Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

9
Dendritic Cells and Cancer: Prospects for Cancer Vaccination
Derek N. J. Hart, David Jackson and Frank Nestle
9.1
Introduction
Effective therapeutic cancer vaccination is an old dream, now rekindled by modern
advances in cell biology and immunology. Several key facts have inspired the current
optimism for clinical immunotherapy trials. First, the realization that, by definition,
every malignant cell must express at least one gene product in an abnormal fashion
means that theoretically there is at least one tumor-associated antigen (TAA) (it may
be an autoantigen) available as a target. Secondly, we now know that any cellular protein
(membrane, cytoplasmic or nuclear) may be presented as a peptide, in the context
of major histocompatibility complex (MHC) molecules, for recognition by the T
lymphocyte receptor complex. Thirdly, whilst it is clear that the immune response
has failed the cancer patient, it is also true that it has not suffered irreversible meltdown,
i. e. deletion of tumor-reactive T lymphocytes. Finally, it is now recognized
that dendritic cells (DCs) are the key cellular elements for initiating and directing
immune responses. As DC biology appears to be abnormal in cancer patients, the
simplest hypothesis of the day is to use activated DCs to present relevant TAAs to
the patient's immune system and thus generate an effective therapeutic response.
This chapter will review the physiology of DC biology in the cancer patient, DC preparations
and clinical trial results, whilst predicting areas requiring attention in order
to optimize DC cancer vaccination for future patient benefit.
9.2
DC Properties
Cancer Immune Therapie: Current and Future Strategies
Edited by G. Stuhler and P. Walden
Copyright # 2002 Wiley-VCH Verlag GmbH & Co. KGaA
ISBNs: 3-527-30441-X (Hardback); 3-527-60079-5
(Electronic)
DCs originate from CD34 + hematopoietic stem cells, circulate in peripheral blood
and are found in virtually all tissues of the body. In peripheral blood, DCs are a morphologically
heterogeneous cell population, including DCs with membrane processes
(ªmyeloid DCº) and DCs with plasmacytoid morphology (ªplasmacytoid
monocytesº, ªplasmacytoid T lymphocyteº, ªlymphoid DCsº) [1, 2]. In the skin, DCs
are present as epidermal Langerhans cells (LCs) with their characteristic Birbeck
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