Document text
Machine-read from the scan, so expect some errors. Lines that couldn’t be read are left out.
Page 1
TISSUE SPECIFIC ANTIBODIES AS KSSIBLE THERAPEUTIC AGENIS FOR THE TREATMEXT OF CAmCER Radioactive isotopes w i l l be much more usef’ul i n the radiation therapy of cancer when means are developed for concentrating them i n tumor tissues as spec if fcd ly as inorganic radio-iodine will concentrate i n the human thyroid followiw intravenous radioactive isotope attached to an antibody that will be preferentially bound to same antigenic component associated with the tumor. gate the possible use of anti-tumor antibodies coupled with a radioactive isotope, as a therapeutic agent of this type. A possible tool in accomplishing this specific radiation effect may be a This project is designed t o investiAntisera, labeled with Il3l, have been prepared against normal rat tissues and several transplantable mouse and rat neoplasms and studied by s-i n vivo and a necessary step i n obtaining an antibody with a high specificity for binding i n tumor will be a preliminary separation of specific tumor-directed antibodies from those antibodies capable of reacting with both normal and tumor elements. separation is not carried out, antibodies t o stromal elements localize strongly also i n vascular normal organs, such 88 liver and adrenal. In general, the experimental work indicates that for most tumors Various’diverse methods are under investigation f o r preventing the production of antibodies common t o normal as well as malignant cells o r f o r removing tissues. These techniques include (1)the use of induced immunological tolerance, (2) the growth of tumor i n foreign species t o separate the neoplastic elements from the stromal elements; i.e., growth of mouse and human tumors i n rats, (3) the use of multiple specific absorptions of antisera w i t h cross-reacting tissues, and ( 4 ) the purification of antisera by multiple absorption-elution procedures using the tissue against which specific antibody is desired as the absorbing agent. For this purifi cation technique, two new reagents were discovered, urea and sodium salicylate, that act almost quantitatively i n breaking bonds between an insoluble antigen and an antibody, thus putting i n t o solution a major proportion of antibodies from such Since specific antibody localization i n cancer presumably occurs largely i n extravascular space, measurements were made of the rate a t which intravenously injected gamma globulin reaches the extravascular spaces of various rat organs and tissues, To differentiate between vascular and ext mm cula r space red cells labeled with radioactive chromium and gamma globulin Labeled with Ii31 w e r e used. The measurements indicate that in one hour about 5% of the gamma globulin i n the plasma entered the extravascular space of 1% of the body weight of l i v e r , kidney, and adrenal. Values for other tissues ranged from la5$ f o r lung and lymph node, 0.B for Walker carcinosarcoma 256 t o about 0.02qd for muscle and fat.