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. 1996 Apr;87(4):405–411. doi: 10.1111/j.1349-7006.1996.tb00237.x

A Human/Mouse Chimeric Monoclonal Antibody against Intercellular Adhesion Molecule‐1 for Tumor Radioimmunoimaging

Miyuki Yamamura 1, Yuji Hinoda 1,✉, Shigeru Sasaki 1, Masayuki Tsujisaki 1, Noboru Oriuchi 2, Keigo Endo 2, Kohzoh Imai 1
PMCID: PMC5921110  PMID: 8641973

Abstract

A mouse‐human chimeric antibody for intercellular adhesion molecule‐1 (ICAM‐1) was established by using heavy chain loss mouse mutant hybridoma and human immunoglobulin expression vector. The HA58 hybridoma secreted anti‐ICAM‐1 monoclonal antibody (MoAb) (IgG1, k). The gene of the mouse variable region of heavy chain was amplified and cloned by the polymerase chain reaction technique directly from the HA58 hybridoma RNA. The variable region of heavy chain was joined with an expression vector which contains human γ1 constant gene. The expression vector was transfected into heavy chain loss mutant cells HA58‐7, which produced only murine immunoglobulin light chains. The resultant chimeric MoAb HA58, chHA58, retained full‐binding reactivity to ICAM‐1 compared with murine HA58 parental antibody. The chimeric MoAb chHA58 showed little antibody dependent cell‐mediated cytotoxic activity against cultured tumor cells. Biodistribution studies with 99mTc‐labeled chHA58 in nude mice bearing human gastric carcinoma JRST cells demonstrated that the tumor‐blood ratio was 1.55 at 18 h after injection, when the tumors were clearly visible in gamma scintigraphy. These data suggest that chHA58 may be of practical use for radioimmunoimaging of a wide variety of tumors.

