A new paradigm for antibody-directed conjugates

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43CA159720-01
Agency Tracking Number: R43CA159720
Amount: $199,122.00
Phase: Phase I
Program: SBIR
Awards Year: 2011
Solicitation Year: 2011
Solicitation Topic Code: NCI
Solicitation Number: PA10-050
Small Business Information
802 Deming Way, MADISON, WI, 53717-
DUNS: 787342471
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (608) 836-0207
Business Contact
Phone: (608) 836-0207
Email: prudent@centrosepharma.com
Research Institution
DESCRIPTION (provided by applicant): Non-small cell lung cancer (NSCLC) is among the most common and lethal cancers yet, the current standard of care for advanced stage NSCLC provides only modest improvements in overall survival or quality of life. Thus,there exists a significant unmet need for new effective therapies to treat NSCLC. Herein we describe an innovative new type of antibody drug conjugate (ADC) to target NSCLC. The core innovation of the proposed ADC derives from the use of a stable covalentlinker between the drug cargo (a novel steroidal glycoside) and the cancer-targeting mAb (anti-FXYD5), both of which act upon the extracellular face of the cancer cell. This elegantly simple design eliminates the need for ADC internalization or engineereddrug cargo release (the two major liabilities of existing ADCs) and thereby offers a paradigm shift in ADC technology. While the phase I studies described herein are focused upon NSCLC as the model, it is anticipated the novel ADC described herein will beequally effective for the treatment of other difficult cancers. Furthermore, since there exist many other suitable extracellular antigen/drug targets toward which this concept could be applied, success of the proof of concept studies described herein couldopen the door to an array of new promising ADCs. PUBLIC HEALTH RELEVANCE: We propose to develop the first cancer-targeted antibody-drug conjugate (ADC) that does not require either internalization or engineered drug release. This ADC presents a paradigm shift in ADC technology and is thereby anticipated to transform the future development of targeted therapies to treat cancer.

* Information listed above is at the time of submission. *

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