Localization of GD2-specific Monoclonal Antibody 3F8 in Human Osteosarcoma

John P. Heiner, Floro Miraldi, Steven Kallick, John Makley, John Neely, William H. Smith-Mensah, Nai Kong V. Cheung

Research output: Contribution to journalArticle

Abstract

3F8 is a murine IgG3 monoclonal antibody specific for the antigen disialoganglioside GD2- Immimofluorescence staining showed strong binding of 3F8 to 15 of 17 human osteosarcomas, including primary and metastatic tumors. The targeting potentials of the native monoclonal antibody (3F8) and the F(ab')2 fragment (p-3F8) were tested in BALB/c athymic nude mice xenografted with human osteosarcomas. After radio-labeling with iodine using the chloramine T method, both 3F8 and p-3F8 retained immunoreactivities. The irrelevant IgG3 antibody TIBI14 and its F(ab')2 fragment were used as negative controls. A Ewing's sarcoma xenograft, which was low in gd2 antigen, was also studied for comparison. Mice were sacrificed 1 day and 4 days after i.v. antibody injection. 3F8 and p-3F8 showed preferential accumulation in osteosarcoma over normal tissues with tumonnontumor ratios of 2.7-58:1 and 1.4-82:1, respectively, on Day 1. These ratios improved to 10-163:1 and 6.0-75:1 on Day 4. The intact antibody 3F8 showed selective tumor uptake with a much higher percentage of iqjected dose per g than the fragment p-3F8 and exhibited a longer tissue half-life than p-3F8. These data indicate that anti-GD2 monoclonal antibodies may be useful for imaging and targeted therapy of human osteogenic sarcoma. The F(ab')2 fragment has the advantage of achieving favorable tumonnontumor ratios sooner after antibody injection while the intact antibody shows better retention by tumor tissues.

Original languageEnglish (US)
Pages (from-to)5401-5406
Number of pages6
JournalCancer Research
Volume47
Issue number20
StatePublished - Jan 1 1987

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Osteosarcoma
Monoclonal Antibodies
Antibodies
Nude Mice
Immunoglobulin G
Antigens
Neoplasms
Injections
Ewing's Sarcoma
Radio
Heterografts
Iodine
Half-Life
Staining and Labeling
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Heiner, J. P., Miraldi, F., Kallick, S., Makley, J., Neely, J., Smith-Mensah, W. H., & Cheung, N. K. V. (1987). Localization of GD2-specific Monoclonal Antibody 3F8 in Human Osteosarcoma. Cancer Research, 47(20), 5401-5406.
Heiner, John P. ; Miraldi, Floro ; Kallick, Steven ; Makley, John ; Neely, John ; Smith-Mensah, William H. ; Cheung, Nai Kong V. / Localization of GD2-specific Monoclonal Antibody 3F8 in Human Osteosarcoma. In: Cancer Research. 1987 ; Vol. 47, No. 20. pp. 5401-5406.
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Heiner, JP, Miraldi, F, Kallick, S, Makley, J, Neely, J, Smith-Mensah, WH & Cheung, NKV 1987, 'Localization of GD2-specific Monoclonal Antibody 3F8 in Human Osteosarcoma', Cancer Research, vol. 47, no. 20, pp. 5401-5406.

Localization of GD2-specific Monoclonal Antibody 3F8 in Human Osteosarcoma. / Heiner, John P.; Miraldi, Floro; Kallick, Steven; Makley, John; Neely, John; Smith-Mensah, William H.; Cheung, Nai Kong V.

In: Cancer Research, Vol. 47, No. 20, 01.01.1987, p. 5401-5406.

Research output: Contribution to journalArticle

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T1 - Localization of GD2-specific Monoclonal Antibody 3F8 in Human Osteosarcoma

AU - Heiner, John P.

AU - Miraldi, Floro

AU - Kallick, Steven

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AU - Neely, John

AU - Smith-Mensah, William H.

AU - Cheung, Nai Kong V.

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Y1 - 1987/1/1

N2 - 3F8 is a murine IgG3 monoclonal antibody specific for the antigen disialoganglioside GD2- Immimofluorescence staining showed strong binding of 3F8 to 15 of 17 human osteosarcomas, including primary and metastatic tumors. The targeting potentials of the native monoclonal antibody (3F8) and the F(ab')2 fragment (p-3F8) were tested in BALB/c athymic nude mice xenografted with human osteosarcomas. After radio-labeling with iodine using the chloramine T method, both 3F8 and p-3F8 retained immunoreactivities. The irrelevant IgG3 antibody TIBI14 and its F(ab')2 fragment were used as negative controls. A Ewing's sarcoma xenograft, which was low in gd2 antigen, was also studied for comparison. Mice were sacrificed 1 day and 4 days after i.v. antibody injection. 3F8 and p-3F8 showed preferential accumulation in osteosarcoma over normal tissues with tumonnontumor ratios of 2.7-58:1 and 1.4-82:1, respectively, on Day 1. These ratios improved to 10-163:1 and 6.0-75:1 on Day 4. The intact antibody 3F8 showed selective tumor uptake with a much higher percentage of iqjected dose per g than the fragment p-3F8 and exhibited a longer tissue half-life than p-3F8. These data indicate that anti-GD2 monoclonal antibodies may be useful for imaging and targeted therapy of human osteogenic sarcoma. The F(ab')2 fragment has the advantage of achieving favorable tumonnontumor ratios sooner after antibody injection while the intact antibody shows better retention by tumor tissues.

AB - 3F8 is a murine IgG3 monoclonal antibody specific for the antigen disialoganglioside GD2- Immimofluorescence staining showed strong binding of 3F8 to 15 of 17 human osteosarcomas, including primary and metastatic tumors. The targeting potentials of the native monoclonal antibody (3F8) and the F(ab')2 fragment (p-3F8) were tested in BALB/c athymic nude mice xenografted with human osteosarcomas. After radio-labeling with iodine using the chloramine T method, both 3F8 and p-3F8 retained immunoreactivities. The irrelevant IgG3 antibody TIBI14 and its F(ab')2 fragment were used as negative controls. A Ewing's sarcoma xenograft, which was low in gd2 antigen, was also studied for comparison. Mice were sacrificed 1 day and 4 days after i.v. antibody injection. 3F8 and p-3F8 showed preferential accumulation in osteosarcoma over normal tissues with tumonnontumor ratios of 2.7-58:1 and 1.4-82:1, respectively, on Day 1. These ratios improved to 10-163:1 and 6.0-75:1 on Day 4. The intact antibody 3F8 showed selective tumor uptake with a much higher percentage of iqjected dose per g than the fragment p-3F8 and exhibited a longer tissue half-life than p-3F8. These data indicate that anti-GD2 monoclonal antibodies may be useful for imaging and targeted therapy of human osteogenic sarcoma. The F(ab')2 fragment has the advantage of achieving favorable tumonnontumor ratios sooner after antibody injection while the intact antibody shows better retention by tumor tissues.

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Heiner JP, Miraldi F, Kallick S, Makley J, Neely J, Smith-Mensah WH et al. Localization of GD2-specific Monoclonal Antibody 3F8 in Human Osteosarcoma. Cancer Research. 1987 Jan 1;47(20):5401-5406.