Serotherapy and Bone Marrow Transplantation

  • Jerome Ritz
  • Stephen E. Sallan
  • Robert C. BastJr.
  • Tak Takvorian
  • Stuart F. Schlossman


Within the human hematopoietic system, monoclonal antibodies have been used to identify a large number of surface antigens expressed by both normal and malignant cells, and in many instances it has now been possible to ascribe specific functions to individual cell surface molecules. Since monoclonal antibodies can be produced in large quantities and can be easily purified, it has also been possible to explore the potential therapeutic applications of these unique reagents. As a result, several different antibodies have been used in serotherapy trials in patients with refractory leukemia or lymphoma1–5 and in several solid tumors.6 In each of these studies, antibodies have been infused, with the hopes that antibody-bound tumor cells would subsequently be eliminated by natural effector mechanisms. In addition, monoclonal antibodies have also been utilized under more controlled circumstances in vitro in order to deplete specific target cells from bone marrow prior to either autologous7 or allogeneic marrow transplantation.8 In order to demonstrate the potential utility of these reagents, this chapter will focus on the specific clinical applications of monoclonal antibodies in patients with acute lymphoblastic leukemia (ALL). Although other clinical situations and other monoclonal antibodies with different specificity will undoubtedly present unique problems, much of the information gained in patients with ALL will be applicable to other leukemias and lymphomas and, to a lesser extent, to solid tumors as well.


