Localization of an anti-CEA monoclonal antibody in colo-rectal carcinoma xenografts

Pimm, M. V.; Armitage, N. C.; Perkins, Alan C.; Smith, William K.; Baldwin, Robert

doi:10.1007/bf00199305

Cited by 23 publications

(11 citation statements)

References 17 publications

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“…by immunoperoxidase staining or by in vitro application of radiolabeled antibody to tumor sections. Our results confirm and extend those of Moshakis et al [18] and Pimm et al [19].…”

Section: Discussionsupporting

confidence: 95%

Autoradiographic analysis of monoclonal antibody distribution in human colon and breast tumor xenografts

Jones

Gallagher

Sands

1986

Cancer Immunol Immunother

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The targeting of monoclonal antibodies to human tumor xenografts in nude mice was investigated by analysis of the cellular distribution of two radioiodinated monoclonal antibodies, B6.2 and B72.3, which recognize different tumor-associated antigens. The time course of distribution of each antibody within Clouser human mammary carcinoma (B6.2 positive, B72.3 negative) and LS174T human colorectal carcinoma (B6.2 positive, B72.3 positive) following i.v. injections was compared using autoradiographic techniques, which were also used to determine the pattern of binding after in vitro incubation with radiolabeled antibody. Both in vivo and in vitro localization of 125I-B72.3 in LS174T were characterized by the binding of antibody to antigen-rich mucin globules. In contrast, in vivo localization of B6.2 was restricted to groups of cells in well vascularized regions. Thus, the in vivo accumulations of B6.2 and B72.3 although quantitatively similar showed very different spatial distributions within LS174T tumors. The in vivo binding of B6.2 in Clouser tumors was restricted to small clusters of cells scattered fairly evenly throughout the tumor. There was no evidence for the presence of such antigen-rich foci after in vitro incubation of tumor sections with B6.2 suggesting that heterogeneity of regional uptake may be due to differences in antibody delivery. This type of information may provide a rational basis for the selection of appropriate therapeutic isotopes for radioimmunotherapy studies using these and other tumor models.

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“…by immunoperoxidase staining or by in vitro application of radiolabeled antibody to tumor sections. Our results confirm and extend those of Moshakis et al [18] and Pimm et al [19].…”

Section: Discussionsupporting

confidence: 95%

Autoradiographic analysis of monoclonal antibody distribution in human colon and breast tumor xenografts

Jones

Gallagher

Sands

1986

Cancer Immunol Immunother

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“…However the correlation would have been better if it were not for a tendancy for the localised antibody to fall slightly over this period. With these data the correlation (r --0.85) between tumour weight and counts localised from 1 to 8 days, was similar to that reported [14] for another anti-CEA antibody administered in moderate doses. At the 256 p~g dose, however, the less good correlation (r = 0.41) is more likely to have been due to differences in antibody clearance since, at the 256 Izg dose, antibody concentration in the tumour remained fairly constant (4.5% + 0.7% up to 8 days).…”

Section: Discussionsupporting

confidence: 82%

Effect of dose escalation of a monoclonal anti-CEA IgG on tumour localisation and tissue distribution in nude mice xenografted with human colon carcinoma

Boden

et al. 1986

Cancer Immunol Immunother

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A monoclonal anti-CEA antibody (1H12) has been examined for the effect of dosage on tumour localisation in immunodeprived mice xenografted with human colon carcinoma. Increased doses produced a linear rise in the absolute concentration found in the tumour but this was found to depend on tumour size, with the smaller tumours (mean weight 44 mg) accumulating significantly more antibody compared to larger tumours (mean weight 146 mg). With the smallest tumour (18 mg), in which saturation was achieved, a 500 micrograms dose produced a concentration in tumour of 60 micrograms/g. In the larger tumours a dose of 256 micrograms produced a mean concentration of 5.2 micrograms/g. Prolonged retention of 1H12 by tumour up to 8 days, observed at doses of 4, 128 and 256 micrograms, indicated that the dynamics of localisation is unaffected by dosage. Increased doses of 125I-1H12 caused an increase in the levels of radioactivity associated with all normal tissues studied. Thus at 8 days after injection an increase from 4 to 128 micrograms produced 50% and 42% declines in the tumour to blood and liver ratios, respectively. Cumulative localisation of 1H12 in tumour, from 4 h to 8 days, relative to normal tissue clearance was diminished on increasing dosage. This study shows that attempted therapy with escalated amounts of intact antibody is likely to be limited by a protracted excretory process and measures aimed at accelerating circulatory clearance are necessary.

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“…Numerous investigators used monoclonal antibodies developed against human tumor cells to radioimage tumor xenografts, usually in nude mouse model systems (2)(3)(4)(5)(6)(7)(8)(9). However, most of these studies focused on poorly defined and often nonspecific tumor-associated antigens.…”

mentioning

confidence: 99%

Human parathyroid antigen: characterization and localization with monoclonal antibodies.

Cance¹,

Wells²,

Dilley³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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A cell surface antigen on human parathyroid cells was identified by monoclonal antibodies. The antigen, called parathyroid antigen (PTA), is found on both of two major polypeptides (190 kDa and 160 kDa) apparently associated exclusively with parathyroid cells. To determine whether PTA was a suitable target for in vivo imaging, 125I-labeled anti-PTA was injected into nude mice bearing human parathyroid xenografts. IgG1 anti-PTA antibody showed excellent radiolocalization of the grafts, whereas IgM anti-PTA, containing the same variable domains as the IgG1 antibody, showed little specific binding. These results suggest that antibody isotype is an important parameter for the in vivo immunoscintigraphy of specific cellular antigens.

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Localization of an anti-CEA monoclonal antibody in colo-rectal carcinoma xenografts

Cited by 23 publications

References 17 publications

Autoradiographic analysis of monoclonal antibody distribution in human colon and breast tumor xenografts

Autoradiographic analysis of monoclonal antibody distribution in human colon and breast tumor xenografts

Effect of dose escalation of a monoclonal anti-CEA IgG on tumour localisation and tissue distribution in nude mice xenografted with human colon carcinoma

Human parathyroid antigen: characterization and localization with monoclonal antibodies.

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