Keywords: Chimeric monoclonal antibody, ICAM‐1, Radioimmunoimaging

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REFERENCES

  • 1. ) Rothlein , R. , Dustin , M. L. , Marlin , S. D. and Springer , T. A.A human intercellular adhesion molecule‐1 (ICAM‐1) distinct from LFA‐1 . J. Immunol. , 137 , 1270 – 1274 ( 1986. ). [PubMed] [Google Scholar]
  • 2. ) Diamond , M. S. , Staunton , D. E. , Marlin , S. D. and Springer , T. A.Binding of the integrin Mac‐1 (CD11b/CD18) to the third immunoglobulin‐like domain of ICAM‐1 (CD54) and its regulation by glycosylation . Cell , 65 , 961 – 971 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Rosenstein , Y. , Park , J. K. , Hahn , W. C. , Rosen , F. S. , Bierer , B. E. and Burakoff , S. J.CD43, a molecule defective in Wiskott‐Aldrich syndrome, binds ICAM‐1 . Nature , 354 , 233 – 235 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Miaio , M. , Pinto , A. , Carbone , A. , Zagonel , V. , Gloghini , A. , Marrota , C. , Cirillo , D. , Colombatti , A. , Ferrara , F. , Vecchio , L. D. and Ferrone , S.Differential expression of CD54/intercellular adhesion molecule‐1 in lymphoid leukemias and in lymphoproliferative disorder . Blood , 76 , 783 – 790 ( 1990. ). [PubMed] [Google Scholar]
  • 5. ) Natari , P. , Nicotra , M. R. , Cavaliere , R. , Bigotti , A. , Romano , G. , Temponi , M. and Ferrone , S.Differential expression of intercellular adhesion molecule‐1 in primary and metastatic melanoma lesions . Cancer Res. , 50 , 1271 – 1278 ( 1990. ). [PubMed] [Google Scholar]
  • 6. ) Dustin , M. L. , Rothlein , R. , Bhan , A. K. , Dinarello , C. A. and Springer , T. A.Induction by IL‐1 and interferon‐γ: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM‐1) . J. Immunol. , 137 , 245 – 254 ( 1986. ). [PubMed] [Google Scholar]
  • 7. ) Pober , J. S. , Gimbrone , M. A. , Jr. , Lapierre , L. A. , Mendrick , D. L. , Fiers , W. , Rothlein , R. and Springer , T. A.Overlapping patterns of activation of human endothelial cells by interleukin‐1, tumor necrosis factor, and immune interferon . J. Immunol. , 137 , 1893 – 1896 ( 1986. ). [PubMed] [Google Scholar]
  • 8. ) Tsujisaki , M. , Imai , K. , Hirata , H. , Hanzawa , Y. , Masuya , J. , Nakano , T. , Sugiyama , T. , Matsui , M. , Hinoda , Y. and Yachi , A.Detection of circulating intercellular adhesion molecule‐1 antigen in malignant diseases . Clin. Exp. Immunol. , 85 , 3 – 8 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. ) Droz , D. , Patey , N. , Paraf , F. , Chretien , Y. and Gogusev , J.Composition of extracellular matrix and distribution of cell adhesion molecules in renal cell tumors . Lab. Invest. , 71 , 710 – 719 ( 1994. ). [PubMed] [Google Scholar]
  • 10. ) Janossy , G. , Tidman , N. , Papageorgiu , E. S. , Kung , P. C. and Goldstein , G.Distribution of T‐lymphocyte subsets in the human bone marrow and thymus: an analysis with monoclonal antibodies . J. Immunol. , 126 , 1608 – 1613 ( 1981. ). [PubMed] [Google Scholar]
  • 11. ) Reinherz , E. , Kung , P. C. , Goldstein , G. , Levey , R. H. and Schlossmann , S. F.Discrete stage of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T‐cell lineage . Proc. Natl. Acad. Sci. USA , 77 , 1588 – 1592 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. ) Xiang , J. , Roder , J. and Hozumi , N.Production of murine V‐human Cγ1 chimeric anti‐TAG72 antibody using V region cDNA amplified by PCR . Mol. Immunol. , 27 , 809 – 817 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Khazaeri , M. B. , Salen , M. N. , Liu , P. , Meredith , R. F. , Wheeler , R. H. , Baker , T. S. , King , D. , Seche , R. D. , Allen , L. , Rogers , K. , Colecher , D. , Schlom , J. , Shichat , D. and Lobuglio , A. F.Pharmacokinetics and immune response of 131I‐chimeric mouse/human B72.3 (human γ4) monoclonal antibody in humans . Cancer Res. , 51 , 5461 – 5466 ( 1991. ). [PubMed] [Google Scholar]