Total Body Irradiation Autologous Bone Marrow Transplantation Residual Tumor Cell Allogeneic Marrow Marrow Harvest 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Nadler, L. M., Stashenko, P., Hardy, R., Kaplan, W. D., Button, L. N., Kufe, D. W., Antman, K. H., and Schlossman, S. F., 1980, Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma associated antigen, Cancer Res. 40:3147–3154.PubMedGoogle Scholar
  2. 2.
    Ritz, J., Pesando, J. M., Sallan, S. E., Clavell, L. A., Notis-McConarty, J., Rosenthal, P., and Schlossman, S. F., 1981, Serotherapy of acute lymphoblastic leukemia with monoclonal antibody, Blood 58:141–152.PubMedGoogle Scholar
  3. 3.
    Miller, R. A., Oseroff, A. R., Stratte, P. T., and Levy, R., 1983, Monoclonal antibody therapeutic trials in seven patients with T cell lymphoma, Blood 62:988–995.PubMedGoogle Scholar
  4. 4.
    Dillman, R. O., Shawler, D. L., Sobol, R. E., Collins, H. A., Beuregard, J. C., Wormsley, S. B., and Royston, I., 1982, Murine monoclonal antibody therapy in two patients with chronic lymphocytic leukemia, Blood 59:1036–1045.PubMedGoogle Scholar
  5. 5.
    Miller, R. A., Maloney, D. A., Warnke, R., and Levy, R., 1982, Treatment of B cell lymphoma with monoclonal anti-idiotype antibody, N. Engl. J. Med. 306:517–522.PubMedCrossRefGoogle Scholar
  6. 6.
    Sears, H. F., Herlyn, D., Steplewski, Z., and Koprowski, H., 1984, Effects of monoclonal antibody immunotherapy on patients with gastrointestinal adenocarcinoma, J. Biol. Resp. Modif. 3:138–150.Google Scholar
  7. 7.
    Ritz, J., Sallan, S. E., Bast, R. C., Lipton, J. M., Clavell, L. A., Feeney, M., Hercend, T., Nathan, D. C., and Schlossman, S. F., 1982, Autologous bone marrow transplantation in CALLA positive acute lymphoblastic leukemias after in vitro treatment with J5 monoclonal antibody and complement, Lancet ii:60–63.CrossRefGoogle Scholar
  8. 8.
    Reinherz, E. L., Geha, C., Rappeport, J. M., Wilson, M., Penta, A. C., Hussey, R. E., Fitzgerald, K. A., Daley, J., Levine, H., Rosen, F. S., and Schlossman, S. F., 1982, Immune reconstitution in severe combined immunodeficiency following transplantation with T lymphocyte depleted HLA haplotype mismatched bone marrow, Proc. Natl. Acad. Sci. USA 79:6047–6051.PubMedCrossRefGoogle Scholar
  9. 9.
    Ritz, J., Pesando, J. M., Notis-McConarty, J., Lazarus, H., and Schlossman, S. F., 1980, A monoclonal antibody to human acute lymphoblastic leukemia antigen, Nature 283:583–585.PubMedCrossRefGoogle Scholar
  10. 10.
    Greaves, M. F., Hariri, G., Newman, R. A., Sutherland, D. R., Ritter, M. A., and Ritz, J., 1983, Selective expression of the common acute lymphoblastic leukemia (gp100) antigen on immature lymphoid cells and their malignant counterparts, Blood 61:628–639.PubMedGoogle Scholar
  11. 11.
    Ritz, J., Nadler, L. M., Bhan, A. K., Notis-McConarty, J., Pesando, J. M., and Schlossman, S. F., 1981, Expression of common acute lymphoblastic leukemia antigen (CALLA) by lymphomas of B cell and T cell lineage, Blood 58:648–652.PubMedGoogle Scholar
  12. 12.
    Clavell, L. A., Lipton, J. M., Bast, R. C., Kudisch, M., Pesando, J. M., Schlossman, S. F., and Ritz, J., 1981, Absence of common ALL antigen on bi-potent myeloid, erythroid and granulocyte progenitors, Blood 58:333–336.PubMedGoogle Scholar
  13. 13.
    Hokland, P., Rosenthal, P., Griffin, J. D., Nadler, L. M., Daley, J. F., Hokland, M., Schlossman, S. F., and Ritz, J., 1983, Purification and characterization of fetal hematopoietic cells which express the common acute lymphoblastic leukemia antigen (CALLA), J. Exp. Med. 157:114–129.PubMedCrossRefGoogle Scholar
  14. 14.
    Cossman, J., Neckers, L. M., Leonard, W. J., and Greene, W. C., 1983, Polymorphonuclear neutrophils express the common acute lymphoblastic leukemia antigen, J. Exp. Med. 157:1064–1069.PubMedCrossRefGoogle Scholar
  15. 15.
    Braun, M. P., Martin, P. J., Ledbetter, J. A., and Hansen, J. A., 1983, Granulocytes and cultured human fibroblasts express common acute lymphoblastic leukemia associated antigens, Blood 61:718–725.PubMedGoogle Scholar
  16. 16.
    Metzgar, R. S., Borowitz, M. F., Jones, N. H., and Dowell, B. L., 1981, Distribution of common acute lymphoblastic leukemia antigen in nonhematopoietic tissues, J. Exp. Med. 154:1249–1254.PubMedCrossRefGoogle Scholar
  17. 17.
    Hercend, T., Nadler, L. M., Pesando, J. M., Reinherz, E. L., Schlossman, S. F., and Ritz, J., 1981, Expression of a 26,000 dalton glycoprotein on activated human T cells, Cell. Immunol. 64:192–199.PubMedCrossRefGoogle Scholar
  18. 18.
    LeBien, T., Kersey, J., Nakazawa, S., Minato, K., and Minowada, J., 1982, Analysis of human leukemia/lymphoma cell lines with monoclonal antibodies BA-1, BA-2 and BA-3, Leukemia Res. 6:299–305.CrossRefGoogle Scholar
  19. 19.
    Jones, N. H., Borowitz, M. J., and Metzgar, R. S., 1982, Characterization and distribution of a 24,000 molecular weight antigen defined by a monoclonal antibody (DU-ALL-1) elicited to common acute lymphoblastic leukemia (cALL) cells, Leukemia Res. 6:449–464.CrossRefGoogle Scholar
  20. 20.
    Komada, Y., Peiper, S. C., Melvin, S. L., Metzgar, D. W., Tarnowski, B. H., and Green, A. A., 1983, A monoclonal antibody (SJ-9A4) to p24 present on common ALLs, neuroblastomas and platelets. I. Characterization and development of a unique radioimmunometric assay, Leukemia Res. 7:487–498.CrossRefGoogle Scholar
  21. 21.
    Ritz, J., Pesando, J. M., Notis-McConarty, J., and Schlossman, S. F., 1980, Modulation of human acute lymphoblastic leukemia antigen induced by monoclonal antibody in vitro, J. Immunol. 125:1506–1514.PubMedGoogle Scholar
  22. 22.
    Ritz, J., and Schlossman, S. F., 1982, Utilization of monoclonal antibodies in the treatment of leukemia and lymphoma, Blood 59:1–11.PubMedGoogle Scholar
  23. 23.
    Bast, R. C., Ritz, J., Lipton, J. M., Feeney, M., Sallan, S. E., Nathan, D. G., and Schlossman, S. F., 1983, Elimination of leukemic cells from human bone marrow using monoclonal antibody and complement, Cancer Res. 43:1389–1394.PubMedGoogle Scholar
  24. 24.
    Johnson, F. L., Thomas, E. D., Clark, B. S., Chard, R. L., Harmann, J. R., and Storb, R., 1981, A comparison of marrow transplantation with chemotherapy for children with acute lymphoblastic leukemia in second or subsequent remission, N. Engl. J. Med. 305:846–851.PubMedCrossRefGoogle Scholar
  25. 25.
    Bast, R. C., DeFabritiis, P., Lipton, J. M., Gelber, R., Maver, C., Nadler, L. M., Sallan, S. E., and Ritz, J., 1985, Elimination of malignant clonogenic cells from human bone marrow using multiple monoclonal antibodies and complement, Cancer Res. 45:499–503.PubMedGoogle Scholar
  26. 26.
    Nadler, L. M., Takvorian, T., Botnick, L., Bast, R. C., Finberg, R., Hellman, S., Canellos, G. P., and Schlossman, S. F., 1984, Anti-B1 monoclonal antibody and complement treated autologous bone marrow transplantation for relapsed B cell non-Hodgkin’s lymphoma, Lancet ii:427–434.CrossRefGoogle Scholar
  27. 27.
    Benjamin, D., Magrath, I. T., Douglass, E. C., and Corash, L. M., 1983, Derivation of lymphoma cell lines from microscopically normal bone marrow in patients with undifferentiated lymphomas: Evidence of occult bone marrow involvement, Blood 61:1017–1019.PubMedGoogle Scholar
  28. 28.
    Philips, G. L., Herzig, R. H., Lazarus, H. M., Fay, J. W., Wolff, S. N., Mill, W. B., Lin, H., Thomas, P. R. M., Glasgow, G. P., Shina, D. C., and Herzig, G. P., 1984, Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow, N. Engl. J. Med. 310:1557–1561.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Jerome Ritz
    • 1
    • 2
  • Stephen E. Sallan
    • 4
    • 2
  • Robert C. BastJr.
    • 1
    • 2
  • Tak Takvorian
    • 3
    • 2
  • Stuart F. Schlossman
    • 1
    • 2
  1. 1.Division of Tumor ImmunologyDana-Farber Cancer InstituteBostonUSA
  2. 2.Department of MedicineHarvard Medical SchoolBostonUSA
  3. 3.Division of Medical OncologyDana-Farber Cancer InstituteBostonUSA
  4. 4.Division of Pediatric OncologyDana-Farber Cancer InstituteBostonUSA

Personalised recommendations