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Clinical Cancer Research Vol. 8, 967-972, May 2002
© 2002 American Association for Cancer Research

Advances in Brief

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 Adjuvants1

Susanne G. Schaed, Virginia M. Klimek, Katherine S. Panageas, Cristina M. Musselli, Leah Butterworth, Wen-Jen Hwu, Philip O. Livingston, Linda Williams, Jonathan J. Lewis, Alan N. Houghton and Paul B. Chapman2

Swim Across America Laboratory of Tumor Immunology [S. G. S., W-J. H., P. O. L., J. J. L., A. N. H., P. B. C.], and Departments of Medicine [V. M. K., C. M. M, L. B., W-J. H., P. O. L., L. W., J. J. L., A. N. H., P. B. C.], Surgery [J. J. L.], and Biostatistics and Epidemiology [K. S. P.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021

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 µg 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.




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Copyright © 2002 by the American Association for Cancer Research.