Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules

Michael A. Morse, Timothy M. Clay, Amy C. Hobeika, Takuya Osada, Shubi Khan, Stephen (Steve) Chui, Donna Niedzwiecki, Dennis Panicali, Jeffrey Schlom, H. Kim Lyerly

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Purpose: To determine the safety and immunologic and clinical efficacy of a dendritic cell vaccine modified to hyperexpress costimulatory molecules and tumor antigen. Experimental Design: In this phase I study, we administered one or two cycles of four triweekly s.c./intradermal injections of ex vivo generated dendritic cells modified with a recombinant fowlpox vector encoding carcinoembryonic antigen (CEA) and a triad of costimulatory molecules [rF-CEA(6D)-TRICOM]. Controls consisted of immature dendritic cells loaded with tetanus toxoid and a HLA A2 - restricted peptide derived from cytomegalovirus pp65 protein. Results: Fourteen patients (11 with colorectal cancer and 3 with non-small cell lung cancer) were enrolled and 12 completed at least one cycle of immunization. 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 adenopathy that occurred several months after completion of the immunizations. Five other patients were stable through at least one cycle of immunization (3 months). Direct analysis of peripheral blood mononuclear cells using the ELI-Spot assay showed an increase in the frequency of CEA-specific T cells in 10 patients (range, 10-541 CEA-specific cells/105 peripheral blood mononuclear cells). There was a trend for a greater peak frequency of CEA-specific T cells among those with either a minor response or a stable disease following at least one cycle of therapy. A second cycle was not associated with higher T-cell frequencies. Cytokine flow cytometry showed CEA-specific immune response among both CD4+ and CD8+ Tcells in all immune responders. Conclusion: This immunization strategy is safe and activates potent CEA-specific immune responses.

Original languageEnglish (US)
Pages (from-to)3017-3024
Number of pages8
JournalClinical Cancer Research
Volume11
Issue number8
DOIs
StatePublished - Apr 15 2005
Externally publishedYes

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Fowlpox
Carcinoembryonic Antigen
Dendritic Cells
Immunization
T-Lymphocytes
Blood Cells
HLA-A2 Antigen
Intradermal Injections
Tetanus Toxoid
Neoplasm Antigens
Non-Small Cell Lung Carcinoma
Colorectal Neoplasms
Flow Cytometry
Research Design
Vaccines
Cytokines
Safety

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules. / Morse, Michael A.; Clay, Timothy M.; Hobeika, Amy C.; Osada, Takuya; Khan, Shubi; Chui, Stephen (Steve); Niedzwiecki, Donna; Panicali, Dennis; Schlom, Jeffrey; Lyerly, H. Kim.

In: Clinical Cancer Research, Vol. 11, No. 8, 15.04.2005, p. 3017-3024.

Research output: Contribution to journalArticle

Morse, MA, Clay, TM, Hobeika, AC, Osada, T, Khan, S, Chui, SS, Niedzwiecki, D, Panicali, D, Schlom, J & Lyerly, HK 2005, 'Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules', Clinical Cancer Research, vol. 11, no. 8, pp. 3017-3024. https://doi.org/10.1158/1078-0432.CCR-04-2172
Morse, Michael A. ; Clay, Timothy M. ; Hobeika, Amy C. ; Osada, Takuya ; Khan, Shubi ; Chui, Stephen (Steve) ; Niedzwiecki, Donna ; Panicali, Dennis ; Schlom, Jeffrey ; Lyerly, H. Kim. / Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 8. pp. 3017-3024.
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T1 - Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules

AU - Morse, Michael A.

AU - Clay, Timothy M.

AU - Hobeika, Amy C.

AU - Osada, Takuya

AU - Khan, Shubi

AU - Chui, Stephen (Steve)

AU - Niedzwiecki, Donna

AU - Panicali, Dennis

AU - Schlom, Jeffrey

AU - Lyerly, H. Kim

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Y1 - 2005/4/15

N2 - Purpose: To determine the safety and immunologic and clinical efficacy of a dendritic cell vaccine modified to hyperexpress costimulatory molecules and tumor antigen. Experimental Design: In this phase I study, we administered one or two cycles of four triweekly s.c./intradermal injections of ex vivo generated dendritic cells modified with a recombinant fowlpox vector encoding carcinoembryonic antigen (CEA) and a triad of costimulatory molecules [rF-CEA(6D)-TRICOM]. Controls consisted of immature dendritic cells loaded with tetanus toxoid and a HLA A2 - restricted peptide derived from cytomegalovirus pp65 protein. Results: Fourteen patients (11 with colorectal cancer and 3 with non-small cell lung cancer) were enrolled and 12 completed at least one cycle of immunization. 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 adenopathy that occurred several months after completion of the immunizations. Five other patients were stable through at least one cycle of immunization (3 months). Direct analysis of peripheral blood mononuclear cells using the ELI-Spot assay showed an increase in the frequency of CEA-specific T cells in 10 patients (range, 10-541 CEA-specific cells/105 peripheral blood mononuclear cells). There was a trend for a greater peak frequency of CEA-specific T cells among those with either a minor response or a stable disease following at least one cycle of therapy. A second cycle was not associated with higher T-cell frequencies. Cytokine flow cytometry showed CEA-specific immune response among both CD4+ and CD8+ Tcells in all immune responders. Conclusion: This immunization strategy is safe and activates potent CEA-specific immune responses.

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