Mouse/human chimeric monoclonal antibody in man: kinetics and immune response (original) (raw)

Abstract

A mouse/human chimeric monoclonal antibody (mAb) composed of the variable regions of murine 17-1A mAb and the constant regions of human IgG-1K immunoglobulin was administered to 10 patients with metastatic colon cancer. Four patients received single infusion of 10 mg (n = 2) or 40 mg (n = 2). Six patients received three infusion of 10 mg (n = 3) or 40 mg (n = 3) at 2-week intervals. The pharmacokinetics were similar at both dose levels and at the second and third infusions. The plasma disappearance curves were best fit by a two-compartment model having a mean alpha T1/2 of 17.5 hr (range 13-23 hr) and a mean beta T1/2 of 100.5 hr (range 65-139 hr). One patient who received three 40-mg doses of chimeric IgG-1K 17-1A mAb (day 0, 14, and 28) was the only patient to exhibit a detectable but modest antibody reactivity to chimera on days 63 and 84. The antibody reactivity was inhibited by murine 17-1A mAb, indicating that the antibody response was directed to the murine variable region of the chimera. The patients had no toxic or allergic reactions. This chimeric form of 17-1A mAb has an approximate 6-fold longer circulation time and appears to be substantially less immunogenic than its murine counterpart. These characteristics may provide an advantage in the clinical application of such chimeric molecules in therapeutic trials in humans.

