Immunotherapy of cancer with dendritic-cell-based vaccines |
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Authors: | E Gilboa Smita K Nair H Kim Lyerly |
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Institution: | (1) Center for Genetic and Cellular Therapies, Department of Surgery, Box 2601, Duke University Medical Center, Durham, NC 27710, USA e-mail: gilbo001@mc.duke.edu Fax: +1 919 681 7970, US |
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Abstract: | Animal studies have shown that vaccination with genetically modified tumor cells or with dendritic cells (DC) pulsed with
tumor antigens are potent strategies to elicit protective immunity in tumor-bearing animals, more potent than “conventional”
strategies that have been tested in clinical settings with limited success. While both vaccination strategies are forms of
cell therapy requiring complex and costly ex vivo manipulations of the patient’s cells, current protocols using dendritic
cells are considerably simpler and would be more widely available. Vaccination with defined tumor antigens presented by DC
has obvious appeal. However, in view of the expected emergence of antigen-loss variants as well as natural immunovariation,
effective vaccine formulations must contain mixtures of commonly, if not universally, expressed tumor antigens. When, or even
if, such common tumor antigens will be identified cannot be, predicted, however. Thus, for the foreseeable future, vaccination
with total-tumor-derived material as source of tumor antigens may be preferable to using defined tumor antigens. Vaccination
with undefined tumor-derived antigens will be limited, however, by the availability of sufficient tumor tissue for antigen
preparation. Because the mRNA content of single cells can be amplified, tumor mRNA, or corresponding cDNA libraries, offer
an unlimited source of tumor antigens. DC transfected with tumor RNA were shown to engender potent antitumor immunity in animal
studies. Thus, immunotherapy using autologous DC loaded with unfractionated tumor-derived antigens in the form of RNA emerges
as a potentially powerful and broadly useful vaccination strategy for cancer patients.
Received: 10 October 1997 / Accepted: 12 January 1998 |
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Keywords: | Dendritic cells Vaccines Immunotherapy Tumor antigens Tumor mRNA |
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