Dendritic cells (DCs) are potent antigen-presenting cells that have the ability to stimulate primary T cell antitumor immune responses in animals and humans. Since the first published clinical trial of dendritic cell vaccination in 1995, 98 studies describing more than 1000 vaccinees have been published in peer-reviewed medical journals or presented at the annual meetings of the American Society for Clinical Oncology, the American Association of Cancer Research, or the American Society of Hematology. Trials have been performed in 15 countries. Trials included patients with more than two dozen tumor types; most trials studied patients with malignant melanoma, prostate cancer, colorectal carcinoma, or multiple myeloma, using autologous DCs pulsed with synthetic antigens or idiotype antibodies. The DC vaccines were also prepared by pulsing DCs with tumor lysates or RNA, by transfection with tumor DNA, or by creating tumor cell/DC fusions. Various approaches to vaccine cell numbers, length of vaccine program, site of vaccination, frozen preservation of vaccine, and use of a maturations step for DCs were used. Adverse effects associated with DC vaccination were uncommon; most were mild and self-limited and none were serious. Clinical responses were observed in approximately half the trials. The DC vaccination may provide a safe approach to cancer immunotherapy that can overcome the limited reach and immunogenicity of peptide vaccines.

Marrow and peripheral blood cells from nine children with juvenile chronic granulocytic leukemia (JCGL) demonstrated intense (94±16% maximum) spontaneous granulocyte/macrophage colony growth but cells from five children with the adult variety of CGL did not. This unusual pattern of colony growth depended upon a stimulatory protein(s) produced by mononuclear phagocytes. No GM-CSA activity was found in any chromatofocused fraction of JCGL monocyte-conditioned media but an activity that induced GM-CSA in umbilical vein endothelial cells was detected at pI 6.9-7.2. Moreover, the CSA-inducing monokine was neutralized by an anti-IL-i antibody in vitro and, in the one case so tested, the same antibody also inhibited "spontaneous" colony growth. Therefore granulocyte/macrophage colony growth in JCGL is characteristically abnormal and distinguishes JCGL from the adult form of the disease. This abnormality depends upon the production, by mononuclear phagocytes, of IL-1 which, in turn, stimulates the release of high levels of colony stimulating activity by other cells. The high proliferative activity of CFU-GM we found in JCGL patients, and the high levels of GM-CSA found in their serum are compatible with the view that the in vitro abnormality reflects a similar abnormality in vivo.

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Active immunization against measles, Haemophilus influenza B, tetanus, diphtheria, hepatitis B, influenza, poliomyelitis, and, when indicated varicella and pneumococcus induces long-lasting immunologic protection in most healthy pediatric vaccine recipients. Among children receiving immunosuppressive therapy for cancer, possible early loss of specific immunity acquired from prior vaccination or disease, and likely diminished responsiveness to initial or booster vaccination must be considered. In addition, the safety of vaccine administration requires separate study in this population. Published evidence demonstrates preservation of vaccine-induced antibody titers against tetanus, diphtheria, poliomyelitis and (in children treated for lymphoma) pneumococcus. In contrast, prior immunity to varicella, influenza, and hepatitis B (when naturally acquired), and measles (acquired by vaccination) is compromised during and/or after antineoplastic therapy. Studies of immunologic protection acquired by prior vaccination against hepatitis B, varicella, and H influenza have not been published. The safety of administering toxoids and inactivated vaccines in this population is well documented. In contrast, morbidity must be expected if live attenuated vaccines (oral polio vaccine, attenuated measles vaccine or attenuated varicella vaccine) are administered to children receiving anti-cancer therapy. The risks of using live vaccines should be measured against demonstrable benefits in any vaccine program. The response to initial or booster immunizations against tetanus and diphtheria are similar to those in healthy children. For all other immunizations reviewed, responsiveness is diminished during periods of chemotherapy, more strikingly in children treated for leukemia than for solid tumors. Antibody responses to these vaccines range from slightly blunted (in the case of H influenza B) to marginal (influenza) or completely useless (pneumococcus and hepatitis B in children treated for leukemia).