Other Therapeutic Monoclonal Antibodies

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Several other mAbs, targeting costimulatory molecules, adhesion molecules or cytokines, were tested in the past or are currently being investigated for the treatment of various autoimmune and inflammatory diseases, including MS (Table 13.1).

Recently dramatic and shocking problems occurred with a humanized superagonistic anti-CD28 monoclonal antibody (TeGenero, Wurzburg, Germany) in phase I. The anti-CD28 antibody directly activates reg

Table 13.1. Monoclonal antibodies tested in MS (adapted from Hohlfeld and Wekerle 2005) (further details about ongoing trials can be found at the website of the National MS Society USA: www.nationalmssociety.org/research.asp)

Antibody Therapeutic target Comments Study

Table 13.1. Monoclonal antibodies tested in MS (adapted from Hohlfeld and Wekerle 2005) (further details about ongoing trials can be found at the website of the National MS Society USA: www.nationalmssociety.org/research.asp)

Antibody Therapeutic target Comments Study

Natalizumab (Tysabri, formerly Antegren) (humanized)

4 integrin on leukocytes

Impressive clinical results in phase II and III; marketing suspended because of serious adverse reactions (PML)

Miller et al. (2003) and Polman et al. (2006)

Alemtuzumab (Campath-1H) (humanized)

CD52 on leukocytes

Long-lasting and sustained lymphocyte depletion; suppression ofMRI evidence of inflammation but not atrophy; induction of cytokine release; autoimmune thyroid disease

Coles et al. (1999); Moreau et al. (1994)

Daclizumab (humanized)

CD25 on activated cells

Promising in phase II

Bielekova et al. (2004)

Rituximab (mouse-human chimeric)

CD20 on B cells

Promising in neuromyelitis optica

Rizvi and Bashir (2004); Cree et al. (2005)

CNTO 1275 (fully human)

IL-12

Phase I/II

See web site of National MS Society USA

J695 (fully human)

IL-12

Phase I/II

See web site of National MS Society USA

IDEC-131 (humanized)

CD154 on immune cells and activated platelets

Phase I/II; clinical trials halted because ofthromboembolic complication

See web site of National MS Society USA

mAb monoclonal antibody, CSF cerebrospinal fluid, PML progressive multifocal leukoencephalopathy, IL-12 interleukin-12

mAb monoclonal antibody, CSF cerebrospinal fluid, PML progressive multifocal leukoencephalopathy, IL-12 interleukin-12

ulatory T cells (Fig. 13.1) (Luhder et al. 2003), and was extremely promising in models of MS, neuritis and experimental arthritis. Whilst to our knowledge no significant side effects occurred in any of the preceding animal experiments, including those with primates, or in vitro studies with human cells, all six healthy volunteers who were exposed to this antibody during a phase I study suffered from immediate, severe and life threatening allergic reactions which shocked people all over Europe (see news.bbc.co.uk/1/hi/england/london/ 4808836.stm). Fortunately the volunteers made almost a full recovery. The scientific and clinical investigations are still ongoing. One obvious consequence for future phase I trials is to administer novel agents sequentially, not simultaneously.

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Arthritis Joint Pain

Arthritis is a general term which is commonly associated with a number of painful conditions affecting the joints and bones. The term arthritis literally translates to joint inflammation.

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