  • 14. ) Meredith , R. F. , Obuglio , A. F. , Plott , W. E. , Orr , R. A. , Brezovich , I. A. , Russell , C. D. , Harvey , E. B. , Yester , M. V. , Wagner , A. J. , Spencer , S. A. , Wheeler , R. H. , Saleh , M. N. , Rogers , K. J. , Polansky , A. , Salter , M. M. and Khazaeri , M. B.Pharmacokinetics, immune response, and biodistribution of iodine‐131‐labeled chimeric mouse/human IgG, k 17‐1A monoclonal antibody . J. Nucl. Med. , 32 , 1162 – 1168 ( 1991. ). [PubMed] [Google Scholar]
  • 15. ) Kabat , E. A. , Wu , T. T. , Reid‐Miller , M. , Perry , H. M. and Gottesman , K. S. “ Sequences of Proteins of Immunological Interest ,” 4th Ed. ( 1987. ). U. S. Dept. Health and Human Services; , Washington , D.C. [Google Scholar]
  • 16. ) Davis , L. G. , Dibner , M. D. and Battey , J. F.Guanidine isothiocyanate preparation of total RNA . In “ Basic Methods in Molecular Biology .” ed. , Davis L. G. , Dibner M. D. and Battey J. F. , pp. 91 – 96 ( 1986. ). Elsevier; , New York . [Google Scholar]
  • 17. ) Kawasaki , E. S. , Innis , M. A. , Gelfand , D. H. , Sninsky , J. J. and White , T. J.Amplification of RNA . In “ PCR Protocols. A Guide to Methods and Applications .” ed. , Innis M. A.et al. , pp. 21 – 27 ( 1990. ). Academic Press Inc. , San Diego . [Google Scholar]
  • 18. ) Potter , H. , Weir , L. and Leder , P.Enhancer‐dependent expression of human k immunoglobulin genes introduced into mouse pre‐B lymphocytes by electroporation . Proc. Natl. Acad. Sci. USA , 81 , 7161 – 7165 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. ) Ey , P. L. , Prowes , S. J. and Jenkin , C. R.Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A‐Sepharose . Immunochemistry , 15 , 429 – 436 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Greenwood , F. C. , Hunter , W. M. and Glover , J. S.The preparation of 131I‐labeled human growth hormone of high specific radioactivity . Biochem. J. , 89 , 114 – 117 ( 1963. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. ) Mather , S. J. and Ellison , D.Reduction‐mediated technetium‐99m labeling of monoclonal antibodies ? J. Nucl. Med. , 31 , 692 – 697 ( 1990. ). [PubMed] [Google Scholar]
  • 22. ) Scatchard , G.The attraction of proteins for small molecules and ions . Ann. N. Y. Acad. Sci. , 51 , 660 – 664 ( 1949. ). [Google Scholar]
  • 23. ) Ishida , T. , Tsujisaki , M. , Hinoda , Y. , Imai , K. and Yachi , A.Establishment and characterization of mouse‐human chimeric monoclonal antibody to erbB‐2 product . Jpn. J. Cancer Res. , 85 , 172 – 178 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. ) Sun , L. K. , Curtis , P. , Rakowics‐Szulczynska , E. , Ghrayeb , J. , Chang , N. , Morrison , S. L. and Koprowsski , H.Chimeric antibody with human constant regions and mouse variable regions directed against carcinoma associated 17‐1A . Proc. Natl. Acad. Sci. USA , 84 , 214 – 218 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. ) Lou , A. Y. , Robinson , R. R. , Hellstrom , K. E. , Murray , E. D. , Jr. , Chang , C. P. and Hellstrom , I.Chimeric mouse‐human IgG1 antibody that can mediate lysis of cancer cells . Proc. Natl. Acad. Sci. USA , 84 , 3439 – 3443 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. ) Goodman , G. E. , Hellstrom , I. , Brodzinsky , L. , Nicaise , C. , Kulander , B. , Hummel , D. and Hellstrom , K. E.Phase I trial of murine monoclonal antibody L6 in breast, colon, ovarian, and lung cancer . J. Clin. Oncol. , 8 , 1084 – 1092 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 27. ) Goodmann , G. E. , Hellstrom , I. , Yelton , D. E. , Murray , J. L. , O'horo , S. , Meaker , E. R. , Zeigler , L. , Palazollo , P. , Nicaise , J. , Usakewicz , J. and Hellstrom , K. E.Phase I trial of chimeric (human‐mouse) monoclonal antibody L6 in patients with non‐small‐cell lung, colon, and breast cancer . Cancer Immunol. Immunother. , 36 , 267 – 273 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. ) Velders , M. P. , Litvinov , S. V. , Warnaar , S. O. , Gorter , A. , Fleuren , G. J. , Zurawsky , V. R. , Jr. and Coney , L. R.New chimeric anti‐pancarcinoma monoclonal antibody with superior cytotoxicity‐mediating potency . Cancer Res. , 54 , 1753 – 1759 ( 1994. ). [PubMed] [Google Scholar]
