Original Article

Cancer Immunology, Immunotherapy

, Volume 54, Issue 3, pp 208-218

First online:

Phase I/II study of immunotherapy with T-cell peptide epitopes in patients with stage IV melanoma

  • Peter HerseyAffiliated withOncology and Immunology Unit Email author 
  • , Scott W. MenziesAffiliated withSydney Melanoma Unit, Royal Prince Alfred Hospital
  • , Brendon CoventryAffiliated withAdelaide Melanoma Unit, Department of Surgery, Royal Adelaide Hospital, University of Adelaide
  • , Tam NguyenAffiliated withOncology and Immunology Unit
  • , Margaret FarrellyAffiliated withOncology and Immunology Unit
  • , Susan CollinsAffiliated withNewcastle Melanoma Unit, Newcastle Mater Hospital
  • , Debbie HirstAffiliated withSydney Melanoma Unit, Royal Prince Alfred Hospital
  • , Heather JohnsonAffiliated withSydney Melanoma Unit, Royal Prince Alfred Hospital

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Previous studies in small groups of patients suggested that immunization of melanoma patients with peptide epitopes recognized by T cells could induce regression of melanoma. This approach was tested in 36 patients with stage IV melanoma. The (MHC class I–restricted) peptides were from gp100, MART-1, tyrosinase, and MAGE-3. The gp100 and MART-1 peptides had been modified to increase their immunogenicity. In half the patients (groups 3 and 4) the peptides were given in the adjuvant Montanide-ISA-720, and half the patients in both groups were given GM-CSF s.c. for 4 days following each injection. Treatment was well tolerated except for two severe erythematous responses to Montanide-ISA-720 and marked inflammatory responses at sites of GM-CSF administration in three patients. There were no objective clinical responses but stabilization of disease for periods from 3 to 12 months were seen in seven patients. Five of these were patients given the peptides in Montanide-ISA-720. Delayed-type hypersensitivity (DTH) skin test responses were also seen mainly in the patients given the peptides in Montanide-ISA-720. GM-CSF did not increase DTH responses in patients in the latter group but may have increased DTH responses in those not given peptides in Montanide-ISA-720. Inflammatory responses around s.c. metastases or regional lymph nodes were observed in two patients. These results suggest that the peptides are more effective when given in the adjuvant Montanide-ISA-720. Nevertheless, results from this study, together with those from a number of comparable studies, indicate that peptide vaccines are currently of minimal benefit to patients and support the need for ongoing development of new strategies in treatment of this disease.

Keywords

Adjuvants Clinical responses Melanoma Peptide vaccines T-cell responses