimulatory activity of the DC. METHODS: In an ongoing phase I study, we are administering 1, 2, or 3 cycles of 4 triweekly subcutaneous / intradermal injections of ex vivo generated DC (5 x 10E6 cells) modified with the recombinant fowlpox vector rF-CEA(6D)-TRICOM (2.5 x 10E7 pfu/5 x 10E7 DC). RESULTS: Thus far, 14 patients have been enrolled into the first 2 cohorts. There were no grade 3/4 toxicities directly referable to the immunizations. One patient had a decrease in the CEA level from 46 to 6.8 and a minor regression in supraclavicular adenopathy that occurred several months after completion of the immunizations. Three other patients were stable through at least 1 cycle of immunization (3 months). Direct analysis of T cells in peripheral blood using the ELISpot assay demonstrated an increase in the frequency of T cells specific for the CEA-expressing vector in 10 of the 12 patients completing participation (range 10 to 541 CEA-specific cells/100,000 peripheral blood mononuclear cells (PBMC).) A greater CEA-specific response was observed for patients with either a minor response or stable disease following at least 1 cycle of therapy compared with those who progressed (mean of 241 vs 50 CEA-specific cells/100,000 PBMC, P=0.03). Cytokine flow cytometry demonstrated that the CEA-specific immune response occurred amongst both CD4 and CD8+ T cells in all responders. Changes in the frequency of CD4+CD25+ regulatory T cells were observed and, in some patients, were inversely correlated with the frequency of CEA-specific CD4+ T cells suggesting that regulatory mechanisms might impact the greatest magnitude of CEA-specific T cells that can be achieved. CONCLUSIONS: This immunization strategy is safe and feasible and activates potent CEA-specific immune responses. This study will continue into the third cohort. [Table: see text].

Full Text

Duke Authors

Cited Authors

  • Morse, M; Clay, T; Hobeika, A; Osada, T; Panicali, D; Lyerly, HK

Published Date

  • July 15, 2004

Published In

Volume / Issue

  • 22 / 14_suppl

Start / End Page

  • 2508 -

PubMed ID

  • 28014999

Pubmed Central ID

  • 28014999

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Language

  • eng

Conference Location

  • United States