Human dendritic cells, pulsed with either melanoma tumor cell lysates or the gp100 peptide(280-288), induce pairs of T-cell cultures with similar phenotype and lytic activity.
Dendritic cells (DCs) pulsed with unfractionated tumor cell lysates or defined tumor peptides provide potent vaccines which elicit strong antitumor immunity. In this study, we generated DCs from the 2-h adherent progenitor cells obtained from the peripheral blood of melanoma patients. These DCs were able to capture biotinylated melanoma tumor cell lysates. We examined the efficacy of immunogens composed of DCs loaded either with the melanoma peptide gp100 [amino acids 280-288 (DC/gp100)] or with lysates from melanoma tumor cells (DC/lysates) in inducing cytotoxic T-cells from autologous PBLs of HLA-A2 melanoma patients. After four to five weekly stimulations of bulk PBLs with DC/gp100 or DC/lysates, the cultures were enriched with CD3+ T-cells and exhibited one of three phenotypic and functional patterns: (1) Predominant expression of CD8+ and MHC class I-restricted CTLs which displayed strong lytic activity against melanoma cells and T2 cells loaded with the gp100 peptide, (2) mixed CD4+/CD8+ phenotype and weak lytic activity, or (3) nonlytic and predominantly CD4+ cultures. Interestingly, T-cell cultures from each patient exhibited similar phenotypes and lytic activities whether the stimulant was DC/gp100 or DC/cell lysates. Our study demonstrates that DCs pulsed with soluble melanoma peptides or cell lysates are capable of inducing CD8+ CTLs from autologous PBLs of some, but not all, melanoma patients. The function and phenotype of the generated T-cell cultures are governed by DCs since both antigens (the gp100 peptide and melanoma lysates), when presented by a given DC preparation, induced similar T-cell cultures. In summary, it may be difficult to predict the nature of the cellular responses elicited by DC/tumor antigen vaccines from patient to patient.
Abdel-Wahab
Z
Z
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
DeMatos
P
P
Hester
D
D
Dong
X D
XD
Seigler
H F
HF
D000951:Antigens, Neoplasm / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018929:Cell Culture Techniques; D002455:Cell Division; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008545:Melanoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010455:Peptides; D058951:gp100 Melanoma Antigen