Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Jun;87(11):4217–4221. doi: 10.1073/pnas.87.11.4217

Antibody-targeted photolysis: in vitro studies with Sn(IV) chlorin e6 covalently bound to monoclonal antibodies using a modified dextran carrier.

S L Rakestraw 1, R G Tompkins 1, M L Yarmush 1
PMCID: PMC54079  PMID: 1693435

Abstract

A monoclonal antibody-dextran-Sn(IV) chlorin e6 immunoconjugate was prepared by a technique involving the site-specific covalent modification of the monoclonal antibody oligosaccharide moiety. Dextran carriers were synthesized with a single chain-terminal hydrazide group, which was used as the coupling point between the carrier and the monoclonal antibody carbohydrate. Selective in vitro photolysis of SK-MEL-2 human malignant melanoma cells was accomplished using several conjugates prepared from anti-melanoma 2.1 (chromophore:antibody molar ratios, 6.8 and 11.2). Phototoxicity, as measured by clonogenic assay, was dependent on the delivered dose of 634-nm light and was observed only for conjugates that bound SK-MEL-2 cells. As judged by competitive inhibition radioimmunoassay, conjugates prepared in this fashion showed excellent retention of antigen binding activity relative to the unmodified antibody.

Full text

PDF
4217

Selected References

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

  1. Ben-Hur E., Rosenthal I., Leznoff C. C. Recovery of Chinese hamster cells following photosensitization by zinc tetrahydroxyphthalocyanine. J Photochem Photobiol B. 1988 Sep;2(2):243–252. doi: 10.1016/1011-1344(88)80007-1. [DOI] [PubMed] [Google Scholar]
  2. Björck L., Kronvall G. Purification and some properties of streptococcal protein G, a novel IgG-binding reagent. J Immunol. 1984 Aug;133(2):969–974. [PubMed] [Google Scholar]
  3. Blair A. H., Ghose T. I. Linkage of cytotoxic agents to immunoglobulins. J Immunol Methods. 1983 Apr 29;59(2):129–143. doi: 10.1016/0022-1759(83)90024-8. [DOI] [PubMed] [Google Scholar]
  4. Burkot T. R., Wirtz R. A., Lyon J. Use of fluorodinitrobenzene to identify monoclonal antibodies which are suitable for conjugation to periodate-oxidized horseradish peroxidase. J Immunol Methods. 1985 Nov 28;84(1-2):25–31. doi: 10.1016/0022-1759(85)90411-9. [DOI] [PubMed] [Google Scholar]
  5. Denstman S. C., Dillehay L. E., Williams J. R. Enhanced susceptibility to HPD-sensitized phototoxicity and correlated resistance to trypsin detachment in SV40 transformed IMR-90 cells. Photochem Photobiol. 1986 Feb;43(2):145–147. doi: 10.1111/j.1751-1097.1986.tb09506.x. [DOI] [PubMed] [Google Scholar]
  6. Firey P. A., Rodgers M. A. Photochemical properties of erythrocyte ghosts containing porphyrin. Photochem Photobiol. 1988 May;47(5):615–619. doi: 10.1111/j.1751-1097.1988.tb02756.x. [DOI] [PubMed] [Google Scholar]
  7. Garnett M. C., Embleton M. J., Jacobs E., Baldwin R. W. Preparation and properties of a drug-carrier-antibody conjugate showing selective antibody-directed cytotoxicity in vitro. Int J Cancer. 1983 May 15;31(5):661–670. doi: 10.1002/ijc.2910310520. [DOI] [PubMed] [Google Scholar]
  8. Ghose T. I., Blair A. H., Kulkarni P. N. Preparation of antibody-linked cytotoxic agents. Methods Enzymol. 1983;93:280–333. doi: 10.1016/s0076-6879(83)93050-1. [DOI] [PubMed] [Google Scholar]
