Immunization of mice with fucosyl-GM1 conjugated with keyhole limpet hemocyanin results in antibodies against human small-cell lung cancer cells Journal Article
| Authors: | Cappello, S.; Liu, N. X.; Musselli, C.; Brezicka, F. T.; Livingston, P. O.; Ragupathi, G. |
| Article Title: | Immunization of mice with fucosyl-GM1 conjugated with keyhole limpet hemocyanin results in antibodies against human small-cell lung cancer cells |
| Abstract: | Fucosyl-GM1 (Fuc-GM1)[Fucα1 → 2Ga1β1 → 3GalNAcβ1 → 4(NeuAcα2- 3)Galβ1 → 4Glcβ1 → O-Cer] is a small-cell-lung-cancer (SCLC)-associated ganglioside initially defined by the murine monoclonal antibody F12. On the basis of its known distribution, Fuc-GM1 is a potential target for active immunotherapy in SCLC patients. Fuc-GM1 has been extracted and purified from bovine thyroid. The immunogenicity of Fuc-GM1 was tested in mice either alone, mixed with carrier protein keyhole limpet hemocyanin (KLH) or covalently linked with KLH, plus immunological adjuvant QS-21. The Fuc-GM1- KLH conjugate plus QS-21 adjuvant was found to be optimal. It induced consistent IgM and IgG enzyme-linked immunosorbent assay (ELISA) titers against Fuc-GM1. These antibodies were strongly reactive with the strongly Fuc-GM1-positive rat hepatoma cell line H4-II-E, and they were moderately reactive with the moderately positive human SCLC cell line H146 by flow cytometry and complement-mediated lysis. Both ELISA and fluorescence- activated cell sorting (FACS) reactions were inhibited with Fuc-GM1 or H4-II- E but not with the structurally related ganglioside GM1 or Fuc-GM1-negative colon cancer cell line LS-C. On the basis of these results, a vaccine comprising Fuc-GM1-KLH plus QS-21 is being prepared for testing in patients with SCLC. |
| Keywords: | human cell; nonhuman; flow cytometry; animal cell; mouse; animals; mice; cancer immunotherapy; lung neoplasms; colonic neoplasms; tumor cells, cultured; enzyme linked immunosorbent assay; lung small cell cancer; immunotherapy; cancer vaccine; cancer vaccines; immunogenicity; cancer immunization; rat; organ specificity; cytotoxicity, immunologic; cattle; rats; enzyme-linked immunosorbent assay; adjuvants, immunologic; antibodies, neoplasm; carbohydrate analysis; cell selection; saponins; carcinoma, small cell; immunization; gangliosides; ganglioside; sclc; liver neoplasms, experimental; complement system proteins; g(m1) ganglioside; humans; human; female; priority journal; article; immunogen; fucosyl-gm1 |
| Journal Title: | Cancer Immunology, Immunotherapy |
| Volume: | 48 |
| Issue: | 9 |
| ISSN: | 0340-7004 |
| Publisher: | Springer |
| Date Published: | 1999-11-01 |
| Start Page: | 483 |
| End Page: | 492 |
| Language: | English |
| PUBMED: | 10602885 |
| PROVIDER: | scopus |
| DOI: | 10.1007/s002620050596 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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16Musselli -
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228Livingston -
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