Vaccination of patients with metastatic renal cell carcinoma with autologous dendritic cells pulsed with autologous tumor antigens in combination with interleukin-2: a phase 1 study.
Dendritic cells (DC) have been recognized as the most potent antigen presenting cells (APC) of the immune system. We performed a phase 1 study in twelve patients with metastatic renal cell carcinoma (RCC) using autologous immature DC loaded with autologous tumorlysate (TuLy) as a vaccine based on our earlier in vitro observations that such DC can activate tumor-specific cytotoxic T-lymphocytes. The treatment was combined with low-dose interleukin (IL)-2, as this has shown benefit in DC-based therapies. Patients received three intradermal vaccinations at two weekly intervals, and, after each vaccination, IL-2 was administered for 5 consecutive days. In six patients, keyhole-limpet hemocyanin (KLH) was added to the DC culture for immunologic monitoring purposes. In general, DC phenotype was CD14(low), CD86(high), CD40(high), CD80(low), and CD83(low). We noticed that the number of CD14+ cultured DC increased during treatment. Nevertheless, ovalbumin uptake remained high, underlining that these cells were still functional immature DC. The vaccine was able to elicit cellular anti-KLH responses, emphasizing the ability of the injected DC to mount an immunologic response. However, proliferative responses against TuLy were not detected, and humoral responses against TuLy or KLH were absent. Objective clinical responses were not observed, but extended stable disease was noted. The absence of cellular, humoral, or clinical antitumor responses suggests that the vaccination strategy with immature DC has little benefit for patients with advanced RCC. Nevertheless, this study shows the feasibility of a completely autologous DC and tissue culture methodology for the generation of TuLy pulsed DC.
Oosterwijk-Wakka
Jeannette C
JC
Experimental Urology, University Medical Center, 6500 HB Nijmegen, The Netherlands.
Tiemessen
Dorien M
DM
Bleumer
Ivar
I
de Vries
I Jolanda M
IJ
Jongmans
Wim
W
Adema
Gosse J
GJ
Debruyne
Frans M J
FM
de Mulder
Pieter H
PH
Oosterwijk
Egbert
E
Mulders
Peter F A
PF
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D002454:Cell Differentiation; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005240:Feasibility Studies; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007115:Immunization Schedule; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009392:Nephrectomy; D011994:Recombinant Proteins / Q000494:pharmacology; D016896:Treatment Outcome; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007376:Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor