Dendritic cell (DC) products for cancer patient therapy are being used in clinical trials to enhance anti-tumor immune responses,
which are often compromised in patients with advanced disease. DC therapies are also being used in patients with post-transplant
graft versus host disease (GVHD) or patients with infectious diseases.15,16,18 Studies in animal models of autoimmunity suggest that in the future, adoptive transfers of tolerogenic DCs may be beneficial
to patients with autoimmunity.17 DC-based therapies are nontoxic, but their clinical efficacy has not been confirmed.54 In part, this result might reflect the complexity of DC production processes and the lack of universal criteria for quality
and release of therapeutic DC products. Currently, manufactured DC products are phenotypically and functionally variable,
and products made in different laboratories are not comparable. Although this might be due to the source and functional competence
of DC precursors in cancer patients, differences in production methods clearly contribute to DC product variability. To standardize
DC production, several manufacturing issues must be addressed, including the selection of media and conditions for DC culture,
the composition of maturation cytokines, and the choice and standardization of assays used.
As more information is being generated about the biologic characteristics of DCs, significant changes in the manufacturing
process are being made. At the same time, DC products generated for therapy must meet predefined criteria for sterility, viability,
purity, and stability. These products also must be defined phenotypically and functionally, and strict attention should be
paid to their activation and maturation status, as those characteristics likely correlate with clinical endpoints.
Reliable production of biologically active, clinically effective DC products with defined potency will require modifications
of current methods, including the use of semi-automatic culture devices for clinical-scale production, the addition of novel
cytokines, and the introduction of improved antigen uptake methods. Equally important to the future success of DC-based therapies
is monitoring of patients' immune responses after vaccination. Immune monitoring of DC-based cancer vaccines is essential
for establishing correlations between clinical endpoints and tumor-specific as well as vaccine-specific immunity. Although
elusive, such correlations have been increasingly frequently reported in recent cancer vaccination trials,55,56 perhaps because of more sophisticated vaccine designs or improved quality of immune monitoring. Today, many ex vivo assays are available to be used as monitoring tools, and the selection of a robust assay that will reliably measure the frequency
and/or activity of epitope-specific T cells in the peripheral circulation or patients' body fluids is critical for success.
In general, recent emphasis has been on measuring tumor antigen-specific humoral and cellular responses in single cell assays.
These and other DC functional assays represent a special challenge, because specimen cryopreservation and batching used in
serial monitoring often interfere with cellular functions. Standardization and the selection of robust, reliable monitoring
methods used in the setting of an established quality control program are the key to successful evaluations of DC-based cancer
Theresa L. Whiteside, PhD, is a professor at the University of Pittsburgh Cancer Institute and director of the Immunologic Monitoring and Cellular Products
Laboratory (IMCPL), Pittsburgh, PA, 412.624.0096, email@example.com