BLOCKING LYMPHOMA INVASIVENESS WITH A MONOCLONAL-ANTIBODY DIRECTED AGAINST THE BETA-CHAIN OF THE LEUKOCYTE ADHESION MOLECULE (CD18)

The same integrin adhesion molecules used by normal leukocytes for tra ffic and localization in inflammation sites may be used by malignant c ells for dissemination. Identifying the adhesion molecules and then bl ocking them with appropriate antibody may therefore prove useful for c ontrolling tumor spread. This prediction was tested on a spontaneous m urine T cell lymphoma (LB) that expresses LFA-1 adhesion molecules. Th e adhesion molecules were identified by fluorocytometry and immunoprec ipitation with anti-CD18 mAb (M18/2). Subcutaneously inoculated LB lym phoma rapidly infiltrated the spleen and the lymph nodes, as indicated by histologic examination and [H-3]thymidine incorporation assay of p roliferating LB cells derived from the invaded organs. The normal orga nization of the lymphoid organs was totally effaced by the infiltratin g LB cells. Intravenous injection of anti-CD1 8 mAb, protein G-purifie d anti-CD18 mAb, or its F(ab')2 fragments (but not irrelevant control mAb) blocked the invasion of the s.c. inoculated lymphoma into the spl een. Whereas i.v. injected anti-CD18 mAb could not block the infiltrat ion of LB cells into the lymph nodes, local s.c. injection of this ant ibody near the lymph nodes partially inhibited lymphoma invasion into these organs. It was further found that LB cells form aggregates with spleen cells but not with lymph node cells. In addition, spleen-infilt rating LB cells invade both the spleen and the lymph nodes after s.c. injection. On the other hand, lymph node-infiltrating LB cells invade mainly the lymph nodes under similar circumstances.