Vaccination with p53 peptide-pulsed dendritic cells is associated with disease stabilization in patients with p53 expressing advanced breast cancer; monitoring of serum YKL-40 and IL-6 as response biomarkers

Autor: Eva Balslev, Anders Elm Pedersen, Svend Saalbach Ottesen, Julia S. Johansen, Kirsten Nikolajsen, Dorte Nielsen, Claus Kamby, Hans Erik Johnsen, Inge Marie Svane, Mogens H. Claesson, Eva Gaarsdal
Rok vydání: 2007
Předmět:
Zdroj: Cancer Immunology, Immunotherapy. 56:1485-1499
ISSN: 1432-0851
0340-7004
DOI: 10.1007/s00262-007-0293-4
Popis: p53 mutations are found in up to 30% of breast cancers and peptides derived from over- expressed p53 protein are presented by class I HLA molecules and may act as tumor-associated epitopes in cancer vaccines. A dendritic cell (DC) based p53 tar- geting vaccine was analyzed in HLA-A2+ patients with progressive advanced breast cancer. DCs were loaded with 3 wild-type and 3 P2 anchor modiWed HLA-A2 binding p53 peptides. Patients received up to 10 sc vac- cinations with 5 £ 10 6 p53-peptide loaded DC with 1- 2 weeks interval. Concomitantly, 6 MIU/m 2 interleu- kine-2 was administered sc. Results from a phase II trial including 26 patients with veriWed progressive breast cancer are presented. Seven patients discontin- ued treatment after only 2-3 vaccination weeks due to rapid disease progression or death. Nineteen patients were available for Wrst evaluation after 6 vaccinations; 8/19 evaluable patients attained stable disease (SD) or minor regression while 11/19 patients had progressive disease (PD), indicating an eVect of p53-speciWc immune therapy. This was supported by: (1) a positive correlation between p53 expression of tumor and observed SD, (2) therapy induced p53 speciWc T cells in 4/7 patients with SD but only in 2/9 patients with PD, and (3) signiWcant response associated changes in serum YKL-40 and IL-6 levels identifying these bio- markers as possible candidates for monitoring of response in connection with DC based cancer immuno- therapy. In conclusion, a signiWcant fraction of breast cancer patients obtained SD during p53-targeting DC therapy. Data encourage initiation of a randomized trial in p53 positive patients evaluating the impact on progression free survival.
Databáze: OpenAIRE