lewis-x-antigen and Infections

99mTc-fanolesomab is a radiolabeled imaging agent which is being developed by Palatin Technologies for use in the diagnosis of various infections, including appendicitis and osteomyelitis.

Topics: Animals; Antibodies, Monoclonal; Clinical Trials as Topic; Humans; Infections; Injections, Intravenous; Lewis X Antigen; Radiopharmaceuticals; Structure-Activity Relationship; Technetium

Fanolesomab (NeutroSpec) is a murine monoclonal Tc labelled anti-CD15 IgM antibody that localizes collections of human polymorphonuclear neutrophils (PMNs) at sites of infection.. The objectives of this study were to evaluate the safety of repeated injections of fanolesomab and the extent of induction of human anti-mouse antibody (HAMA) response.. Thirty healthy adults (15 men and 15 women) were enrolled in the study. Subjects were injected on two separate occasions, separated by 21 days, with 125 microg of fanolesomab that had been labelled with decayed Tc. HAMA assays were performed on blood samples drawn prior to each injection, and at 7 and 28 days following the second injection. Safety was determined by monitoring for adverse events, and for changes in vital signs, physical examination and clinical laboratory measurements.. Five subjects exhibited induction of HAMA (16.7%; 95% CI, 6.3-34.2%). Two were considered marginal responses (increase from 5 to 31, and 5 to 20 and 24 ng x ml), and three were considered moderate (7 to 228, 7 to 140 and 270, and 7 to 35 and 450 ng x ml). There were no strong responses (greater than 1000 ng x ml). Seven subjects experienced adverse events, most of which were coincidental to administration of fanolesomab. There were no serious or severe adverse events.. Repeated fanolesomab injections at clinically useful doses does not appear to induce a strong HAMA response nor does it present a risk for serious adverse events.

Topics: Adult; Animals; Antibodies, Monoclonal; Dose-Response Relationship, Drug; Female; Humans; Immunoglobulin M; Infections; Injections, Intravenous; Lewis X Antigen; Male; Mice; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Reference Values; Risk Assessment; Risk Factors

LeuTech is a 99Tcm labelled, anti-CD15, IgM, murine monoclonal antibody shown to have high affinity (Kd = 10(-11) M) for CD15 receptors (5.1 x 10(5)/cell) expressed on human neutrophils. LeuTech was injected directly, intravenously, and its efficacy in imaging infection in 46 consecutive patients was determined. Human anti-mouse antibody (HAMA) response was examined in 30 normal volunteers using a standard LeuTech dose reconstituted with decayed 99Tcm solution. There were 38 true positive, six true negative, and two false negative scans. Of the 38 positive images, 33 (92%) were positive within 10 min after injection of LeuTech. LeuTech accuracy in this group of patients was 96%, sensitivity 95%, specificity 100%, positive predictive value (PPV) 100%, and negative predictive value (NPV) 75%. No elevation of the HAMA titre was observed in any of the 30 normal volunteers and no adverse reaction was noted in any patient. LeuTech is a highly promising agent for rapid imaging of infectious foci.

Topics: Adult; Animals; Antibodies, Monoclonal; Appendicitis; Bone Diseases; False Negative Reactions; Female; Humans; Infections; Lewis X Antigen; Lung Diseases; Male; Mice; Middle Aged; Predictive Value of Tests; Radiopharmaceuticals; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

The cell surface phenotype of leukocyte subsets during reconstitution following autologous bone marrow transplantation (ABMT) using bone marrow purged with anti-myeloid monoclonal antibodies (MoAbs) and complement (C') was evaluated in 20 patients with acute myeloid leukemia (AML). Repopulation of B and T lymphocytes, natural killer (NK) cells, and myeloid cells was assessed by phenotypic analysis using two-color cytofluorography of peripheral blood mononuclear cells (PBMNC) at several time points up to 2 years post-transplantation. In spite of removal of the majority of monomyeloid cells of the autograft by purging with anti-CD14 and anti-CD 15, engraftment occurred rapidly. The myeloid cells appeared normal by surface phenotype. An early rise in NK cells, characterized by expression of CD57 and CD 16, was seen. The CD4:CD8 ratio remained low throughout the study period, primarily due to a persistently low CD4 level. ABMT using bone marrow purged with the anti-myeloid MoAbs PM-81 and AML-2-23 and C' resulted in prompt engraftment of neutrophils. Although there was a prolonged time for recovery of lymphocyte subsets, this did not result in an increased risk of early infectious complications. Late infectious complications post-transplantation were limited to herpes zoster infection in one patient 18 months post-transplantation, and bacterial meningitis in that same patient 2 months later. This study demonstrates that ABMT in patients with AML using bone marrow purged with the anti-myeloid MoAbs PM81 (anti-CD15) and AML-2-23 (anti-CD14) and C' results in rapid hematologic engraftment and delayed phenotypic immunologic reconstitution without significant acute or chronic clinical toxicities.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bone Marrow Purging; Bone Marrow Transplantation; Female; Follow-Up Studies; Graft Survival; Humans; Immunophenotyping; Infections; Leukemia, Myeloid, Acute; Lewis X Antigen; Lipopolysaccharide Receptors; Lymphocyte Subsets; Male; Middle Aged; Transplantation, Autologous