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High-affinity chimeric anti-(colorectal carcinoma) antibody correlated to enhanced tumor targeting in biodistribution and imaging

  • Original Papers
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

The genetically engineered chimeric cB72.3m4 and cB72.3m12 antibodies recognize the same tumor-associated TAG72 antigen. The high-affinity cB72.3m4 antibody had an approximately 18-fold higher affinity constant for the TAG72 antigen than the low-affinity cB72.3m12 antibody. The relationship between antibody affinity and tumor targeting was studied by using these two antibodies. In biodistribution and imaging studies in athymic mice bearing LS174T human colon cancer xenografts, the radiolabelled high-affinity cB72.3m4 antibody was rapidly cleared from the blood, whereas the low-affinity cB72.3m12 antibody had slower blood clearance. The data showed that the high-affinity cB72.3m4 antibody appeared to localize more in tumors (based on tumor:normal-tissue ratios) than did the low-affinity cB72.3m12 antibody, and enhanced the target-to-nontarget image contrast. This study provides evidence that the high-affinity chimeric antibody cB72.3m4 may be useful in both immunodetection and immunotherapy of cancer.

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Abbreviations

DMEM:

modified Eagle's medium

FCS:

fetal calf serum

PBS:

phosphate-buffered saline

BSA:

bovine serum albumin

SDS-PAGE:

sodium dodecyl sulfate/polyacrylamide gel electrophoresis

References

  • Carrasquillo J, Krohn K, Beaumier P, McGuffin R, Brown J, Hellstrom P, Larson S (1984) Diagnosis of and therapy for solid tumors and radiolabelled antibodies and immune fragments. Cancer Treat Rep 68:317–328

    Google Scholar 

  • Carrasquillo JA, Sugarbaker P, Colcher D, Reynolds JC, Esteban J, Bryant G, Keenan AM, Perentesis P, Yokoyanma K, Simpson DE, Ferroni P, Farkas R, Schlom J, Larson SM (1988) Radioimmunoscintigraphy of colon cancer with I-131-labeled B72.3 monoclonal antibody. J Nucl Med 29:1022–1030

    Google Scholar 

  • Chapman P, Lonberg M, Houghton A (1990) Light chain variants of an IgG3 anti-GD3 monoclonal antibody and the relationship among avidity, effector functions, tumor targeting, and anti-tumor activity. Cancer Res 50:1503–1509

    Google Scholar 

  • Colcher D, Esteban J, Carrasquillo J, Sugarbaker P, Larson S, Schlom J (1987 a) Quantitative analysis of selective radiolabelled monoclonal antibody localization in metastatic lesions of colorectal cancer patients. Cancer Res 47:1185–1189

    Google Scholar 

  • Colcher D, Esteban J, Carrasquillo J, Sugarbaker P, Larson S, Schlom J (1987 b) Complementation of intracavitary and intravenous administration of a monoclonal antibody B72.3 in patients with carcinoma. Cancer Res 47:4218–4224

    Google Scholar 

  • Colcher D, Minelli M, Roselli M, Muraro R, Simpson-Milenic D, Schlom J (1988) Radio immunolocalization of human carcinoma xenografts with B72.3 second generation monoclonal antibodies. Cancer Res 48:4597–4603

    Google Scholar 

  • Cope D, Dewhirst M, Friedman H, Bigner D, Zalutsky M (1990) Enhanced delivery of a monoclonal antibody F(ab)2 fragment to subcutaneous human glioma xenografts using local hyperthemia. Cancer Res 50:1803–1809

    Google Scholar 

  • DcNardo S, O'Grady L, Levy N, Mills S, Macey D, McGahan J, Miller C, Epstein A (1988) Pilot studies of radioimmunotherapy of B cell lymphoma and leukemia using 131I Lym-1 monoclonal antibody. Antibody Immunoconj Radiopharmacol 1:17–33

    Google Scholar 

  • Esteban JM, Colcher D, Sugarbaker P, Carrasquillo JA, Bryant G, Thor A, Reynolds JC, Larson SL, Schlom J (1987) Quantitative and qualitative aspects of radiolocalization in colon cancer patients of intravenously administered MAb B72.3. Int J Cancer 39:50–59

    Google Scholar 

  • Granowska M, Britton K, Shepherd J (1986) A prospective study of 125-I labelled monoclonal antibody imaging in ovarian cancer. J Clin Oncol 4:730–737

    Google Scholar 

  • Jain R (1990) Physiological barriers to delivery of monoclonal antibodies and other macromolecules in tumors. Cancer Res 50:814s-819s

    Google Scholar 

  • Kimura A, Xiang J (1986) High levels of Met 72 antigen expression: correlation with metastatic activity of B16 melanoma tumor cell variants. J Natl Cancer Inst 76:1247–1254

    Google Scholar 

  • Kjeldsen T, Clausen H, Hirohashi S, Ogawa T, Iijima H, Hakomori S (1988) Preparation and characterization of monoclonal antibodies to tumor-associated O-linked sialosyl-Tn epitope. Cancer Res 48:2214–2222

    Google Scholar 

  • Langmuir V, Mendonca H, Woo D (1992) Comparisons between two monoclonal antibodies that bind to the same antigen but have differing affinities: uptake kinetics and125I-antibody therapy efficacy in multicell spheroids. Cancer Res 52:4728–4734

    Google Scholar 

  • Lotze M, Carrasquillo J, Weinstein J (1986) Monoclonal antibody imaging of human melanoma: radioimmunodetection by subcutaneous or systemic injection. Ann Surg 204:19–31

    Google Scholar 

  • Mach J, Carrel S, Forni M, Ritschard J, Donath A, Alberto P (1980) Tumor localization of radiolabelled antibodies against carcinoembryonic antigen in patients with carcinoma. N Engl J Med 303:5–10

    Google Scholar 

  • Mach J, Chatal J, Lumbroso J (1984) Tumor localization in patients by radiolabelled monoclonal antibodies against colon carcinoma. Cancer Res 43:5593–5600

    Google Scholar 

  • Milenic D, Yokota T, Filpula D, Finkelman M, Dodd S, Wood J, Whitlow M, Snoy P, Schlom J (1991) Construction, binding properties, metabolism and tumor targeting of a single-chain Fv derived from the pancarcinoma monoclonal antibody CC49. Cancer Res 51:6363–6371

    Google Scholar 

  • Molinolo A, Simpson J, Thor A, Schlom J (1990) Enhanced tumor binding using immunohistochemical analyses by second generation anti-tumor-associated glycoprotein 72 monoclonal antibodies versus monoclonal antibody B72.3 in human tissue. Cancer Res 50:1291–1298

    Google Scholar 

  • Nuti M, Teramoto RA, Mariani-Costantini R, Hand P, Colcher D, Schlom J (1982) A monoclonal antibody (B72.3) defines patterns of distribution of a novel tumor-associated antigen in human mammary carcinoma cell populations. Int J Cancer 29:539–545

    Google Scholar 

  • Ohuchi N, Simpson JF, Colcher D, Schlom J (1987) Complementation of anti-CEA and anti-TAG-72 monoclonal antibodies in reactivity to human gastric-adenocarcinomas. Int J Cancer 40:726–733

    Google Scholar 

  • Order S, Klein J, Leichner P, Frincke J, Lollo C, Carlo D (1986)90Yitrium anti-ferritin: a new therapeutic radiolabelled antibody. J Radiat Oncol Biol Phys 12:227–281

    Google Scholar 

  • Renda A, Salvatore M, Sava M, Landi R, Lastoria S, Coppola L, Schlom J, Colcher D, Zannini G (1987) Immunoscintigraphy in the follow-up of patients operated on for carcinoma of the sigmoid and rectum. Preliminary report with a new monoclonal antibody B72.3. Dis Colon Rectum 30:683–686

    Google Scholar 

  • Schlom J, Eggensperger D, Colcher D, Molinolo A, Houchens D, Millers L, Hinkle G, Siler K (1992) Therapeutic advantage of high-affinity anticarcinoma radioimmunoconjugates. Cancer Res 52:1067–1072

    Google Scholar 

  • Sicke-Santanello BJ, P'Dwyer PJ, Mojzisik C, Tuttle SE, Hinkel GH, Rousseau M, Schlom J, Colcher D, Thurston MO, Nieroda C, Sardi A, Farrar WB, Mintom JP, Martin E (1987) Radioimmunoguided surgery using the monoclonal antibody B72.3 in colorectal tumors. Dis Colon Rectum 30:761–764

    Google Scholar 

  • Skockley T, Lin K, Sung C, Nagy J, Tompkins R, Dedrick R, Yarmush M (1992) A quantitative analysis of tumor specific monoclonal antibody uptake by human melanoma xenografts: effects of antibody immunological properties and tumor antigen expression levels. Cancer Res 52:357–366

    Google Scholar 

  • Stramingnoni D, Bowen R, Atkinson B, Schlom J (1983) Differential reactivity of monoclonal antibodies with human colon adenocarcinomas and adenomas. Int J Cancer 31:543–552

    Google Scholar 

  • Sung C, Shockley T, Morrison P, Dvorak H, Yarmush M, Dedrick R (1992) Predicted and observed effects of antibody affinity and antigen density on monoclonal antibody uptake in solid tumors. Cancer Res 52:377–384

    Google Scholar 

  • Thor A, Gorstein F, Ohuehi N, Szpak CA, Johnston WW, Schlom J (1986 a) Tumor-associated glycoprotein (TAG-72) in ovarian carcinomas defined by monoclonal antibody B72.3. J Natl Cancer Inst 76:995–1003

    Google Scholar 

  • Thor A, Ohuchi N, Szpak C, Johnston W, Schlom J (1986 b) Distribution of the oncofetal antigen, tumor associated glycoprotein-72 defined by the monoclonal antibody, B72.3. Cancer Res 46:3118–3124

    Google Scholar 

  • Xiang J, Chen Z (1992) Genetic engineering of high affinity anti-human colorectal tumor mouse/human chimeric antibody. Immunology 75:209–216

    Google Scholar 

  • Xiang J, Roder J, Hozumi N (1990) Production of murine V/human Cr1 chimeric anti-TAG72 antibody using V region cDNA amplified by PCR. Mol Immunol 27:809–817

    Google Scholar 

  • Xiang J, Delbaere L, Liu E, Chen Z (1993 a) The tyrosine residue at position 97 in the VH CDR3 region of an mouse/human chimeric anti-colorectal carcinoma antibody contributes hydrogen bonding to the TAG72 antigen. Cancer Biother (in press)

  • Xiang J, Moyana T, Chen Z, Skinnider L, Hamilton T (1993 b) High binding affinity chimeric anti-colorectal carcinoma antibody correlated to enhanced tumor binding and effector function. Cancer Biother (in press)

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Authors and Affiliations

  1. Saskatoon Cancer Center, Department of Microbiology and Division of Oncology, University of Saskatchewan, 20 Campus Drive, S7N 4H4, Saskatoon, Saskatchewan, Canada

    Yumin Qi & Jim Xiang

  2. Department of Nuclear Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    Gilbert Matte & Alex Wilkinson

Authors
  1. Yumin Qi
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  2. Gilbert Matte
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  3. Alex Wilkinson
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  4. Jim Xiang
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Additional information

This study is supported by research grants of the Medical Research Council of Canada and the Saskatchewan Cancer Foundation. Jim Xiang is a research scholar of MRC of Canada

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Qi, Y., Matte, G., Wilkinson, A. et al. High-affinity chimeric anti-(colorectal carcinoma) antibody correlated to enhanced tumor targeting in biodistribution and imaging. J Cancer Res Clin Oncol 120, 57–62 (1993). https://doi.org/10.1007/BF01200725

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  • DOI: https://doi.org/10.1007/BF01200725

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