Recovery of zeta-chain expression and changes in spontaneous IL-10 production after PSA-based vaccines in patients with prostate cancer.
Circulating T lymphocytes of patients with prostate cancer have been reported to have functional deficits, including low or absent zeta-chain expression. To determine whether these functional impairments could be reversed by prostate specific antigen-based vaccination therapy, 10 patients treated with recombinant human prostate specific antigen plus GM-CSF and eight others receiving prostate specific antigen plus oil emulsion in two pilot clinical trials were evaluated prior to and after vaccination for several immunologic end points, including zeta-chain expression and cytokine production by circulating T cells as well as the frequency of T cells able to respond to prostate specific antigen in ELISPOT assays. The flow cytometry assay for zeta-chain expression was standardized to allow for a reliable comparison of pre- vs post-vaccination samples. Prior to therapy, the patients were found to have significantly lower zeta-chain expression in circulating CD3(+) cells and a higher percentage of zeta-chain negative CD3(+) and CD4(+) cells than normal donors. The patients' peripheral blood mononuclear cells spontaneously produced more IL-10 ex vivo than those of normal controls. After vaccination, recovery of zeta-chain expression was observed in 50% of patients in both clinical trials. Also, spontaneous IL-10 secretion by peripheral blood mononuclear cells decreased following immunotherapy in patients treated with prostate specific antigen and GM-CSF. The frequency of prostate specific antigen-reactive T cells was detectable in 7 out of 18 patients vs 4 out of 18 patients prior to vaccination. Only one of 18 patients was a clinical responder. The vaccine had stimulatory effects on the patients' immune system, but post-vaccine immune recovery could not be correlated to progression-free survival in this small cohort of patients with prostate cancer.
Meidenbauer
N
N
University of Pittsburgh Cancer Institute, W1041 Biomedical Science Tower, 211 Lothrop Street, Pittsburgh, Pennsylvania, PA 15213-2582, USA.
Gooding
W
W
Spitler
L
L
Harris
D
D
Whiteside
T L
TL
D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology*; D002277:Carcinoma / Q000188:drug therapy / Q000276:immunology*; D018572:Disease-Free Survival; D005434:Flow Cytometry; D005914:Globins / Q000096:biosynthesis*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000276:immunology* / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
D019496:Cancer Vaccines; D016753:Interleukin-10; D005914:Globins; D017430:Prostate-Specific Antigen