Preliminary analysis of patients with progressive renal cell carcinoma vaccinated with CA9-peptide-pulsed mature dendritic cells.
Carbonic anhydrase-IXG250/MN (CA9) is a renal cell carcinoma (RCC)-associated antigen ubiquitously expressed in the clear-cell subtype of RCC. Two CA9-derived peptides have been identified defining a cytotoxic T-lymphocyte epitope and human leukocyte antigen (HLA)-DR epitope, able to induce T-cell responses in vitro. A phase I clinical trial was performed with CA9-peptide-loaded dendritic cells (DCs) in patients with progressive, cytokine-refractory metastatic RCC to assess the safety, toxicity, and induction of CA9-specific immunity. Patients with objective progressive metastatic RCC received 5 vaccinations of mature DCs pulsed with the CA9-derived peptides and keyhole limpet hemocyanine (KLH). Peripheral blood was collected at regular intervals, delayed-type hypersensitivity (DTH) was tested at baseline and after the last vaccination, and skin biopsies of positive DTH sites were collected for immunomonitoring purposes. Patients were also monitored for clinical responses. No significant toxicity was observed. All patients developed humoral responses against KLH, and demonstrated DTH conversion. Evaluation of biopsy material suggested an increased influx of T-helper cells. In none of the immunomonitoring assays was evidence for the induction of CA9-peptide-specific immunity observed. No clinical responses were observed. The vaccination of DCs pulsed with KLH and 2 CA9-derived peptides was well tolerated. The lack of induction of CA9-peptide-specific immune responses indicates that this particular vaccine regimen is poor in inducing CA9-peptide-specific immune responses.
Bleumer
Ivar
I
University Medical Center, Nijmegen, The Netherlands.
Tiemessen
Dorien M
DM
Oosterwijk-Wakka
Jeannette C
JC
Völler
Maureen C W
MC
De Weijer
Kim
K
Mulders
Peter F A
PF
Oosterwijk
Egbert
E
D000595:Amino Acid Sequence; D000917:Antibody Formation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000276:immunology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000097:blood / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D007680:Kidney Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy*; D008969:Molecular Sequence Data
D000951:Antigens, Neoplasm; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases