PMID- 11731436 OWN - NLM STAT- MEDLINE DCOM- 20020103 LR - 20201215 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 61 IP - 23 DP - 2001 Dec 1 TI - Vaccination of pediatric solid tumor patients with tumor lysate-pulsed dendritic cells can expand specific T cells and mediate tumor regression. PG - 8513-9 AB - Dendritic cells (DCs) have been shown to be a promising adjuvant for inducing immunity to cancer. We evaluated tumor lysate-pulsed DC in a Phase I trial of pediatric patients with solid tumors. Children with relapsed solid malignancies who had failed standard therapies were eligible. The vaccine used immature DC (CD14-, CD80+, CD86+, CD83-, and HLA-DR+) generated from peripheral blood monocytes in the presence of granulocyte/monocyte colony-stimulating factor and interleukin-4. These DC were then pulsed separately with tumor cell lysates and the immunogenic protein keyhole limpet hemocyanin (KLH) for 24 h and then combined. A total of 1 x 10(6) to 1 x 10(7) DC are administered intradermally every 2 weeks for a total of three vaccinations. Fifteen patients (ages 3-17 years) were enrolled with 10 patients completing all vaccinations. Leukapheresis yields averaged 2.8 x 10(8) peripheral blood mononuclear cells (PBMC)/kg, and DC yields averaged 10.9% of starting PBMC. Patients with neuroblastoma, sarcoma, and renal malignancies were treated without obvious toxicity. Delayed-type hypersensitivity (DTH) response was detected in 7 of 10 patients for KLH and 3 of 6 patients for tumor lysates. Priming of T cells to KLH was seen in 6 of 10 patients and to tumor in 3 of 7 patients as demonstrated by specific IFN-gamma-secreting T cells in unstimulated PBMCs. Significant regression of multiple metastatic sites was seen in 1 patient. Five patients showed stable disease, including 3 who had minimal disease at time of vaccine therapy and remain free of tumor with 16-30 months follow-up. Our results demonstrate that it is feasible to generate large numbers of functional DC from pediatric patients even in those highly pretreated and with a large tumor burden. The DC can be administered in an outpatient setting without any observable toxicity. Most importantly, we have demonstrated the ability of the tumor lysate/KLH-pulsed DC to generate specific T-cell responses and to elicit regression of metastatic disease. FAU - Geiger, J D AU - Geiger JD AD - Department of Surgery, Section of Pediatric Surgery, Section of General Surgery, the Tumor Immunology and Immunotherapy Program, Ann Arbor, Michigan 48109-0245, USA. jgeiger@umich.edu FAU - Hutchinson, R J AU - Hutchinson RJ FAU - Hohenkirk, L F AU - Hohenkirk LF FAU - McKenna, E A AU - McKenna EA FAU - Yanik, G A AU - Yanik GA FAU - Levine, J E AU - Levine JE FAU - Chang, A E AU - Chang AE FAU - Braun, T M AU - Braun TM FAU - Mule, J J AU - Mule JJ LA - eng GR - 1-R29-CA-77471-01/CA/NCI NIH HHS/United States GR - 5PO1 CA 59327/CA/NCI NIH HHS/United States GR - MO1-RR00042/RR/NCRR NIH HHS/United States GR - T32-CA-09672/CA/NCI NIH HHS/United States PT - Clinical Trial PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 82115-62-6 (Interferon-gamma) RN - 9013-72-3 (Hemocyanins) RN - FV4Y0JO2CX (keyhole-limpet hemocyanin) SB - IM MH - Adolescent MH - Child MH - Child, Preschool MH - Dendritic Cells/*immunology MH - Female MH - Hemocyanins/immunology MH - Humans MH - Hypersensitivity, Delayed/immunology MH - *Immunotherapy, Adoptive MH - Interferon-gamma/metabolism MH - Leukapheresis MH - Male MH - Neoplasms/*immunology/*therapy MH - T-Lymphocytes/*immunology/metabolism MH - Vaccination EDAT- 2001/12/04 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/12/04 10:00 PHST- 2001/12/04 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/12/04 10:00 [entrez] PST - ppublish SO - Cancer Res. 2001 Dec 1;61(23):8513-9.