4220

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Dillman R. O., Shawler D. L., Dillman J. B., Royston I. Therapy of chronic lymphocytic leukemia and cutaneous T-cell lymphoma with T101 monoclonal antibody. J Clin Oncol. 1984 Aug;2(8):881–891. doi: 10.1200/JCO.1984.2.8.881. [DOI] [PubMed] [Google Scholar]
  2. Girardet C., Vacca A., Schmidt-Kessen A., Schreyer M., Carrel S., Mach J. P. Immunochemical characterization of two antigens recognized by new monoclonal antibodies against human colon carcinoma. J Immunol. 1986 Feb 15;136(4):1497–1503. [PubMed] [Google Scholar]
  3. Hale G., Dyer M. J., Clark M. R., Phillips J. M., Marcus R., Riechmann L., Winter G., Waldmann H. Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H. Lancet. 1988 Dec 17;2(8625):1394–1399. doi: 10.1016/s0140-6736(88)90588-0. [DOI] [PubMed] [Google Scholar]
  4. Houghton A. N., Mintzer D., Cordon-Cardo C., Welt S., Fliegel B., Vadhan S., Carswell E., Melamed M. R., Oettgen H. F., Old L. J. Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: a phase I trial in patients with malignant melanoma. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1242–1246. doi: 10.1073/pnas.82.4.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Khazaeli M. B., Saleh M. N., Wheeler R. H., Huster W. J., Holden H., Carrano R., LoBuglio A. F. Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. II. Pharmacokinetics and immune response. J Natl Cancer Inst. 1988 Aug 17;80(12):937–942. doi: 10.1093/jnci/80.12.937. [DOI] [PubMed] [Google Scholar]
  6. Liu A. Y., Robinson R. R., Hellström K. E., Murray E. D., Jr, Chang C. P., Hellström I. Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells. Proc Natl Acad Sci U S A. 1987 May;84(10):3439–3443. doi: 10.1073/pnas.84.10.3439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Liu A. Y., Robinson R. R., Murray E. D., Jr, Ledbetter J. A., Hellström I., Hellström K. E. Production of a mouse-human chimeric monoclonal antibody to CD20 with potent Fc-dependent biologic activity. J Immunol. 1987 Nov 15;139(10):3521–3526. [PubMed] [Google Scholar]
  8. LoBuglio A. F., Court W. S., Vinocur L., Maglott G., Shaw G. M. Immune thrombocytopenic purpura. Use of a 125I-labeled antihuman IgG monoclonal antibody to quantify platelet-bound IgG. N Engl J Med. 1983 Aug 25;309(8):459–463. doi: 10.1056/NEJM198308253090804. [DOI] [PubMed] [Google Scholar]
  9. LoBuglio A. F., Saleh M. N., Lee J., Khazaeli M. B., Carrano R., Holden H., Wheeler R. H. Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. I. Clinical aspects. J Natl Cancer Inst. 1988 Aug 17;80(12):932–936. doi: 10.1093/jnci/80.12.932. [DOI] [PubMed] [Google Scholar]
  10. Meeker T. C., Lowder J., Maloney D. G., Miller R. A., Thielemans K., Warnke R., Levy R. A clinical trial of anti-idiotype therapy for B cell malignancy. Blood. 1985 Jun;65(6):1349–1363. [PubMed] [Google Scholar]
  11. Midgley A. R., Jr Radioimmunoassay: a method for human chorionic gonadotropin and human luteinizing hormone. Endocrinology. 1966 Jul;79(1):10–18. doi: 10.1210/endo-79-1-10. [DOI] [PubMed] [Google Scholar]
  12. Morell A., Terry W. D., Waldmann T. A. Metabolic properties of IgG subclasses in man. J Clin Invest. 1970 Apr;49(4):673–680. doi: 10.1172/JCI106279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Morrison S. L., Johnson M. J., Herzenberg L. A., Oi V. T. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6851–6855. doi: 10.1073/pnas.81.21.6851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Morrison S. L. Transfectomas provide novel chimeric antibodies. Science. 1985 Sep 20;229(4719):1202–1207. doi: 10.1126/science.3929380. [DOI] [PubMed] [Google Scholar]
  15. Neuberger M. S., Williams G. T., Mitchell E. B., Jouhal S. S., Flanagan J. G., Rabbitts T. H. A hapten-specific chimaeric IgE antibody with human physiological effector function. Nature. 1985 Mar 21;314(6008):268–270. doi: 10.1038/314268a0. [DOI] [PubMed] [Google Scholar]
  16. Nishimura Y., Yokoyama M., Araki K., Ueda R., Kudo A., Watanabe T. Recombinant human-mouse chimeric monoclonal antibody specific for common acute lymphocytic leukemia antigen. Cancer Res. 1987 Feb 15;47(4):999–1005. [PubMed] [Google Scholar]
  17. Pimm M. V., Perkins A. C., Armitage N. C., Baldwin R. W. The characteristics of blood-borne radiolabels and the effect of anti-mouse IgG antibodies on localization of radiolabeled monoclonal antibody in cancer patients. J Nucl Med. 1985 Sep;26(9):1011–1023. [PubMed] [Google Scholar]
  18. SOLOMON A., WALDMANN T. A., FAHEY J. L. Clinical and experimental metabolism of normal 6.6s gamma-globulin in normal subjects and in patients with macroglobulinemia and multiple myeloma. J Lab Clin Med. 1963 Jul;62:1–17. [PubMed] [Google Scholar]
  19. Scheinberg D. A., Houghton A. N. Current status of antitumor therapy with monoclonal antibodies. Oncology (Williston Park) 1987 May;1(3):31–40. [PubMed] [Google Scholar]
  20. Shaw D. R., Harrison G., Sun L. K., Shearman C., Ghrayeb J., McKinney S., Daddona P. E., LoBuglio A. F. Human lymphocyte and monocyte lysis of tumor cells mediated by a mouse/human IgG1 chimeric monoclonal antibody. J Biol Response Mod. 1988 Apr;7(2):204–211. [PubMed] [Google Scholar]
  21. Shaw D. R., Khazaeli M. B., LoBuglio A. F. Mouse/human chimeric antibodies to a tumor-associated antigen: biologic activity of the four human IgG subclasses. J Natl Cancer Inst. 1988 Dec 7;80(19):1553–1559. doi: 10.1093/jnci/80.19.1553. [DOI] [PubMed] [Google Scholar]
  22. Shaw D. R., Khazaeli M. B., Sun L. K., Ghrayeb J., Daddona P. E., McKinney S., LoBuglio A. F. Characterization of a mouse/human chimeric monoclonal antibody (17-1A) to a colon cancer tumor-associated antigen. J Immunol. 1987 Jun 15;138(12):4534–4538. [PubMed] [Google Scholar]
  23. Spitler L. E., del Rio M., Khentigan A., Wedel N. I., Brophy N. A., Miller L. L., Harkonen W. S., Rosendorf L. L., Lee H. M., Mischak R. P. Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. Cancer Res. 1987 Mar 15;47(6):1717–1723. [PubMed] [Google Scholar]
  24. Sun L. K., Curtis P., Rakowicz-Szulczynska E., Ghrayeb J., Chang N., Morrison S. L., Koprowski H. Chimeric antibody with human constant regions and mouse variable regions directed against carcinoma-associated antigen 17-1A. Proc Natl Acad Sci U S A. 1987 Jan;84(1):214–218. doi: 10.1073/pnas.84.1.214. [DOI] [PMC free article] [PubMed] [Google Scholar]