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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.