Maryellen Feeney

A murine monoclonal antibody (OC125) has been developed that reacts with each of six epithelial ovarian carcinoma cell lines and with cryopreserved tumor tissue from 12 of 20 ovarian cancer patients. By contrast, the antibody does not bind to a variety of nonmalignant tissues, including adult and fetal ovary. OC125 reacts with only 1 of 14 cell lines derived from nonovarian neoplasms and has failed to react with cryostat sections from 12 nonovarian carcinomas.

Human leukemic cells which bear the common acute lymphoblastic leukemia antigen can be lysed with a murine monoclonal antibody (J-5) in the presence of rabbit complement. Conditions have been defined for eliminating 51Cr-labeled common acute lymphoblastic leukemia antigen-positive NALM-1 cells or cryopreserved leukemic lymphoblasts from a 100-fold excess of human bone marrow. Optimal lysis is obtained with treatment for a total of 90 min. Three treatments for 30 min are more effective than two treatments for 45 min or one treatment for 90 min. Separation of marrow on a Ficoll:diatrizoate gradient does not permit more effective elimination of leukemic cells. Tumor cell lysis is inhibited by high concentrations of common acute lymphoblastic leukemia antigen-positive cells (2 X 10(7)/ml) and by high concentrations of bone marrow (10(8)/ml). Under optimal conditions, greater than 99% of 51Cr-labeled leukemic lymphoblasts can be eliminated from a 100-fold excess of human marrow. Selective removal of leukemic cells from human bone marrow in vitro should facilitate trials of autologous marrow transplantation.

An animal model has been developed that utilizes antibody and complement to eliminate a transplantable cloned line of Wistar/Furth acute nonlymphocytic leukemia (CI-3) from syngeneic Wistar/Furth bone marrow. The CI-3 leukemia grows progressively from an i.v. inoculum of 10(1) to 10(2) cells. Antiserum has been raised in rabbits following multiple injections of CI-3. Using optimal concentrations of absorbed antibody and complement, approximately 3 logs of tumor could be destroyed in vitro, judged by the number of cells required to produce progressive growth in vivo. Similar incubation with antibody and complement did not affect the ability of Wistar-Furth marrow to reconstitute rats that had received lethal total-body irradiation (950 R). Each of the 33 irradiated rats that received mixtures of 10(4) CI-3 and 1.6 X 10(8) nucleated bone marrow cells succumbed to leukemia within 65 days, whereas 16 of 33 rats (48%) receiving similar inocula that had been treated with antibody and complement survived greater than 180 days without evidence of tumor growth. Repeated treatment of contaminated marrow with antibody and complement following removal of mature granulocytes and erythrocytes on density gradients permitted elimination of 10(5) CI-3.

Antisera were raised in New Zealand White rabbits against purified populations of murine ovarian carcinoma (MOT) cells that were freed from contaminating host leukocytes and erythrocytes. In contrast to other antisera raised against this tumor, heteroantisera from rabbits immunized with purified tumor cell suspensions consistently retained antitumor activity after exhaustive absorption with syngeneic (C3HeB/FeJ) adult and fetal tissues. Absorbed antisera inhibited tumor growth in vivo and reacted with MOT cells in vitro as judged by indirect immunofluorescence, binding of staphylococcal protein A, and complement-mediated cytotoxicity. Appropriately absorbed antisera failed to bind to fetal tissues or to adult spleen, ovary, and kidney cells. Antisera with similar specificity could be obtained with the use of populations purified on a fluorescence-activated cell sorter or on discontinuous rabbit serum albumin gradients. Optimal titers against tumor were raised with multiple injections of 5 x 10(5) gradient-purified MOT cells.