The site of binding of anti-CEA antibodies to tumour CEA in vivo: an immunocytochemical and autoradiographic approach

Moshakis, V.; Ormerod, M.G.; Westwood, J. H.; Imrie, S F; Neville, A. Munro

doi:10.1038/bjc.1982.159

Cited by 24 publications

(9 citation statements)

References 14 publications

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“…Autoradiographic techniques in s.c. tumors and lymph node metastases have also been carried out by several authors [25,30,31,33] as well as immunoperoxidase techniques [13,21]. Nearly all authors found preferential localization in the periphery of tumors which usually is the most vascular.…”

Section: Itemmentioning

confidence: 98%

The detection of virally induced tumors by 131I- and 125I-labeled syngeneic monoclonal antibodies

Berends

et al. 1988

Cancer Immunol Immunother

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The binding of the syngeneic monoclonal antibodies IC5F5 and 4D2B4 to Rauscher virus-induced myeloid leukemic (RMB-1) cells was analyzed in vivo in tumor-bearing BALB/c mice. To verify it these antibodies bind specifically to RMB-1 cells, purified antibodies were iodinated with the isotopes 125I and 131I. Mice previously inoculated with tumor cells were injected with these labeled monoclonal antibodies and the plasma clearance and the tissue distribution were determined. The clearance in tumor-bearing animals was faster than in control mice. The tissue distribution was corrected for nonspecific accumulation by scoring for an unrelated antibody. Calculation of a localization index showed that IC5F5 binds at least 4.5 times more specifically to tumor cells than to other tissues. A preferential localization of radioactivity in s.c. tumor tissue was seen in the scanning of animals injected with 131I-labeled antibodies. The most direct proof of specific binding was observed in autoradiograms of animals treated with 125I-labeled antibodies. Small islands of tumor cells in the livers of mice inoculated i.v. had a high density of grains compared to other tissues and also compared to tumor cells in mice treated with unrelated monoclonal antibodies. These results show efficient targeting of these monoclonal antibodies and make immunotherapy of these myeloid leukemic cells possible.

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Section: Itemmentioning

confidence: 98%

The detection of virally induced tumors by 131I- and 125I-labeled syngeneic monoclonal antibodies

Berends

et al. 1988

Cancer Immunol Immunother

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“…But, the fact that radiolabeled antibodies accumulate in the tumor site does not necessarily mean that the antibodies localize on the surface of tumor cells. Moshakis et al (1982) examined the site of binding of the injected anti-CEA antibody to the tumor CEA by a combination of immunocytochemistry and autoradiography and reported that the antibody was predominantly in extracellular spaces rich in CEA surrounding a xenografted human breast cancer in immunosuppressed mice. Kim et al (1980) considered that AFP producing tumors had an extracellular milieu of AFP which would provide a gradient between tumor and non-tumor adjacent tissues and this condition, thus, made radioimmunodetection possible, although AFP is a cytoplasmic tumor marker.…”

Section: Discussionmentioning

confidence: 99%

Relevance of anti-.ALPHA.-fetoprotein antibody for radioimmunodetection: Analysis with .ALPHA.-fetoprotein-secreting rat hepatoma and antigen-bound acrylic beads.

Tanno

Owada

Sato

et al. 1986

Tohoku J. Exp. Med.

