Development of a Fully Humanized Antibody for Treating Lung Emphysema

Project: Research project

Description

? DESCRIPTION (provided by applicant): Emphysema is a prevalent chronic obstructive pulmonary disease (COPD) induced predominantly by cigarette smoking is defined as the combination of chronic bronchitis (in the airways) and emphysema, which characterized by excessive cell apoptotic cell death of alveolar lung structural cells and chronic inflammation. Because alveolar structures are essential for gas exchange in the lungs, loss of this tissue component in emphysema affects life quality and health dramatically. Current COPD therapy targets mainly the airways, and no treatment is available for halting loss of parenchymal lung tissue. The founders of EmphyMAb have made the discovery that pro-apoptotic and monocyte stimulating cytokine endothelial monocyte activating protein (EMAPPI) is upregulated in the human bronchoalveolar lavage of current-smokers and of COPD patients who were ex-smokers. Enhanced levels of EMAPII in the murine lung can be experimentally induced by exposing mice to cigarette smoke (CS); furthermore, lung-specific transgenic overexpression of EMAPII causes emphysematous pathology in mouse lung. The strong correlation between disease pathology and EMAPII levels suggested modulating levels of this cytokine might be a useful therapeutic intervention in emphysema. To this end, the EmphMAb team developed an EMAPII specific neutralizing rat monoclonal antibody (mAB), which abrogated functional and morphometric manifestations of CS-induced emphysema in mice when administered either concomitantly or after prolonged CS exposure. The team succeeded in generation of a partially humanized chimeric antibody with only slightly less affinity and activity in comparison to the parental one. In this Phase I application, EmphyMAb and its partners at Indiana University plan to fully humanize and increase affinity of the MAb, and determine that the bioactivity and affinity
of this recombinant antibody are better or at least equivalent to the original MAb. The studies proposed here, will be the basis for future goals of establishing a highly specific fully humanized
EMAP II mAB for use in human COPD patients as a first treatment for halting the progressive loss of gas exchange permitting lung tissue.
StatusFinished
Effective start/end date9/1/152/29/16

Funding

  • National Institutes of Health: $175,753.00

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Antibodies, Monoclonal, Humanized
Emphysema
Lung
Chronic Obstructive Pulmonary Disease
Smoke
Tobacco Products
Monocytes
Gases
Monoclonal Antibodies
Pathology
Cytokines
Chronic Bronchitis
Bronchoalveolar Lavage
Therapeutics
Cell Death
Smoking
Quality of Life
Inflammation
Antibodies
Health

ASJC

  • Medicine(all)