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.

Inge Marie Svane; Anders E Pedersen; Julia S Johansen; Hans E Johnsen; Dorte Nielsen; Claus Kamby; Svend Ottesen; Eva Balslev; Eva Gaarsdal; Kirsten Nikolajsen; Mogens H Claesson

doi:10.1007/s00262-007-0293-4

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.

Inge Marie Svane, Anders E Pedersen, Julia S Johansen, Hans E Johnsen, Dorte Nielsen, Claus Kamby, Svend Ottesen, Eva Balslev, Eva Gaarsdal, Kirsten Nikolajsen, Mogens H Claesson

Department of Immunology and Microbiology

77 Citations (Scopus)

Abstract

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 targeting vaccine was analyzed in HLA-A2+ patients with progressive advanced breast cancer. DCs were loaded with 3 wild-type and 3 P2 anchor modified HLA-A2 binding p53 peptides. Patients received up to 10 sc vaccinations with 5 x 10(6) p53-peptide loaded DC with 1-2 weeks interval. Concomitantly, 6 MIU/m(2) interleukine-2 was administered sc. Results from a phase II trial including 26 patients with verified progressive breast cancer are presented. Seven patients discontinued treatment after only 2-3 vaccination weeks due to rapid disease progression or death. Nineteen patients were available for first 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 effect of p53-specific immune therapy. This was supported by: (1) a positive correlation between p53 expression of tumor and observed SD, (2) therapy induced p53 specific T cells in 4/7 patients with SD but only in 2/9 patients with PD, and (3) significant response associated changes in serum YKL-40 and IL-6 levels identifying these biomarkers as possible candidates for monitoring of response in connection with DC based cancer immunotherapy. In conclusion, a significant 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.

Original language	English
Journal	Cancer Immunology, Immunotherapy
Volume	56
Issue number	9
Pages (from-to)	1485-99
Number of pages	14
ISSN	0340-7004
DOIs	https://doi.org/10.1007/s00262-007-0293-4
Publication status	Published - 2007

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Svane, I. M., Pedersen, A. E., Johansen, J. S., Johnsen, H. E., Nielsen, D., Kamby, C., Ottesen, S., Balslev, E., Gaarsdal, E., Nikolajsen, K., & Claesson, M. H. (2007). 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. Cancer Immunology, Immunotherapy, 56(9), 1485-99. https://doi.org/10.1007/s00262-007-0293-4

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. / Svane, Inge Marie; Pedersen, Anders E; Johansen, Julia S et al.

In: Cancer Immunology, Immunotherapy, Vol. 56, No. 9, 2007, p. 1485-99.

Research output: Contribution to journal › Journal article › Research › peer-review

Svane, IM, Pedersen, AE, Johansen, JS, Johnsen, HE, Nielsen, D, Kamby, C, Ottesen, S, Balslev, E, Gaarsdal, E, Nikolajsen, K & Claesson, MH 2007, '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.', Cancer Immunology, Immunotherapy, vol. 56, no. 9, pp. 1485-99. https://doi.org/10.1007/s00262-007-0293-4

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title = "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.",

abstract = "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 targeting vaccine was analyzed in HLA-A2+ patients with progressive advanced breast cancer. DCs were loaded with 3 wild-type and 3 P2 anchor modified HLA-A2 binding p53 peptides. Patients received up to 10 sc vaccinations with 5 x 10(6) p53-peptide loaded DC with 1-2 weeks interval. Concomitantly, 6 MIU/m(2) interleukine-2 was administered sc. Results from a phase II trial including 26 patients with verified progressive breast cancer are presented. Seven patients discontinued treatment after only 2-3 vaccination weeks due to rapid disease progression or death. Nineteen patients were available for first 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 effect of p53-specific immune therapy. This was supported by: (1) a positive correlation between p53 expression of tumor and observed SD, (2) therapy induced p53 specific T cells in 4/7 patients with SD but only in 2/9 patients with PD, and (3) significant response associated changes in serum YKL-40 and IL-6 levels identifying these biomarkers as possible candidates for monitoring of response in connection with DC based cancer immunotherapy. In conclusion, a significant 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.",