  9. Hnatowich D. J., Layne W. W., Childs R. L., Lanteigne D., Davis M. A., Griffin T. W., Doherty P. W. Radioactive labeling of antibody: a simple and efficient method. Science. 1983 May 6;220(4597):613–615. doi: 10.1126/science.6836304. [DOI] [PubMed] [Google Scholar]
  10. Khaw B. A., Fallon F. T., Strauss H. W., Haber E. Myocardial infarct imaging of antibodies to canine cardiac myosin with indium-111-diethylenetriamine pentaacetic acid. Science. 1980 Jul 11;209(4453):295–297. doi: 10.1126/science.7384803. [DOI] [PubMed] [Google Scholar]
  11. Mew D., Wat C. K., Towers G. H., Levy J. G. Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-hematoporphyrin conjugates. J Immunol. 1983 Mar;130(3):1473–1477. [PubMed] [Google Scholar]
  12. Murayama A., Shimada K., Yamamoto T. Modification of immunoglobulin G using specific reactivity of sugar moiety. Immunochemistry. 1978 Aug;15(8):523–528. doi: 10.1016/0161-5890(78)90003-2. [DOI] [PubMed] [Google Scholar]
  13. O'Shannessy D. J., Quarles R. H. Labeling of the oligosaccharide moieties of immunoglobulins. J Immunol Methods. 1987 May 20;99(2):153–161. doi: 10.1016/0022-1759(87)90120-7. [DOI] [PubMed] [Google Scholar]
  14. Oldham R. K. Monoclonal antibodies in cancer therapy. J Clin Oncol. 1983 Sep;1(9):582–590. doi: 10.1200/JCO.1983.1.9.582. [DOI] [PubMed] [Google Scholar]
  15. Order S. E., Klein J. L., Ettinger D., Alderson P., Siegelman S., Leichner P. Phase I-II study of radiolabeled antibody integrated in the treatment of primary hepatic malignancies. Int J Radiat Oncol Biol Phys. 1980 Jun;6(6):703–710. doi: 10.1016/0360-3016(80)90226-6. [DOI] [PubMed] [Google Scholar]
  16. Oseroff A. R., Ohuoha D., Hasan T., Bommer J. C., Yarmush M. L. Antibody-targeted photolysis: selective photodestruction of human T-cell leukemia cells using monoclonal antibody-chlorin e6 conjugates. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8744–8748. doi: 10.1073/pnas.83.22.8744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pastan I., Willingham M. C., FitzGerald D. J. Immunotoxins. Cell. 1986 Dec 5;47(5):641–648. doi: 10.1016/0092-8674(86)90506-4. [DOI] [PubMed] [Google Scholar]
  18. Rodwell J. D., Alvarez V. L., Lee C., Lopes A. D., Goers J. W., King H. D., Powsner H. J., McKearn T. J. Site-specific covalent modification of monoclonal antibodies: in vitro and in vivo evaluations. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2632–2636. doi: 10.1073/pnas.83.8.2632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Shih L. B., Sharkey R. M., Primus F. J., Goldenberg D. M. Site-specific linkage of methotrexate to monoclonal antibodies using an intermediate carrier. Int J Cancer. 1988 Jun 15;41(6):832–839. doi: 10.1002/ijc.2910410610. [DOI] [PubMed] [Google Scholar]
  20. Steele J. K., Liu D., Stammers A. T., Deal H., Whitney S., Levy J. G. Suppressor deletion therapy. Selective elimination of T suppressor cells using a hematoporphyrin-conjugated monoclonal antibody. Targeted Diagn Ther. 1988;1:157–189. [PubMed] [Google Scholar]
  21. Thorpe P. E., Ross W. C. The preparation and cytotoxic properties of antibody-toxin conjugates. Immunol Rev. 1982;62:119–158. doi: 10.1111/j.1600-065x.1982.tb00392.x. [DOI] [PubMed] [Google Scholar]
  22. Youle R. J., Neville D. M., Jr Anti-Thy 1.2 monoclonal antibody linked to ricin is a potent cell-type-specific toxin. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5483–5486. doi: 10.1073/pnas.77.9.5483. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES