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
| Autor: | Michael W. Pride, James L. Murray, Albert F. LoBuglio, Mansoor N. Saleh, Alan Solinger, D. Y. Lalisan, Matthew S. Mayo |
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| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Cancer Research Systemic disease Antibodies Neoplasm Immunology Lymphocyte Activation Cancer Vaccines Epitope Epitopes Mice Immune system Antigen Antigens Neoplasm medicine Immunology and Allergy Animals Humans Melanoma Aged Pharmacology Immunity Cellular biology business.industry Immunotherapy Active Middle Aged medicine.disease Vaccine therapy Antibodies Anti-Idiotypic Neoplasm Proteins Vaccination biology.protein Female Proteoglycans Antibody business |
| Zdroj: | Journal of immunotherapy (Hagerstown, Md. : 1997). 21(5) |
| ISSN: | 1524-9557 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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