Therapy of murine leukemia with monoclonal antibody against a normal differentiation antigen.
Open Access
- 1 March 1983
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 157 (3) , 828-842
- https://doi.org/10.1084/jem.157.3.828
Abstract
The ability of monoclonal antibodies against the Thy-1.1 differentiation antigen to inhibit the growth of transplanted syngeneic AKR/J SL2 leukemic cells has been previously demonstrated. In the present study we further examined therapy with monoclonal antibody of the IgG2a isotype, which was the most effective isotype studied. Intravenous infusion of ascites fluid containing the anti-Thy-1.1 monoclonal antibody 19-E12 1-2 h after tumor implantation led to inhibition of the growth of 3 X 10(5) but not 3 X 10(6) syngeneic SL2 leukemic cells. The achievement of the maximal therapeutic effect required the infusion of a dose containing 3.2 mg of antibody, which inhibited the growth of a subcutaneous inoculum of 3 X 10(5) SL2 leukemic cells in 83% of treated mice. Multiple doses of antibody were no more effective than a single dose given shortly after tumor implantation. The infusion of this relatively large 3.2-mg dose of antibody was required to infiltrate the subcutaneous space and saturate surface Thy-1.1 sites on leukemic cells in a subcutaneous tumor nodule. The failure of antibody to inhibit larger numbers of tumor cells was investigated. Growth of a subcutaneous tumor nodule in mice challenged with more than 3 X 10(5) cells resulted from the growth of Thy-1.1-bearing cells in spite of the presence of the infused anti-Thy-1.1 antibody on their surfaces. In contrast, metastatic growth was due to the emergence of variant leukemic cells lacking the Thy-1.1 antigen. Thus, treatment of transplanted T leukemic cells with an IgG2a anti-Thy-1.1 monoclonal antibody was effective in eliminating 3 X 10(5) antigen-bearing leukemic cells from the subcutaneous space and was very effective in preventing metastasis of leukemic cells expressing the target Thy-1.1 antigen. Therapy was limited by the failure of host mechanisms to eliminate larger numbers of subcutaneous leukemic cells coated with the infused antibody and by the emergence of variant leukemic cells lacking the target antigen.Keywords
This publication has 20 references indexed in Scilit:
- Anti-transferrin receptor monoclonal antibody and toxin–antibody conjugates affect growth of human tumour cellsNature, 1981
- RESPONSE OF CUTANEOUS T CELL LYMPHOMA TO THERAPY WITH HYBRIDOMA MONOCLONAL ANTIBODYThe Lancet, 1981
- Cytotoxicity Acquired by Conjugation of an Anti‐Thy1.1 Monoclonal Antibody and the Ribosome‐Inactivating Protein, GeloninEuropean Journal of Biochemistry, 1981
- Serotherapy of Malignant Disease1Published by S. Karger AG ,1980
- Suppression of Antibody-Sensitized Tumor Cells by Macrophages: Insufficient Supply or Activation of Macrophages within Large TumorsThe Journal of Immunology, 1979
- Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-SepharoseImmunochemistry, 1978
- Oncornaviruses produced by murine leukemia cells in cultureVirology, 1977
- Antibody-mediated suppression of grafted lymphoma. IV. Influence of time of tumor residency in vivo and tumor size upon the effectiveness of suppression by syngeneic antibody.The Journal of Experimental Medicine, 1976
- Continuous cultures of fused cells secreting antibody of predefined specificityNature, 1975
- Antibody-mediated suppression of grafted lymphoma. III. Evaluation of the role of thymic function, non-thymus-derived lymphocytes, macrophages, platelets, and polymorphonuclear leukocytes in syngeneic and allogeneic hosts.1975