Report of immune monitoring of prostate cancer patients undergoing T-cell therapy using dendritic cells pulsed with HLA-A2-specific peptides from prostate-specific membrane antigen (PSMA).
BACKGROUND
In this paper we describe our program for the immune monitoring of phase II participants given dendritic cell (DC)/prostate-specific membrane antigen (PSMA)-based immunotherapy, and we also present some initial findings.


METHODS
Phase II subjects received six administrations of autologous dendritic cells exogenously pulsed with two peptides derived from PSMA. Prior to the initial infusion, and following each treatment, peripheral blood mononuclear cells (PBMC) were collected for the generation of dendritic cells as well as for comprehensive immune monitoring.


RESULTS
Thus far, an increase in PSMA-peptide-specific as well as overall cellular reactivity has been observed in several patients receiving DC plus PSM-P1 and -P2, as measured by delayed-type hypersensitivity (DTH) test and enzyme-linked immunosorbant assay (ELISA).


CONCLUSIONS
Our initial observations using an ELISA and DTH test indicate that we are enhancing cellular immunity in prostate cancer patients following infusion with DC plus PSMA-derived peptides. Several methods are underway to comprehensively monitor both cell-mediated and humoral immune responsiveness, including: determining anti-PSMA serum antibody titers, testing immunogen-restricted responder-cell proliferation and cytotoxicity, assessing aberrations in signal transduction, antigen processing, and presentation, and measuring soluble factors that may promote tumor outgrowth.
Salgaller
M L
ML
Northwest Biotherapeutics, L.L.C., Pacific Northwest Cancer Foundation, Seattle, Washington 98125, USA. mls@nwbio.org
Lodge
P A
PA
McLean
J G
JG
Tjoa
B A
BA
Loftus
D J
DJ
Ragde
H
H
Kenny
G M
GM
Rogers
M
M
Boynton
A L
AL
Murphy
G P
GP
D000951:Antigens, Neoplasm / Q000276:immunology*; D000954:Antigens, Surface; D002268:Carboxypeptidases / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005805:Genes, MHC Class I; D043425:Glutamate Carboxypeptidase II; D015234:HLA-A Antigens / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015234:HLA-A Antigens; D002268:Carboxypeptidases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II