Vaccination of patients with small-cell lung cancer with synthetic fucosyl GM-1 conjugated to keyhole limpet hemocyanin Journal Article
| Authors: | Krug, L. M.; Ragupathi, G.; Hood, C.; Kris, M. G.; Miller, V. A.; Allen, J. R.; Keding, S. J.; Danishefsky, S. J.; Gomez, J.; Tyson, L.; Pizzo, B.; Baez, V.; Livingston, P. O. |
| Article Title: | Vaccination of patients with small-cell lung cancer with synthetic fucosyl GM-1 conjugated to keyhole limpet hemocyanin |
| Abstract: | Purpose: Immunotherapy directed toward cell surface antigens may provide a novel approach to the eradication of chemoresistant micrometastatic disease in patients with small-cell lung cancer (SCLC). Studies in SCLC cell lines and human tissues suggest that the ganglioside fucosyl GM1 is an abundant yet specific target. A prior clinical study demonstrated the potent immunogenicity of fucosyl GM-1 derived from bovine thyroid gland, conjugated to keyhole limpet hemocyanin (KLH) and administered with QS-21 adjuvant. Experimental Design: We tested the immunogenicity of three different doses of a synthetic version of fucosyl-GM1 in patients with SCLC after a major response to initial therapy. The primary end point was to establish the lowest effective dose capable of inducing antibody production. Results: Five of six patients at the 30-μg dose and three of five patients at the 10-μg dose mounted IgM responses of 1:80 or greater. These antibodies were confirmed by flow cytometry in seven of eight cases. None of the patients at the 3-μg dose had titers above 1:80. One patient at the 30-μg dose had an IgG response with a titer of 1:80. The sera from six of the eight responders induced potent complement-mediated cytotoxicity of tumor cells. Conclusions: Vaccination with the synthetic fucosyl GM1-KLH conjugate induces an IgM antibody response against fucosyl GM1 and tumor cells expressing fucosyl GM1, comparable with the response induced by the bovine derivative. We plan to combine synthetic fucosyl GM1 vaccine at a dose of 30 μg with vaccines against three other antigens-GM2, Globo H, and polysialic acid-to test in patients with SCLC after initial chemotherapy. |
| Keywords: | adult; clinical article; aged; aged, 80 and over; middle aged; unclassified drug; cancer patient; flow cytometry; animals; lung neoplasms; time factors; lung small cell cancer; membrane antigen; immune tolerance; molecular sequence data; immunotherapy; immunoglobulin g; cancer vaccines; immunogenicity; antibody response; vaccination; polysialic acid; cattle; ganglioside gm1; enzyme-linked immunosorbent assay; cell separation; antibodies, neoplasm; models, chemical; carbohydrate sequence; antibody production; antibody titer; complement dependent cytotoxicity; fucosylganglioside gm1; keyhole limpet hemocyanin; hemocyanin; immunoglobulin m; carcinoma, small cell; conjugation; qs 21; adjuvant; synthetic peptide; eradication therapy; chromatography, thin layer; complement system proteins; g(m1) ganglioside; humans; human; male; female; priority journal; article; fucosylation |
| Journal Title: | Clinical Cancer Research |
| Volume: | 10 |
| Issue: | 18 Part 1 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2004-09-15 |
| Start Page: | 6094 |
| End Page: | 6100 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-04-0482 |
| PROVIDER: | scopus |
| PUBMED: | 15447995 |
| DOI/URL: | |
| Notes: | Clin. Cancer Res. -- Cited By (since 1996):71 -- Export Date: 16 June 2014 -- CODEN: CCREF -- Source: Scopus |
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