Preclinical efficacy and safety of pascolizumab (SB 240683): a humanized anti-interleukin-4 antibody with therapeutic potential in asthma

Clin Exp Immunol. 2002 Oct;130(1):93-100. doi: 10.1046/j.1365-2249.2002.01973.x.


The type 2 helper T cell (T(H)2) cytokine interleukin (IL)-4 is thought to play a central role in the early stages of asthma. In an effort to develop an antibody treatment for asthma that neutralizes the effects of IL-4, a murine monoclonal antibody, 3B9, was generated with specificity for human IL-4. In vitro studies demonstrated that 3B9 inhibited IL-4-dependent events including IL-5 synthesis, (T(H)2) cell activation and up-regulation of immunoglobulin E expression. 3B9 was then humanized (pascolizumab, SB 240683) to reduce immunogenicity in humans. SB 240683 demonstrated species specificity for both monkey and human IL-4 with no reactivity to mouse, rat, cow, goat or horse IL-4. Pascolizumab inhibited the response of human and monkey T cells to monkey IL-4 and effectively neutralized IL-4 bioactivity when tested against several IL-4-responsive human cell lines. Affinity studies demonstrated rapid IL-4 binding by pascolizumab with a slow dissociation rate. In vivo pharmacokinetic and chronic safety testing in cynomolgus monkeys demonstrated that pascolizumab was well tolerated, and no adverse clinical responses occurred after up to 9 months of treatment. Three monkeys developed an anti-idiotypic response that resulted in rapid pascolizumab clearance. However, in the chronic dosing study the antibody response was transient and not associated with clinical events. In conclusion, pascolizumab is a humanized anti-IL-4 monoclonal antibody that can inhibit upstream and downstream events associated with asthma, including (T(H)2) cell activation and immunoglobulin E production. Clinical trials are under way to test the clinical efficacy of pascolizumab for asthma.

MeSH terms

  • Animals
  • Anti-Asthmatic Agents / pharmacokinetics
  • Anti-Asthmatic Agents / therapeutic use*
  • Anti-Asthmatic Agents / toxicity
  • Antibodies, Anti-Idiotypic / biosynthesis
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal / toxicity
  • Antibody Specificity
  • Area Under Curve
  • Asthma / therapy*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Cattle
  • Cell Differentiation / drug effects
  • Cell Line / drug effects
  • Drug Evaluation, Preclinical
  • Epitopes / immunology
  • Female
  • Goats
  • Half-Life
  • Horses
  • Humans
  • Immunoglobulin E / biosynthesis
  • Immunotherapy*
  • Interleukin-4 / antagonists & inhibitors*
  • Interleukin-4 / immunology
  • Leukemia, Erythroblastic, Acute / pathology
  • Lymphocyte Activation / drug effects
  • Macaca fascicularis
  • Male
  • Mice
  • Organ Specificity
  • Safety
  • Spleen / cytology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Tumor Cells, Cultured / drug effects


  • Anti-Asthmatic Agents
  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Epitopes
  • Interleukin-4
  • Immunoglobulin E