Phase 1 trial of immunological adjuvant QS-21 with a GM2 ganglioside-keyhole limpet haemocyanin conjugate vaccine in patients with malignant melanoma.
Increasing doses of saponin fraction QS-21 were administered as immunological adjuvant in a Phase 1 trial with a constant dose of the melanoma ganglioside GM2 covalently attached to keyhole limpet haemocyanin (KLH). Twenty-eight patients with AJCC Stage III or IV melanoma who were free from disease after surgery were treated with six vaccinations administered subcutaneously over a 5-month period. Local and systemic reactions were QS-21 dose-related. Doses of < or = 100 micrograms induced mild local tenderness and inflammation at vaccination sites lasting 2-4 days and occasional brief low-grade fever and malaise, but no significant incapacitation. The 200 micrograms dose induced low-grade fever and malaise after 30% of vaccinations and local reactions as large as 20 cm in diameter were seen in all patients, resulting in discomfort with usage of the injected extremity for 5-10 days. The titres of IgM and IgG antibodies against GM2, and IgG antibodies against KLH, were highest at the 100 and 200 micrograms QS-21 doses. No antibodies against QS-21 were detected. This trial identifies the 100 micrograms dose of QS-21 as the optimal well tolerated dose for induction of antibodies against both the melanoma ganglioside/GM2 and the protein KLH in melanoma patients.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
P O
PO
Livingston
S
S
Adluri
F
F
Helling
T J
TJ
Yao
C R
CR
Kensil
M J
MJ
Newman
D
D
Marciani
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D005678:G(M2) Ganglioside / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008545:Melanoma / Q000628:therapy*; D012503:Saponins / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D012503:Saponins; D005678:G(M2) Ganglioside; C078785:saponin QA-21V1; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin