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Clinical applications of dendritic cell vaccination in the treatment of cancer

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Abstract

Dendritic cell (DC) immunotherapy has shown significant promise in animal studies as a potential treatment for cancer. Its application in the clinic depends on the results of human trials. Here, we review the published clinical trials of cancer immunotherapy using exogenously antigen-exposed DCs. We begin with a short review of general properties and considerations in the design of such vaccines. We then review trials by disease type. Despite great efforts on the part of individual investigative groups, most trials to date have not yielded data from which firm conclusions can be drawn. The reasons for this include nonstandard DC preparation and vaccination protocols, use of different antigen preparations, variable means of immune assessment, and nonrigorous criteria for defining clinical response. While extensive animal studies have been conducted using DCs, optimal parameters in humans remain to be established. Unanswered questions include optimal cell dose, use of mature versus immature DCs for vaccination, optimal antigen preparation, optimal route, and optimal means of assessing immune response. It is critical that these questions be answered, as DC therapy is labor- and resource-intensive. Cooperation is needed on the part of the many investigators in the field to address these issues. If such cooperation is not forthcoming, the critical studies that will be required to make DC therapy a clinically and commercially viable enterprise will not take place, and this therapy, so promising in preclinical studies, will not be able to compete with the many other new approaches to cancer therapy presently in development. Trials published in print through June 2003 are included. We exclude single case reports, except where relevant, and trials with so many variables as to prevent interpretation about DC therapy effects.

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Abbreviations

CEA:

carcinoembryonic antigen

CTL:

cytotoxic T lymphocyte

DC:

dendritic cell

DTH:

delayed-type hypersensitivity

EpCAM:

epithelial cell adhesion molecule

FCS:

fetal calf serum

Flt3L:

Flt3 ligand

G-CSF:

granulocyte colony stimulating factor

GM-CSF:

granulocyte-macrophage colony stimulating factor

HBsAg:

hepatitis B surface antigen

HLA:

human leukocyte antigen

HPV:

human papillomavirus

IFN:

interferon

Ig:

immunoglobulin

IL:

interleukin

KLH:

keyhole limpet hemocyanin

MHC:

major histocompatibility complex

MUC1:

mucin gene antigen

PAP:

prostatic acid phosphatase

PBMC:

peripheral blood mononuclear cell

PEG:

polyethylene glycol

PSA:

prostate-specific antigen

PSMA:

prostate-specific membrane antigen

PTH:

parathyroid hormone

RT-PCR:

reverse transcription polymerase chain reaction

TNF-α:

tumor necrosis factor α

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  1. Department of Hematology and Oncology, The Arizona Cancer Center, University of Arizona/University Medical Center, 1515 N. Campbell Ave., Tucson, AZ 85724, USA

    Lee D. Cranmer, Katrina T. Trevor & Evan M. Hersh

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  1. Lee D. Cranmer
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Cranmer, L.D., Trevor, K.T. & Hersh, E.M. Clinical applications of dendritic cell vaccination in the treatment of cancer. Cancer Immunol Immunother 53, 275–306 (2004). https://doi.org/10.1007/s00262-003-0432-5

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