author = "Svane, {Inge Marie} and Pedersen, {Anders E} and Johansen, {Julia S} and Johnsen, {Hans E} and Dorte Nielsen and Claus Kamby and Svend Ottesen and Eva Balslev and Eva Gaarsdal and Kirsten Nikolajsen and Claesson, {Mogens H}",

note = "Keywords: Adult; Aged; Breast Neoplasms; Cancer Vaccines; Dendritic Cells; Female; Glycoproteins; Humans; Interleukin-6; Middle Aged; Peptide Fragments; Tumor Markers, Biological; Tumor Suppressor Protein p53; Vaccination",

year = "2007",

doi = "10.1007/s00262-007-0293-4",

language = "English",

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pages = "1485--99",

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T1 - 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.

AU - Svane, Inge Marie

AU - Pedersen, Anders E

AU - Johansen, Julia S

AU - Johnsen, Hans E

AU - Nielsen, Dorte

AU - Kamby, Claus

AU - Ottesen, Svend

AU - Balslev, Eva

AU - Gaarsdal, Eva

AU - Nikolajsen, Kirsten

AU - Claesson, Mogens H

N1 - Keywords: Adult; Aged; Breast Neoplasms; Cancer Vaccines; Dendritic Cells; Female; Glycoproteins; Humans; Interleukin-6; Middle Aged; Peptide Fragments; Tumor Markers, Biological; Tumor Suppressor Protein p53; Vaccination

PY - 2007

Y1 - 2007

N2 - 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 targeting vaccine was analyzed in HLA-A2+ patients with progressive advanced breast cancer. DCs were loaded with 3 wild-type and 3 P2 anchor modified HLA-A2 binding p53 peptides. Patients received up to 10 sc vaccinations with 5 x 10(6) p53-peptide loaded DC with 1-2 weeks interval. Concomitantly, 6 MIU/m(2) interleukine-2 was administered sc. Results from a phase II trial including 26 patients with verified progressive breast cancer are presented. Seven patients discontinued treatment after only 2-3 vaccination weeks due to rapid disease progression or death. Nineteen patients were available for first 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 effect of p53-specific immune therapy. This was supported by: (1) a positive correlation between p53 expression of tumor and observed SD, (2) therapy induced p53 specific T cells in 4/7 patients with SD but only in 2/9 patients with PD, and (3) significant response associated changes in serum YKL-40 and IL-6 levels identifying these biomarkers as possible candidates for monitoring of response in connection with DC based cancer immunotherapy. In conclusion, a significant 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.

AB - 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 targeting vaccine was analyzed in HLA-A2+ patients with progressive advanced breast cancer. DCs were loaded with 3 wild-type and 3 P2 anchor modified HLA-A2 binding p53 peptides. Patients received up to 10 sc vaccinations with 5 x 10(6) p53-peptide loaded DC with 1-2 weeks interval. Concomitantly, 6 MIU/m(2) interleukine-2 was administered sc. Results from a phase II trial including 26 patients with verified progressive breast cancer are presented. Seven patients discontinued treatment after only 2-3 vaccination weeks due to rapid disease progression or death. Nineteen patients were available for first 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 effect of p53-specific immune therapy. This was supported by: (1) a positive correlation between p53 expression of tumor and observed SD, (2) therapy induced p53 specific T cells in 4/7 patients with SD but only in 2/9 patients with PD, and (3) significant response associated changes in serum YKL-40 and IL-6 levels identifying these biomarkers as possible candidates for monitoring of response in connection with DC based cancer immunotherapy. In conclusion, a significant 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.

U2 - 10.1007/s00262-007-0293-4

DO - 10.1007/s00262-007-0293-4

M3 - Journal article

C2 - 17285289

SN - 0340-7004

VL - 56

SP - 1485

EP - 1499

JO - Cancer Immunology, Immunotherapy

JF - Cancer Immunology, Immunotherapy

IS - 9

ER -