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Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146-154 peptide.
Cancer Immunol Immunother. 2006 Sep; 55(9):1033-42.CI

Abstract

T cell immunotherapy of prostate cancer (CaP) offers the potential for less toxic, more effective outcomes. A clinical trial was conducted in 28 patients with locally advanced or metastatic CaP to determine whether an HLA-A2 binding epitope of prostate-specific antigen, PSA146-154 (PSA-peptide), can induce specific T cell immunity. Patients were vaccinated either by intradermal injection of PSA-peptide and GM-CSF or by intravenous administration of autologous dendritic cells pulsed with PSA-peptide at weeks 1, 4 and 10. Delayed-type hypersensitivity (DTH) skin testing was performed at weeks 4, 14, 26 and 52. Fifty percent of the patients developed positive DTH responses to PSA-peptide. The size of the DTH induration progressively increased over time in the majority of responding patients. Skin biopsies from seven DTH-positive patients were available and T cells that developed in situ were also characterized. The phenotype of recovered T cells demonstrated variable proportions of CD4+CD8-, CD4-CD8+ and CD4+CD8+ T cell populations. Cytokine analysis of PSA-peptide stimulated T cells per bead array assay exhibited specific IFN-gamma and TNF-alpha response in six of seven patients. Specific IL-4 response was observed in five patients, while IL-10 response was detected in one patient. Purified CD4-CD8+ T cells isolated from four patients demonstrated specific cytolytic activity per chromium release assay. In conclusion, immunization with PSA-peptide induced specific T cell immunity in one-half of the patients with locally advanced and hormone-sensitive, metastatic CaP. DTH-derived T cells exhibited PSA-peptide-specific cytolytic activity and predominantly expressed a type-1 cytokine profile.

Authors+Show Affiliations

Department of Medicine, Section of Hematology/Oncology, University of Illinois, Room 3150, Molecular Biology Research Building, 900 South Ashland Avenue, Chicago, IL 60607, USA. speramba@uic.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase I
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

16283303

Citation

Perambakam, Supriya, et al. "Induction of Specific T Cell Immunity in Patients With Prostate Cancer By Vaccination With PSA146-154 Peptide." Cancer Immunology, Immunotherapy : CII, vol. 55, no. 9, 2006, pp. 1033-42.
Perambakam S, Hallmeyer S, Reddy S, et al. Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146-154 peptide. Cancer Immunol Immunother. 2006;55(9):1033-42.
Perambakam, S., Hallmeyer, S., Reddy, S., Mahmud, N., Bressler, L., DeChristopher, P., Mahmud, D., Nunez, R., Sosman, J. A., & Peace, D. J. (2006). Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146-154 peptide. Cancer Immunology, Immunotherapy : CII, 55(9), 1033-42.
Perambakam S, et al. Induction of Specific T Cell Immunity in Patients With Prostate Cancer By Vaccination With PSA146-154 Peptide. Cancer Immunol Immunother. 2006;55(9):1033-42. PubMed PMID: 16283303.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146-154 peptide. AU - Perambakam,Supriya, AU - Hallmeyer,Sigrun, AU - Reddy,Samarth, AU - Mahmud,Nadim, AU - Bressler,Linda, AU - DeChristopher,Phillip, AU - Mahmud,Delores, AU - Nunez,Rafael, AU - Sosman,Jeffrey A, AU - Peace,David J, Y1 - 2005/11/10/ PY - 2005/05/25/received PY - 2005/10/03/accepted PY - 2005/11/12/pubmed PY - 2006/8/22/medline PY - 2005/11/12/entrez SP - 1033 EP - 42 JF - Cancer immunology, immunotherapy : CII JO - Cancer Immunol. Immunother. VL - 55 IS - 9 N2 - T cell immunotherapy of prostate cancer (CaP) offers the potential for less toxic, more effective outcomes. A clinical trial was conducted in 28 patients with locally advanced or metastatic CaP to determine whether an HLA-A2 binding epitope of prostate-specific antigen, PSA146-154 (PSA-peptide), can induce specific T cell immunity. Patients were vaccinated either by intradermal injection of PSA-peptide and GM-CSF or by intravenous administration of autologous dendritic cells pulsed with PSA-peptide at weeks 1, 4 and 10. Delayed-type hypersensitivity (DTH) skin testing was performed at weeks 4, 14, 26 and 52. Fifty percent of the patients developed positive DTH responses to PSA-peptide. The size of the DTH induration progressively increased over time in the majority of responding patients. Skin biopsies from seven DTH-positive patients were available and T cells that developed in situ were also characterized. The phenotype of recovered T cells demonstrated variable proportions of CD4+CD8-, CD4-CD8+ and CD4+CD8+ T cell populations. Cytokine analysis of PSA-peptide stimulated T cells per bead array assay exhibited specific IFN-gamma and TNF-alpha response in six of seven patients. Specific IL-4 response was observed in five patients, while IL-10 response was detected in one patient. Purified CD4-CD8+ T cells isolated from four patients demonstrated specific cytolytic activity per chromium release assay. In conclusion, immunization with PSA-peptide induced specific T cell immunity in one-half of the patients with locally advanced and hormone-sensitive, metastatic CaP. DTH-derived T cells exhibited PSA-peptide-specific cytolytic activity and predominantly expressed a type-1 cytokine profile. SN - 0340-7004 UR - https://www.unboundmedicine.com/medline/citation/16283303/Induction_of_specific_T_cell_immunity_in_patients_with_prostate_cancer_by_vaccination_with_PSA146_154_peptide_ L2 - https://dx.doi.org/10.1007/s00262-005-0090-x DB - PRIME DP - Unbound Medicine ER -