Immunologic response to the dual murine anti-Id vaccine Melimmune-1 and Melimmune-2 in patients with high-risk melanoma without evidence of systemic disease.
Melimmune is a dual preparation of two murine anti-idiotypic antibodies (anti-Ids), Melimmune-1 and Melimmune-2, which mimic separate epitopes of the melanoma-associated high molecular weight proteoglycan antigen. In an animal model, vaccination with either anti-Id leads to tumor rejection, and Phase I clinical trials have demonstrated the tolerance of each reagent in humans. We conducted a Phase IB trial of different doses of a one-to-one composition to Melimmune-1 and Melimmune-2 administered with SAF-m adjuvant in patients with resected melanoma without evidence of metastatic disease. A total of 21 patients were enrolled in this multicenter trial. Detailed immune response analysis was conducted on 13 patients enrolled at a single institution. Following vaccination, 12 of the 13 patients demonstrated antibodies to both Melimmune-1 and Melimmune-2, including significant anti-V-region reactivity. Maximum anti-V-region reactivity was generally detected following the last vaccination. Anti-V-region reactivity directed at Melimmune-1 and Melimmune-2 in excess of 1 microgram/ml was detected in 4 and 10 of 12 patients, respectively. Sera from patients obtained at time of peak anti-V-region reactivity did not demonstrate the ability to inhibit Ab1 binding to tumor cells or direct anti-tumor cell reactivity. However, in vitro cellular proliferation was observed in response to Melimmune-1 and/or Melimmune-2 F(Ab')2 in all patients with a mean stimulation index of 12.0 and 27.8, respectively. Overall, the antibody and cellular immune response to Melimmune-2 was more potent than to Melimmune-1, and all antibody doses elicited an immune response. The optimal biologic dose of Melimmune could not be determined in this small patient population.
Saleh
M N
MN
University of Alabama, Birmingham 35294-3300, USA.
Lalisan
D Y
DY
Pride
M W
MW
Solinger
A
A
Mayo
M S
MS
LoBuglio
A F
AF
Murray
J L
JL
D000328:Adult; D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D016233:Immunotherapy, Active; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology; D011509:Proteoglycans / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D009363:Neoplasm Proteins; D011509:Proteoglycans; C069150:melanoma-associated proteoglycan antigen, human