Evaluation of human anti-mouse antibody response in normal volunteers following repeated injections of fanolesomab (NeutroSpec), a murine anti–CD15 IgM monoclonal antibody for imaging infection

Line, Bruce R.; Breyer, Richard J.; McElvany, Karen D.; Earle, Dennis; Khazaeli, M. B.

doi:10.1097/01.mnm.0000134745.22032.49

Cited by 15 publications

(10 citation statements)

References 9 publications

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“…In contrast, the efforts have focused on using radiolabeled antimicrobial peptides, chemotactic cytokines, leukotriene b4 antagonists, bacteriophages, chitinase, and fluconazole to distinguish sterile inflammation from infection and fungal infections which are notoriously difficult to diagnose – from bacterial infections (8–13). In addition, the use of Fanolesomab (NeutroSpec), a murine IgM monoclonal antibody to CD15 labeled with 99m Tc that co-localizes with human polymorphonuclear neutrophils (PMNs) at the sites of infection was evaluated in healthy volunteers and in patients for imaging of infection and inflammation (14, 15). Here we will present the summary of the therapeutic efficacy of RIT of infections, its toxicity and radiobiological mechanisms as well as will outline future perspective for combining RIT of infections with modern imaging techniques such as SPECT and PET.…”

Section: Inroductionmentioning

confidence: 99%

Radioimmunotherapy of Infectious Diseases

Dadachova

Casadevall

2009

Seminars in Nuclear Medicine

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The need for novel approaches to treat infectious diseases is obvious and urgent. This situation has renewed interest in using monoclonal antibodies (mAbs) in therapy of infectious diseases. During the last 5 years radioimmunotherapy (RIT), a modality developed for cancer treatment, has been successfully adapted for the treatment of experimental fungal (C. neoformans and H. capsulatum), bacterial (S. pneumoniae and B. anthracis) and viral (HIV-1) infections. RIT produced none or only transient hematological toxicity in experimental animals. Investigation of radiobiological mechanisms of RIT of infections showed that microbial cells are killed by both "direct hit" and "crossfire" radiation. MAbs radiolabeled with either alpha-or beta-emitters stimulated apoptosis-like cell death, while only mAbs radiolabeled with alpha-emitter 213 Bi also decreased the metabolic activity of microbial cells. The success of this approach in laboratory studies combined with earlier nuclear medicine experience on pre-clinical and clinical studies utilizing radiolabeled organism-specific antibodies for imaging of infections provides encouragement for feasibility of therapeutically targeting microbes with labeled antibodies. We envision that first the organism-specific mAbs will be radiolabeled with imaging radionuclides such as 99m Tc or 111 In to localize the sites of infection with SPECT followed by RIT with 188 Re-or 90 Y-labeled mAb, respectively. Also, immunoPET might be utilized for imaging of infection before treatment if such positron-emitting radionuclides as 86 Y (matching pair for 90 Y) or 124 I (matching pair for 131 I) are available. It might be possible to create a so-called "pan-antibody" which would recognize an antigen shared by a particular class of human pathogens such as fungi, for example. The availability of such antibodies would eliminate the necessity of having antibodies specific for each particular microorganism and would enormously enhance the development of RIT of infectious diseases. INRODUCTIONThe need for novel approaches to treat infectious diseases is obvious and urgent. Currently available antibiotics have become less effective as microbes are increasingly developing resistance. In recent decades the problem has been compounded by the emergence of many new infectious diseases like HIV. Simultaneously the population of patients in whom current antimicrobial therapies are not effective because of their low immune status is expanding and *Author for correspondence: Department of Nuclear Medicine, 1695A Eastchester Road, Bronx, NY 10461 USA, Ph: 718-405-8485; FAX: 718-405-8457; E-mail: E-mail: edadacho@aecom.yu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors...

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Section: Inroductionmentioning

confidence: 99%

Radioimmunotherapy of Infectious Diseases

Dadachova

Casadevall

2009

Seminars in Nuclear Medicine

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“…99m Tc-fanolesumab is a murine anti-CD15 IgM monoclonal antibody labeled with 99m Tc which was approved for imaging of equivocal cases of acute appendicitis and was in trials for use in imaging osteomyelitis and occult infection (6,90,104,162 (90). Shortly after infusion, a transient drop in the absolute neutrophil number has been observed, but no infectious complications have been attributed to Tc-fanolesumab (102,104).…”

Section: Monoclonal Antibodies For Imagingmentioning

confidence: 99%

Infectious Complications Associated with Monoclonal Antibodies and Related Small Molecules

Salvaña

Salata

2009

Clin Microbiol Rev

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SUMMARY Biologics are increasingly becoming part of routine disease management. As more agents are developed, the challenge of keeping track of indications and side effects is growing. While biologics represent a milestone in targeted and specific therapy, they are not without drawbacks, and the judicious use of these “magic bullets” is essential if their full potential is to be realized. Infectious complications in particular are not an uncommon side effect of therapy, whether as a direct consequence of the agent or because of the underlying disease process. With this in mind, we have reviewed and summarized the risks of infection and the infectious disease-related complications for all FDA-approved monoclonal antibodies and some related small molecules, and we discuss the probable mechanisms involved in immunosuppression as well as recommendations for prophylaxis and treatment of specific disease entities.

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“…The use of a murine antigranulocyte antibody, however, has its own potential disadvantages including human antimurine antibody (HAMA) induction, as well as other adverse events. Preclinical trials indicated that fanolesomab was safe and that repeated injections of this agent at clinically useful doses did not appear to induce a strong HAMA response or to present a risk for serious adverse events [25,26]. Following its introduction, however, there were reports of several serious and life-threatening events, including two fatalities, shortly after fanolesomab administration.…”

Section: Discussionmentioning

confidence: 99%

Diagnosing prosthetic vascular graft infection with the antigranulocyte antibody 99mTc-fanolesomab

Tronco¹,

Love²,

Rini³

et al. 2007

Nuclear Medicine Communications

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Evaluation of human anti-mouse antibody response in normal volunteers following repeated injections of fanolesomab (NeutroSpec), a murine anti–CD15 IgM monoclonal antibody for imaging infection

Abstract: 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.

Cited by 15 publications

References 9 publications

Radioimmunotherapy of Infectious Diseases

Radioimmunotherapy of Infectious Diseases

Infectious Complications Associated with Monoclonal Antibodies and Related Small Molecules

Diagnosing prosthetic vascular graft infection with the antigranulocyte antibody 99mTc-fanolesomab

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