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Using AFP-secreting AH66 rat hepatoma cells and AFP-bound acrylic beads (AFP-B), artificial cells expressing surface antigen, the effect of blood AFP level on the accumulation of radiolabeled rabbit anti-AFP antibody in the site of tumor and beads implanted in rats was examined. Scintigrams of hepatoma-bearing rats with implanted AFP-B showed a marked localization in AFP-B site, but not in the tumor site on day 5 after the injection of radiolabeled antibody. The imaging of AFP-B was most satisfactory in normal rats with extremely low blood AFP. Tissue/blood radioactivity ratio in AFP-B on day 5 was found to be significantly higher in normal rats (17.43±5.55), compared with 6.66+ 1.67 in the tumor-bearing rats (p <0.01), while the ratio of AFP-B in tumor-bearing rats remarkably recovered to 11.20+0.25 (p <0.01) after whole blood exchange to reduce an elevated serum AFP level. The accumulation of anti-AFP antibody in the tumor was not observed irrespective of AFP-B. Microautoradiography of tissue sections showed the specific localization of radioactivity on the surface of AFP-B but not on the surface or the inside of the tumor cells. Immune complexes were detected in plasma of tumor-bearing rats 1 min to 7 days after the administration of the radiolabeled antibody. In conclusion, the application of anti-AFP antibody for the diagnosis and treatment of tumors is limited to the case of the expression of AFP on the surface of tumor cells and lower AFP level in circulation.radioimmunodetection ; AFP ; anti-AFP antibody ; whole blood exchange

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“…In this respect, monoclonal antibodies (mAbs) recognizing tumour-associated antigens have been successfully applied as carriers of radionuclides [2], toxins [5] or cytostatic agents [14]. The antitumour effects appear to be limited because of the relatively low concentration of the cytotoxic reagent delivered to tumours [12].…”

Section: Introductionmentioning

confidence: 99%

Analysis of a conjugate between anti-carcinoembryonic antigen monoclonal antibody and alkaline phosphatase for specific activation of the prodrug etoposide phosphate

Haisma¹,

Boven²,

Muijen³

et al. 1992

Cancer Immunol Immunother

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The selective targeting of tumors by enzymes conjugated to monoclonal antibodies (mAb) may be an ideal approach to convert relatively nontoxic prodrugs into active agents at the tumour site. We used the anti-carcinoembryonic antigen mAb BW431/26 conjugated to alkaline phosphatase (AP) and phosphorylated etoposide (etoposide-P) as a prodrug to study the feasibility of this concept. Etoposide was phosphorylated with POCl3. Quantitative hydrolysis of etoposide-P to etoposide occurred within 10 min in the presence of AP. BW431/26 and AP were conjugated using a thioether bond. The AP conjugate retained 93% of its calculated activity. 125I-labelled AP conjugate did not show a reduction of immunoreactivity as determined by a cell-binding assay. SW1398 colon cancer cells were used to analyse the cytotoxicity of etoposide and etoposide-P. Etoposide (IC50 22 microM) was 100 times more toxic than etoposide-P (20% growth inhibition at 200 microM). Pretreatment of the cells with BW431/26-AP prior to etoposide-P exposure resulted in a dramatic increase in cytotoxicity (IC50 70 microM). The pharmacokinetics and tumour-localizing properties of BW431/27 and the AP conjugate were assessed in nude mice bearing SW1398 tumours. BW431/26 showed excellent tumour localization (10% of the injected dose/g tissue retained from 8 h to 120 h), whereas the AP conjugate showed a reduced tumour uptake (3%-0.3% of the injected dose/g tissue at 8-120 h), a faster clearance from the circulation and a high liver uptake. Radiolabelled AP showed a similar pharmacokinetic profile to the AP conjugate. Gel filtration analysis of blood, liver, and tumour samples indicated good stability of the conjugate.

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The site of binding of anti-CEA antibodies to tumour CEA in vivo: an immunocytochemical and autoradiographic approach

Cited by 24 publications

References 14 publications

The detection of virally induced tumors by 131I- and 125I-labeled syngeneic monoclonal antibodies

The detection of virally induced tumors by 131I- and 125I-labeled syngeneic monoclonal antibodies

Relevance of anti-.ALPHA.-fetoprotein antibody for radioimmunodetection: Analysis with .ALPHA.-fetoprotein-secreting rat hepatoma and antigen-bound acrylic beads.

Analysis of a conjugate between anti-carcinoembryonic antigen monoclonal antibody and alkaline phosphatase for specific activation of the prodrug etoposide phosphate

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