T-cell responses against tyrosinase 368-376(370D) peptide in HLA*A0201+ melanoma patients: randomized trial comparing incomplete Freund's adjuvant, granulocyte macrophage colony-stimulating factor, and QS-21 as immunological adjuvants.
We conducted a randomized trial in HLA*A0201+ patientswith American Joint Committee on Cancer stage III or IV melanoma immunized with tyrosinase 368-376(370D) peptide and gp100 209-217(210M) peptide to compare the potency of three different adjuvants. Patients received 3 monthly immunizations with 500 microg of each peptide either with incomplete Freund's adjuvant (IFA), QS-21, or granulocyte macrophage colony-stimulating factor (GM-CSF). The primary end point was induction of IFN-gamma release by CD8+ T cells against tyrosinase and gp100 peptides measured by enzyme-linked immunospot assays without in vitro prestimulation measured pretreatment, 2 and 8 weeks after the third vaccination. Four of 9 and 4 of 8 patients immunized using QS-21 and GM-CSF, respectively, developed increased frequencies of CD8+ T cells against tyrosinase 370D peptide compared with 0 of 9 patients immunized using IFA (P = 0.045). T-cell responses against a gp100-related peptide showed similar results, but their relevance to T-cell reactivity against native gp100 209-217 is uncertain. These results show that: (a) QS-21 and GM-CSF are superior to IFA as immunological adjuvants for vaccination against tyrosinase 370D peptide; and (b) with appropriate adjuvants, increased frequencies of peptide-specific T cells after vaccination can be detected by enzyme-linked immunospot without prolonged prestimulation in vitro.
Schaed
Susanne G
SG
Swim Across America Laboratory of Tumor Immunology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Klimek
Virginia M
VM
Panageas
Katherine S
KS
Musselli
Cristina M
CM
Butterworth
Leah
L
Hwu
Wen-Jen
WJ
Livingston
Philip O
PO
Williams
Linda
L
Lewis
Jonathan J
JJ
Houghton
Alan N
AN
Chapman
Paul B
PB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology*; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D012503:Saponins / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination
D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D012503:Saponins; C078785:saponin QA-21V1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005620:Freund's Adjuvant; D014442:Monophenol Monooxygenase