Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial.
Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment with a DC-based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype, and low-dose IL-2 was administered concomitantly. Tumor response, immune response, and serum IL-6 and YKL-40 were measured during treatment. Vaccine generation was successful in all patients and no serious adverse events were observed. None of the patients had an objective response but 13/27 patients obtained disease stabilization (SD) for more than 8 weeks. An antigen-specific immune response was demonstrated in 6/6 patients tested. Furthermore, significant alterations in serum YKL-40 and IL-6 were found during treatment. In conclusion, DC vaccination in our setting is feasible and without severe toxicity. Almost half of the patients obtained SD, and in more than 1/3 of the patients, SD persisted for more than 6 months. However, the evaluation of SD is difficult to interpret in the absence of a randomized trial and, therefore, these results should be interpreted with caution. Antigen-specific immune responses were observed in a subset of the treated patients.
Berntsen
Annika
A
Department of Oncology section, Center for Cancer Immunotherapy, Herlev Hospital, Herlev, Denmark.
Trepiakas
Redas
R
Wenandy
Lynn
L
Geertsen
Poul F
PF
thor Straten
Per
P
Andersen
Mads H
MH
Pedersen
Anders E
AE
Claesson
Mogens H
MH
Lorentzen
Torben
T
Johansen
Julia S
JS
Svane
Inge Marie
IM
D054392:Adipokines; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000556:secondary / Q000628:therapy*; D045744:Cell Line, Tumor; D000071451:Chitinase-3-Like Protein 1; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D016219:Immunotherapy, Adoptive; D051034:Inhibitor of Apoptosis Proteins; D007376:Interleukin-2 / Q000276:immunology / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000473:pathology / Q000628:therapy*; D037102:Lectins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000276:immunology; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019098:Telomerase / Q000276:immunology; D014611:Vaccination
D054392:Adipokines; C107489:BIRC5 protein, human; C084533:CHI3L1 protein, human; D019496:Cancer Vaccines; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D051034:Inhibitor of Apoptosis Proteins; D007376:Interleukin-2; D015850:Interleukin-6; D037102:Lectins; D008869:Microtubule-Associated Proteins; D010455:Peptides; D000077022:Survivin; D019098:Telomerase