98th Annual Meeting DOG 2000

V 407

Phase I trial of adjuvant vaccination with tyrosinase peptides and GM-CSF in high risk melanoma patients

F. Servetopoulou1, C. Scheibenbogen2, N. E. Bechrakis1, D. Schadendort3, A. SchmitteI2, E. Thiel2, U. Keilholz2, M. H. Foerster1

Introduction: Tumor cells express specific antigens that can be recognized by cytolytic T -lymphocytes(CTL's). After recognition, CTL's can Iyse autologous tumor cells. During the last years a number of tumor- associated and differentiation antigens have been identified; these antigens can be the target of a tumor orientated T- cell response. In this phase I study patients with ocular or cutaneous melanoma with a high risk for recurrence or development of metastatic disease were vaccinated in an adjuvant setting with peptide epitopes derived from the tumor differenciation antigen tyrosinase. Aims of the study were to evaluate the induction of specific T cells and toxicity.

Methods: Following surgery or irradiation, 21 patients with ocular and 16 patients with cutaneous melanoma received vaccinations of one to three tyrosinase peptides in a dose of 200 µg (day 0) together with different adjuvants: all patients received GM-CSF 75 µg from day -2 to +1, either alone (n=11), or together with tetanus toxoid 2 IE on day 0 (n=10), or KLH (VacmunR) 0,4 mg on day 0 (n=8), or Interleukin-4 100 mg from day -2 to +1 (n=8). Vaccination cycles were repeated at weeks 2, 4, 6, 10 and 14. The induction of peptide-specific CD8+ T-cells was determined with an IFN?- ELISPOT assay directly from peripheral blood cells.

Results: 37 patients have been enrolled and the main toxicity observed was grade 1 and 2 swelling and inflammation at the site of injection. 17 patients have completed the 6 cycles of vaccination and are therefore evaluable for T -cell response. In 6 out of 11 receiving GM-CSF as adjuvant and in 6 out of 6 patients receiving GM-CSF and tetanus toxoid, tyrosinase- specific T -cells could be generated.

Discussion: These results show that in ocular and cutaneous melanoma vaccination with tyrosinase plus GM-CSF is able to induce a specific T -cell response in an adjuvant setting and preliminary data suggest that addition of tetanus toxoid as adjuvant increases immunogenicity.

1Augenklinik, Klinikum Benjamin Franklin, Freie Universität Berlin; 2Medizinische Klinik Hämatologie, Onkologie, UKBF Berlin; 3Klinische Kooperationseinheit für Dermatoonkologie, DKFZ, Klinikum Mannheim