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In Reply:

Human Immune Therapy Center, University of Virginia, Charlottesville, VA

There is convincing evidence that immune responses to cancer occur spontaneously in humans,¹ and that immune surveillance affects cancer progression.² Dramatic tumor regressions have been observed in a minority of patients with each of various immunologic therapies for cancer, including the trial of a multipeptide vaccine we have reported.³ Thus, there is substantial basis for continuing to develop cancer vaccines. Except for vaccines targeting oncogenic viruses, optimal cancer vaccine approaches remain to be defined.

In our previous article,³ we found that vaccination with multiple peptides in an emulsion of granulocyte macrophage colony-stimulating factor in adjuvant was immunogenic, and that vaccination with the same peptides pulsed on monocyte-derived immature dendritic cells (DCs) was only weakly immunogenic. In that article, we were careful not to recommend against future development of DC vaccines, but we did conclude that the data support continued investigation of vaccination with peptides administered in granulocyte macrophage colony-stimulating factor in adjuvant.

As stated in our Discussion, we agree with Adams, O'Neill, and Bhardwaj, that different DC preparations may be more effective than immature DCs. It is widely accepted that DCs are critical to the control of immunity and tolerance.⁴ However, the degree to which immunity or tolerance is induced following vaccination may depend on multiple factors, including maturation. Thus, success or failure of cancer vaccines will depend on improved characterization of optimal DCs in vitro and in vivo. There is a great deal to learn about normal DC physiology in vivo, and also about the pathophysiology of the disturbed host-tumor relationship in cancer patients. Investigations of DCs in vaccine strategies should certainly continue. At our institution, we, and our collaborators, are investigating DC accumulation and maturation status at vaccine sites and in draining nodes, as well as molecular mediators of tolerance by DC. These studies may aid in design of future vaccines, either using direct injection of antigen for uptake by DC, or for vaccines using DCs generated exogenously. It is not possible at this time to define the best approach for future vaccines. Thus, it is critical that investigation continue simultaneously in multiple promising areas.

Author's Disclosures of Potential Conflicts of Interest

The author indicated no potential conflicts of interest.

REFERENCES

1. Yamshchikov G, Thompson L, Ross WG, et al: Analysis of a natural immune response against tumor antigens in a melanoma survivor: Lessons applicable to clinical trial evaluations. Clin Cancer Res 7:909–916, 2001[Abstract/Free Full Text]

2. Shankaran V, Ikeda H, Bruce AT, et al: IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410:1107–1111, 2001[CrossRef][Medline]

3. Slingluff CL, Petroni GR, Yamshchikov GV, et al: Clinical and immunologic results of a ranomized phase II trial of vaccination using four melanoma peptides either administered in granulocyte macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells. J Clin Oncol 21:4016–4026, 2003[Abstract/Free Full Text]

4. Munn DH, Sharma MD, Lee JR, et al: Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 297:1867–1870, 2002[Abstract/Free Full Text]

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Related Article

• Clinical and Immunologic Results of a Randomized Phase II Trial of Vaccination Using Four Melanoma Peptides Either Administered in Granulocyte-Macrophage Colony-Stimulating Factor in Adjuvant or Pulsed on Dendritic Cells
  Craig L. Slingluff, Jr, Gina R. Petroni, Galina V. Yamshchikov, Donna L. Barnd, Shannon Eastham, Holly Galavotti, James W. Patterson, Donna H. Deacon, Sarah Hibbitts, David Teates, Patrice Y. Neese, William W. Grosh, Kimberly A. Chianese-Bullock, Elizabeth M.H. Woodson, Catherine J. Wiernasz, Priscilla Merrill, Jennifer Gibson, Maureen Ross, and Victor H. Engelhard
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Related Correspondence

• Maturation Matters: Importance of Maturation for Antitumor Immunity of Dendritic Cell Vaccines
  Sylvia Adams, David O'Neill, and Nina Bhardwaj
  JCO 2004 22: 3834-3835 [Full Text]

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