Specific in vivo localization of monoclonal antibodies directed against the Thy 1.1 antigen
L L Houston, R C Nowinski, I D Bernstein
1980
Journal of Immunology
The ability of a homogeneous IgG2a monoclonal antibody against Thy 1.1 antigen to selectively bind to Thy 1-containing tissues in congenic AKR mice was tested as a function of time. The rapid clearance from blood of ['25J+labeled 19-F12(M) antibody from AKR/J (Thy 1.1) mice, compared to that of AKR/Cu (Thy 1.2) mice, was consistent with the specificity of the antibody and its homing into target tissues. The selective localization of this antibody into lymphatic tissues was time dependent. At
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... imal times (20 hr post-injection) the lymph nodes of AKR/J mice contained 9-fold more antibody than the lymph nodes of AKR/Cu mice. Localization of the F(ab')2 fragment of 19-F12(M) antibody into lymphatic tissues was even more striking. Clearance of the F(ab')2 from blood was extremely rapid, and at 16 hr after injection, the lymph nodes of AKR/J mice contained 144-fold more F(ab')z than did the lymph nodes of AKR/Cu mice. When localization within specific organs was determined relative to nonimmune IgG2a the F(ab')z concentrated into lymph nodes and spleen of AKR/J mice by factors in excess of 475 and 250, respectively. In contrast, neither intact 19-F12(M) antibody or its F(ab')z fragment were concentrated in the lymphatic tissues of AKR/Cu mice. These studies demonstrate that monoclonal antibodies against Thy 1.1 antigen possess sufficient specificity, homogeneity, and avidity to selectively localize in appropriate target tissues in uiuo. The search for specific reagents that can be directed against tumor cells has been pursued for many years. Antibodies have been considered likely candidates since they display an extremely narrow range of reactivity. Yet, despite these apparent advantages, most attempts to treat tumors with antibodies or to demonstrate specific localization of antibodies in tumors have not been persuasive (1-4). This may have been due, in part, to problems associated with the specificity and homogeneity of the antibodies employed. Recent methods for the production of monoclonal antibodies in vitro (5, 6) now enable a more detailed examination of serologic approaches for the treatment of cancer. For example, radiographic imaging methods show that monoclonal antibodies
doi:10.4049/jimmunol.125.2.837
fatcat:pxm2bjmghzhlll36z6zosd2624