Immunization using autologous dendritic cells pulsed with the melanoma-associated antigen gp100-derived G280-9V peptide elicits CD8+ immunity.
OBJECTIVE
To determine the toxicity, maximal tolerated dose, and clinical and immunologic response to autologous dendritic cells pulsed with melanoma-associated antigen gp100-derived G280-9V peptide.


METHODS
Twelve HLA-A*0201(+) patients with advanced melanoma were administered dendritic cells pulsed with G280-9V peptide. Cohorts of three patients were administered 5 x 10(6), 15 x 10(6), and 50 x 10(6) cells i.v. every 3 weeks for six doses according to a dose escalation scheme. Three additional patients were treated at the highest dose. No additional cytokines or therapies were coadministered. The immunogenicity of G280-9V-pulsed dendritic cells was measured by IFN-gamma ELISPOT assay, tetramer assay, and (51)Cr release assay comparing prevaccination to postvaccination blood samples. Response to treatment was assessed by Response Evaluation Criteria in Solid Tumors.


RESULTS
CD8(+) immunity to the native G280 was observed in 8 (67%) patients as measured by ELISPOT and in 12 (100%) patients as measured by tetramer assay. Of the 9 patients tested, 9 (100%) had measurable high-avidity CTL activity as defined by lysis of allogeneic melanoma lines, which coexpress HLA-A*0201 and gp100. The median follow-up of the entire cohort is 43.8 months. Two (17%) partial responses were observed and 3 (25%) patients had stable disease. The median survival of the treated population was 37.6 months. At this time, three patients are alive, including one patient who continues to respond without additional treatment.


CONCLUSIONS
The high rate of immunization as measured by three independent assays and the occurrence of clinical regression support continued investigation of G280-9V peptide as a candidate epitope in melanoma vaccine formulations.
Linette
Gerald P
GP
Division of Hematology-Oncology, Department of Medicine, Massachusetts General Hospital, Boston, 02114, USA.
Zhang
Dongsheng
D
Hodi
F Stephen
FS
Jonasch
Eric P
EP
Longerich
Simonne
S
Stowell
Christopher P
CP
Webb
Iain J
IJ
Daley
Heather
H
Soiffer
Robert J
RJ
Cheung
Amy M
AM
Eapen
Sara G
SG
Fee
Sharon V
SV
Rubin
Krista M
KM
Sober
Arthur J
AJ
Haluska
Frank G
FG
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019496:Cancer Vaccines; D002469:Cell Separation; D015331:Cohort Studies; D003713:Dendritic Cells / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015234:HLA-A Antigens / Q000096:biosynthesis; D015789:HLA-A2 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000401:mortality / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome; D058951:gp100 Melanoma Antigen
D019496:Cancer Vaccines; C548640:G280-9V peptide; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D010455:Peptides; D058951:gp100 Melanoma Antigen; D007371:Interferon-gamma