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A Phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen.

Publication ,  Journal Article
Morse, MA; Deng, Y; Coleman, D; Hull, S; Kitrell-Fisher, E; Nair, S; Schlom, J; Ryback, ME; Lyerly, HK
Published in: Clin Cancer Res
June 1999

Dendritic cells (DCs), antigen-presenting cells capable of priming naive T cells to specific antigens in an HLA-restricted fashion, have been demonstrated to induce protective T cell-mediated immunity in tumor-bearing animals. We performed this study to test the safety, feasibility, and clinical response of immunizations with in vitro-generated DCs, loaded with an HLA-A2-restricted peptide fragment of the tumor antigen carcinoembryonic antigen (CEA), for the treatment of patients with advanced CEA-expressing malignancies. Cell preparations enriched for autologous DCs were generated from the patients' plastic adherent peripheral blood mononuclear cells in serum-free media supplemented with granulocyte macrophage colony-stimulating factor and interleukin-4. Within the cell preparation, 66% of the cells expressed the phenotype typical for DCs (CD86high, HLA-DRhigh, and CD14low). The DCs were loaded with the CEA peptide CAP-1 and cryopreserved. Groups of three to six patients received four weekly or biweekly i.v. infusions of the CAP-1-loaded DC in escalating dose levels of 1 x 10(7), 3 x 10(7), and 1 x 10(8) cells/dose. A subset of the patients in the last group also received intradermal injections of 1 x 10(6) DCs. There were no toxicities directly referable to the treatments. One patient had a minor response, and one had stable disease. Skin punch biopsy at DC injection sites demonstrated pleomorphic infiltrates in the three patients evaluated. We conclude that it is feasible and safe to generate and administer large numbers of previously cryopreserved DCs loaded with CAP-1 peptide to patients with advanced malignancies.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

June 1999

Volume

5

Issue

6

Start / End Page

1331 / 1338

Location

United States

Related Subject Headings

  • Transplantation, Autologous
  • Survival Rate
  • Rheumatoid Factor
  • Peptide Fragments
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Male
  • Immunotherapy, Active
  • Humans
 

Citation

APA
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ICMJE
MLA
NLM
Morse, M. A., Y. Deng, D. Coleman, S. Hull, E. Kitrell-Fisher, S. Nair, J. Schlom, M. E. Ryback, and H. K. Lyerly. “A Phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen.Clin Cancer Res 5, no. 6 (June 1999): 1331–38.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

June 1999

Volume

5

Issue

6

Start / End Page

1331 / 1338

Location

United States

Related Subject Headings

  • Transplantation, Autologous
  • Survival Rate
  • Rheumatoid Factor
  • Peptide Fragments
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Male
  • Immunotherapy, Active
  • Humans