Monoclonal antibodies in the treatment of leukemia

MoAb-based therapies are evolving into the first broad-spectrum class of targeted anti-leukemic therapy. Developments in many areas, including computer modeling of receptors and ligands, and increasing sophistication in recombinant technologies may result in a rapid increase in the number and complexity of MoAb's available. We can anticipate an increase in the number of safer conjugates being delivered to leukemia cells. Further understanding of the in vitro mechanisms involved in tumor cell killing by MoAb will be important in maximizing the efficacy of this approach.     

Monoclonal antibodies to carbohydrate antigens in autologous bone marrow transplantation

Normal and malignant myeloid cells express a highly immunogenic oligosaccharide, lacto-n-fucopentaose-III (LNF-III), that has been identified by numerous monoclonal antibodies (MoAb). We have been interested in the use of a particular monoclonal antibody to LNF-III, PM-81, in the treatment of patients with acute myelogenous leukemia using the antibody to treat bone marrow in vitro. Following in vitro treatment of bone marrow with PM-81 and another MoAb, AML-2-23, the remaining cells are used as an autograft in a patient treated with high-dose chemotherapy and radiotherapy. In order to enhance the ability of the MoAb to lyse leukemic cells in the remission bone marrow, we have explored the effect of neuraminidase treatment on leukemia cells. In this paper we describe that myeloid leukemia cells expressing low levels of LNF-III by immunofluorescence can be shown to have high levels of LNF-III after neuraminidase treatment. In addition, we show that normal bone marrow progenitor cells do not have cryptic LNF-III antigen, thus allowing the application of this finding to the clinical setting. Moreover, we have shown that leukemia colony-forming cells from one patient with acute myelogenous leukemia express cryptic LNF-III and that after exposure to neuraminidase there was an increased ability of PM-81 in the presence of complement to eliminate these colony forming cells. These data indicate that the LNF-III moiety is almost universally expressed on myeloid leukemia cells and their progenitors but not expressed on normal progenitors. Thus, it may be possible to enhance leukemia cell kill in vitro by neuraminidase treatment of bone marrow.     

Detection of oxidized methionine in selected proteins, cellular extracts and blood serums by novel anti-methionine sulfoxide antibodies

Methionine sulfoxide (MetO) is a common posttranslational modification to proteins occurring in vivo. These modifications are prevalent when reactive oxygen species levels are increased. To enable the detection of MetO in pure and extracted proteins from various sources, we have developed novel antibodies that can recognize MetO-proteins. These antibodies are polyclonal antibodies raised against an oxidized methionine-rich zein protein (MetO-DZS18) that are shown to recognize methionine oxidation in pure proteins and mouse and yeast extracts. Furthermore, mouse serum albumin and immunoglobulin (IgG) were shown to accumulate MetO as function of age especially in serums of methionine sulfoxide reductase A knockout mice. Interestingly, high levels of methionine-oxidized IgG in serums of subjects diagnosed with Alzheimer’s disease were detected by western blot analysis using these antibodies. It is suggested that anti-MetO-DZS18 antibodies can be applied in the identification of proteins that undergo methionine oxidation under oxidative stress, aging, or disease state conditions.     

Time-conditioned coordination of dehydrogenase activity in blood cells in infantile acute leukemia.

The correlation of enzymatic activities studied at different periods of time (lasting from several hours to several days) has been revealed in 39 children at different stages of acute leukemia and in 8 children suffering from other hematological diseases (Hodgkin's disease, Morbus Werlhof, reactive reticulosis). The correlation of activity of enzymes constituting different systems and arranged in different parts of cell organelles enables us to explain this phenomenon by a regulation on a higher level, viz. cytophysiological processes as a whole. The coordination of enzymes possible depends on the synchronism of enzymatic activity caused by the physiological process developing in the cell.     

Thrombocytopenia after autologous bone marrow transplantation in in acute lymphatic leukemia]

There is reported about the treatment of refractory thrombocytopenia in a 9 years old boy following the autologous bone marrow transplantation for acute lymphoblastic leukaemia. The megakaryocytes were found diminished in the bone marrow smears. Controls of the thrombocyte count and the kinetics with radioactively labeled platelets of a donor spoke in favour of immunothrombocytopenia. Threatening bleeding complications challenged the use of all treatment possibilities. The irradiation of the spleen was without any success. After the splenectomy the thrombocyte count increased slowly, but after a remarkable lag phase, however. A diminished reproduction capacity of the bone marrow graft for special cell sorts has to be taken into account in such cases. The usual cytodynamics after splenectomy cannot be expected at all.     

Survey for vesicular stomatitis virus neutralizing antibodies in serums of white-tailed deer Odocoileus virginianus of the southeastern United States

New Jersey type vesicular stomatitis (VS) antibodies were found in 14 of 677 deer serums tested by neutralization tests in embryonated chicken eggs. Twelve positive serums were received from Louisiana and two from Georgia. Eight of the positive deer serums from Louisiana were collected in the area of the only reported case of VS during 1967. Clinical VS has not been diagnosed in the east coast states since 1964. Two positive deer serums were collected on Ossabaw Island, Georgia, and three positive serums, one each from a hog, bull, and sheep, were collected from young animals on the island. These findings indicated subclinical infection or a nidus of New Jersey VS in Georgia. The low percentage of New Jersey type VS antibodies in deer and the distribution parallel the low incidence of VS since 1964. No antibodies were present for Indiana type VS virus.     

In vitro autologous blast cell sensitization as immunotherapy in acute non-lymphocytic leukemia

Summary Remission mononuclear cells incubated in vitro for 96 h with autologous stored blast cells were reinfused IV on two occasions as adjuvant maintenance therapy. The procedures were well tolerated, but in vitro response to the blast cells was negligible.The present mean duration of complete remission (15.7 months) appears to be similar to that of 28 patients (12.4 months) treated at the same time with chemotherapy alone by the same physicians.