Abstract
Hodgkin’s disease is an ideal target for immunotoxin therapy for several reasons. First, the Hodgkin/Reed-Sternberg (H-RS) cells, which are the putative malignant cells in this disease, have surface markers which are present only on a small minority of normal lymphoid cells. These markers are activation antigens recognized by monoclonal antibodies against the IL-2 receptor alpha-chain (CD25) (Agnarsson and Kadin, 1989), CD30 (Stein et al., 1985), and a 70kDa protein recognized by the unclustered IRac antibody (Hsu et al., 1987). Second, the majority of cells found within Hodgkin tumors are non-malignant reactive cells. Thus, the number of cells that needs to be killed is small. Third, Hodgkin tumors are usually well vascularized (Kaplan, 1980), suggesting that access of the immunotoxin to the target cells should be easier than it is, for example, in solid tumors. Fourth, Hodgkin’s disease responds well to chemotherapy. It is therefore feasible to eradicate bulky disease by conventional therapy and then administer immunotoxins to kill residual tumor cells.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Agnarsson, B. A. and Kadin, M. E., 1989, The imunophenotype of Reed-Sternberg cells. A study of 50 cases of Hodgkin’s disease using fixed frozen tissue, Cancer, 63:2083.
Bernhard, M. I., Foon, K. A., Oeltmann, T. N., Key, M. E., Hwang, K. M., Clarke, G. C, Christensen, W. L., Hoyer, L. C, Hanna, M. G. and Oldham, R. K., 1983, Guinea pig line 10 hepatocarcinoma model: characterization of monoclonal antibody and in vivo effect of unconjugated antibody and antibody conjugated to diphteria toxin A-chain, Cancer Res., 43:4420.
Byers, V. S., Pimm, M. V., Scannon, P. J., Pawluzyk, S. I. and Baldwin, R. W., 1987, Inhibition of growth of human tumor xenographs in athymic mice treated with ricin toxin A-chain-monoclonal-antibody 791T/36 conjugates, Cancer Res., 47:5042.
Engert, A., Burrows, F., Jung, W., Tazzari, P. L., Stein, H., Pfreundschuh, M., Diehl V. and Thorpe, P., 1990, Evaluation of ricin A-chain containing immunotoxins directed against CD30 as potential reagents for the treatment of Hodgkin’s disease, Cancer Res., 50:84.
Engert, A., Martin, G., Amlot, P., Wijdenes, J., Diehl V. and Thorpe, P., 1991, Immunotoxins constructed with CD25 monoclonal antibodies and deglycosylated ricin A-chain have potent antitumor effects against human Hodgkin cells in vitro and solid Hodgkin tumors in mice, Int. J. Cancer, 49:450.
Engert, A., Martin, G., Pfreundschuh, M. Amlot, P. Hsu, S. M., Diehl V. and Thorpe P., 1990, Antitumor effects of ricin A-chain immunotoxins from intact antibodies and Fab’ fragments on solid human Hodgkin’s disease tumors in mice, Cancer Res., 50:2929.
Fulton, R. J., Uhr, J. W. and Vitetta, E. S., 1988, In vivo therapy of the BCL tumor: effect of immunotoxin valency and deglycosylation of the ricin A-chain, Cancer Res., 48:2626.
Hara, H. Luo, Y. Haruta, Y. and Seon, B. K., 1988, Efficient transplantation of human T-leukemia cells into nude mice and induction of complete regression of the transplanted distinct tumors by ricin A-chain conjugates of monoclonal antibodies SNS and SN6, Cancer Res., 48:4673.
Hara, H., Luo, Y., Press, O.W., Martin, P. J., Thorpe, P. E. and Vitetta, E. S., 1988, Ricin A-chain containing immunotoxins directed against different epitopes on the CD3 molecule differ in their ability to kill normal and malignant T cells, J. Immunol., 141:4410.
Hsu, S.-M., Ho. Y.-S. and Hsu, P.-L., 1987, Effect of monoclonal antibodies anti-2H9, anti-IRac, and anti-HeFi-1 on the surface antigens of Reed-Sternberg cells, J. Nat. Cancer Inst., 79:1091.
Janossy, G. and Amlot, P., 1987, Immunofluorescence and immunohistology, in: C. G. B. Klaus, ed., “Lymphocytes: A Practical Approach”, IRL Press, Oxford.
Kaplan, H.S., 1980, Hodgkin’s disease: unfolding concepts concerning its nature, management and prognosis, Cancer, 45:2439.
Shen, G. L., Li, J. L., Ghetie, M. A., Ghetie, V., May, R. D., Till, M., Brown, A. N. F., Relf, M. G., Knowles, P., Uhr, J. W., Janossy, G., Amlot, P., Vitetta, E. E. and Thorpe, P. E., 1988, Evaluation of four CD22 antibodies as ricin-A-chain-containing immunotoxins for the in vivo therapy of human B-cell leukemias and lymphomas, Int. J. Cancer, 42:792.
Stein, H., Masan, D. Y., Gerdes, J., O’Connor, N., Wainscoat, J., Pallesen, G., Gatter, K., Falini, B., Delsol, G., Lembke, H., Schwarting, R. and Lennert, K., 1985, The expression of the Hodgkin’s disease-associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Sterriberg-Reed cells and histiocytic malignancies are derived from activated lymphoid cells, Blood, 66:848.
Thorpe, P. E., Wallace, P. M., Khowles, P. P., Relf, M. G., Brown, A. N. F. Watson, G. J., Blakey, D. C. and Newell, D. R., 1988, Improved anti-tumor effects of immunotoxins prepared with deglycosylated ricin A-chain and hindered disulfide linkages, Cancer Res., 48:6396.
Till, M., May, R. D., Uhr, I. W., Thorpe, P. E. and Vitetta, E. S., 1988, An assay that predicts the ability of monoclonal antibodies to form potent ricin A-chain-containing immunotoxins, Cancer Res., 48:1119.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1992 Springer Science+Business Media New York
About this chapter
Cite this chapter
Engert, A., Thorpe, P. (1992). The Development of Ricin A-Chain Immunotoxins for Clinical Trials in Patients with Hodgkin’s Disease. In: Gregoriadis, G., Florence, A.T., Poste, G. (eds) Targeting of Drugs 3. NATO ASI Series, vol 238. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2938-5_2
Download citation
DOI: https://doi.org/10.1007/978-1-4615-2938-5_2
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6276-0
Online ISBN: 978-1-4615-2938-5
eBook Packages: Springer Book Archive