  • 29. ) Naganuma , H. , Kiessling , R. , Patarroyo , M. , Hansson , M. , Handgretinger , R. and Gronberg , A.Increased susceptibility of INF‐γ‐treated neuroblastoma cells to lysis by lymphokine‐activated killer cells: participation of ICAM‐1 induction on target cells . Int. J. Cancer , 47 , 527 – 532 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 30. ) Anichini , D. , Motarini , R. , Alberti , S. , Mantovani , A. and Parmiani , G.T Cell‐receptor engagement and tumor ICAM‐1 up‐regulation are required to by‐pass low susceptibility of melanoma cell to autologous CTL‐mediated lysis . Int. J. Cancer , 53 , 994 – 1001 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 31. ) Webb , D. S. A. , Mostowski , H. S. and Gerrard , T. L.Cytokine‐induced enhancement of ICAM‐1 expression results in increased vulnerability of tumor cells to monocyte‐mediated lysis . J. Immunol. , 146 , 3682 – 3686 ( 1991. ). [PubMed] [Google Scholar]
  • 32. ) Jonjic , N. , Alberti , S. , Peri , G. , Jilek , P. , Anichini , A. , Parmiani , G. and Mantovani , A.Heterogeneous susceptibility of human melanoma clones to monocyte cytotoxicity: role of ICAM‐1 defined by antibody blocking and gene transfer . Eur. J. Immunol. , 22 , 2255 – 2260 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 33. ) Huag , C. E. , Colvin , R. B. , Delmonico , F. L. , Auchincloss , H. , Tolkoffrubin , N. , Preffer , F. I. , Rothlein , R. , Norris , S. , Scharaschmidt , L. and Cosimi , A. B.A phase I trial of immunosuppression with anti‐ICAM‐1(CD54) mAb in renal allograft recipients . Transplantation , 55 , 766 – 773 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 34. ) Kavanaugh , A. F. , Nichols , L. A. and Lipsky , P. E.Treatment of refractory rheumatoid arthritis with a monoclonal antibody to intercellular adhesion molecule‐1 . Arthritis Rheum. , 37 , 992 – 999 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 35. ) Hirano , T. , Tomiyoshi , K. , Watanabe , N. , Tateno , M. , Oriuchi , N. , Inoue , T. and Endo , K.Technetium‐99m‐labeled anti‐fibrin monoclonal antibody accumulation in an inflammatory focus . J. Nucl. Med. , 33 , 1181 – 1182 ( 1992. ). [PubMed] [Google Scholar]
  • 36. ) Reuland , P. , Winker , K. H. , Heuchert , T. , Ruch , P. , Mueller‐Schauenburg , W. , Weller , S. and Feine , U.Detection of infection in post‐operative orthopedic patients with technetium‐99m‐labeled monoclonal antibodies against granulocytes . J. Nucl. Med. , 32 , 2209 – 2214 ( 1991. ). [PubMed] [Google Scholar]
  • 37. ) Sakahara , H. , Saga , T. , Hosono , M. , Endo , K. , Nakai , T. , Yamamuro , T. , Toyama , S. and Konishi , J.Direct labeling of monoclonal antibody with Tc‐99m and its biodistribution in mice . J. Nucl. Med. , 32 , 1099 ( 1991. ). [Google Scholar]
  • 38. ) Sung , C. , Shockley , T. R. , Morrison , P. F. , Dvorak , H. F. , Yarmush , M. L. and Dedrich , R. L.Predicted and observed effects of antibody affinity and antigen density on monoclonal antibody uptake in solid tumors . Cancer Res. , 52 , 377 – 384 ( 1992. ). [PubMed] [Google Scholar]
  • 39. ) Isobe , M. , Ohtani , H. , Yagita , H. , Okumura , K. , Strauss , H. W. and Yazaki , Y.Detection of cardiac rejection in mice by radioimmune scintigraphy using 123iodine‐labeled anti‐ICAM‐1 monoclonal antibody . Acta Cardiol. , 108 , 235 – 243 ( 1993. ). [PubMed] [Google Scholar]

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