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. 1991 Nov;64(5):872–874. doi: 10.1038/bjc.1991.416

Histamine, leukotriene C4 and interleukin-2 increase antibody uptake into a human carcinoma xenograft model.

T W Hennigan 1, R H Begent 1, T G Allen-Mersh 1
PMCID: PMC1977450  PMID: 1931608

Abstract

Systemically administered radiolabelled anti-tumour antibody is ineffective in treating the majority of patients with liver metastasis from colorectal carcinoma. We have assessed whether agents which increase capillary permeability can increase tumour uptake of antibody isotope conjugate. We developed a xenograft model of colorectal carcinoma using an antibody directed against carcinoembryonic antigen (CEA). Tumours were grown subcutaneously in the hind limbs of athymic rats to derive their circulation from the femoral artery. Cannulae were placed in the common iliac artery and iliolumbar vein. Antibody was delivered systemically, regionally and regionally with histamine, leukotriene C4 and interleukin-2. Regionally administered anti-CEA antibody resulted in a significantly greater (P = 0.004) tumour to normal tissue ratio (1.66, s.d. = 0.68) compared to systematically administered antibody (1.25, s.d. = 0.73). The addition of vasoactive drugs produced an approximately 3-fold increase with an increase to a mean tumour:liver ratio of 3.24 (s.d. = 1.39) for histamine (P less than 0.001 compared to systemic delivery), 3.21 (s.d. = 1.13, P less than 0.001) for leukotriene C4 and 3.80 (s.d. = 1.53, P less than 0.001) for interleukin-2. The addition of histamine significantly (P = 0.004) increased the mean tumour to liver ratio (1.73, s.d. = 0.44) of non-specific antibody uptake compared with either systemic (1.12, s.d. = 0.24) or regional delivery (1.25, s.d. = 0.54) of non-specific antibody alone. Increasing tumour capillary permeability can produce a significant clinically useful increase in tumour uptake of antibody-isotope conjugate.

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Selected References

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  1. Badr K. F., Baylis C., Pfeffer J. M., Pfeffer M. A., Soberman R. J., Lewis R. A., Austen K. F., Corey E. J., Brenner B. M. Renal and systemic hemodynamic responses to intravenous infusion of leukotriene C4 in the rat. Circ Res. 1984 May;54(5):492–499. doi: 10.1161/01.res.54.5.492. [DOI] [PubMed] [Google Scholar]
  2. Begent R. H., Ledermann J. A., Green A. J., Bagshawe K. D., Riggs S. J., Searle F., Keep P. A., Adam T., Dale R. G., Glaser M. G. Antibody distribution and dosimetry in patients receiving radiolabelled antibody therapy for colorectal cancer. Br J Cancer. 1989 Sep;60(3):406–412. doi: 10.1038/bjc.1989.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dykes P. W., Bradwell A. R., Chapman C. E., Vaughan A. T. Radioimmunotherapy of cancer: clinical studies and limiting factors. Cancer Treat Rev. 1987 Jun;14(2):87–106. doi: 10.1016/0305-7372(87)90042-9. [DOI] [PubMed] [Google Scholar]
  4. Frölich J. C., Yoshizawa M. Renal vascular effects of leukotriene C4 in the isolated perfused kidney of the rat. Br J Pharmacol. 1987 Oct;92(2):311–318. doi: 10.1111/j.1476-5381.1987.tb11325.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Rosenstein M., Ettinghausen S. E., Rosenberg S. A. Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2. J Immunol. 1986 Sep 1;137(5):1735–1742. [PubMed] [Google Scholar]
  7. Sands H., Jones P. L., Neacy W. P., Shah S. A., Gallagher B. M. Site-related differences in the localization of the monoclonal antibody OX7 in SL2 and SL1 lymphomas. Cancer Immunol Immunother. 1986;22(3):169–175. doi: 10.1007/BF00200028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Sands H., Jones P. L., Shah S. A., Palme D., Vessella R. L., Gallagher B. M. Correlation of vascular permeability and blood flow with monoclonal antibody uptake by human Clouser and renal cell xenografts. Cancer Res. 1988 Jan 1;48(1):188–193. [PubMed] [Google Scholar]
  9. Sands H., Shah S. A., Gallagher B. M. Vascular volume and permeability of human and murine tumors grown in athymic mice. Cancer Lett. 1985 May;27(1):15–21. doi: 10.1016/0304-3835(85)90004-7. [DOI] [PubMed] [Google Scholar]
  10. Staab H. J., Anderer F. A. Growth of human colonic adenocarcinoma and development of serum CEA in in athymic mice. I: Strict correlation of tumour size and mass with serum CEA concentration during logarithmic growth. Br J Cancer. 1982 Dec;46(6):841–847. doi: 10.1038/bjc.1982.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Tannock I. F., Steel G. G. Quantitative techniques for study of the anatomy and function of small blood vessels in tumors. J Natl Cancer Inst. 1969 May;42(5):771–782. [PubMed] [Google Scholar]
  12. Vaupel P. Interrelationship between mean arterial blood pressure, blood flow, and vascular resistance in solid tumor tissue of DS-carcinosarcoma. Experientia. 1975 May 15;31(5):587–589. doi: 10.1007/BF01932474. [DOI] [PubMed] [Google Scholar]

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