Efficacy and Metabolism of Azonafide Antibody-Drug Conjugates (ADCs) in Microgravity (ADCs in Microgravity) - 07.26.17

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
Efficacy and Metabolism of Azonafide Antibody-Drug Conjugates in Microgravity (ADCs in Microgravity) evaluates new antibody-drug conjugates (ADCs) from Oncolinx. These combine an immune-activating drug with antibodies and target only cancer cells, which increases the effectiveness of chemotherapy and reduces its side effects. In microgravity, cancer cells grow in three-dimensional, spheroid structures that closely resemble their form in the human body, allowing for better drug testing. This investigation accelerates development of targeted therapies for cancer patients.
Science Results for Everyone
Information Pending

The following content was provided by Luis Zea, Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: Antibody Conjugates

Principal Investigator(s)
Sourav Sinha, Oncolinx LLC, Boston, MA, United States

Co-Investigator(s)/Collaborator(s)
Dhaval Shah, Ph.D., Center for Translational Medicine, Schools of Pharmacy & Medicine, University at Buffalo, Buffalo, NY, United States
Riley Ennis, Oncolinx LLC, Boston, MA, United States

Developer(s)
BioServe Space Technologies, University of Colorado, Boulder, CO, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory (NL)

Research Benefits
Earth Benefits, Scientific Discovery

ISS Expedition Duration
April 2017 - September 2017; September 2017 - February 2018

Expeditions Assigned
51/52,53/54

Previous Missions
Information Pending

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Experiment Description

Research Overview

  • Efficacy and Metabolism of Azonafide Antibody-Drug Conjugates in Microgravity (ADCs in Microgravity) evaluates the molecular interactions and efficacy of Azonafide ADCs in cancer cells under conditions of microgravity.
  • This study will support drug metabolism studies that will compare concentration of Azonafide toxic payload within cancer cells to concentration of Azonafides in non-cancer cells to determine multiplier effect of ADC targeting.
  • These drug metabolism and efficacy studies give insight into how Azonafide ADCs behave in the human body.

Description

Targeting toxic therapeutics to tumors through receptors on the surface of cancer cells can reduce toxicity and increase effectiveness of the therapies, and Antibody-Drug Conjugates (ADCs) are a new class of biopharmaceuticals that do this. Oncolinx ADCs, armed with a novel cytotoxic payload developed at the National Cancer Institute (NCI), target and attack cancer cells and reduce the systemic toxicity that leads to adverse side effects commonly associated with chemotherapy. In addition, Azonafides activate immunogenic cell death, which initiates an anti-tumor immune response that should produce immunological memory to prevent disease recurrence. Oncolinx will test the efficacy and drug metabolism of Azonafide ADCs in microgravity cultures and, as such, accelerate the timeline to translational applications of the research. This company has been given exclusive access to these Azonafide ADCs from NCI, along with funding for related studies.
 
The Efficacy and Metabolism of Azonafide Antibody-Drug Conjugates in Microgravity (ADCs in Microgravity) experiment is integrated by BioServe Space Technologies at the University of Colorado, Boulder. The experiment is hosted in four MultiWell BioCells and two BioCell Habitats, and makes use of BioServe’s Space Automated Bioproduct Lab (SABL) and Atmosphere Control Module (ACM) to culture carcinoma (lung cells, Calu-3) at 37°C and 5% carbon dioxide (CO2).

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Applications

Space Applications
This research improves understanding of the differences in drug performance in microgravity and Earth environments. It also identifies specific changes caused by the microgravity environment and how those may influence drug performance. Such insights contribute to designing better drugs for cancer patients.

Earth Applications
Understanding the characteristics of antibody-drug conjugates (ADCs) informs future research and accelerates development of new cancer targets for these drugs. This study also provides insight into how Azonafide ADCs behave in the human body, advancing their use to treat people with cancer on Earth.

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Operations

Operational Requirements and Protocols

The cells are launched frozen and once in orbit, are thawed using BioServe’s Thawing System and introduced into the BioCells. n3D Biosciences’s nanoshuttles and magnets are used to manipulate fluid (e.g. introduction of the ADCs) in the wells while maintaining the cells in place and to better produce spherical cell clusters. Samples are fixed before analysis upon return to Earth. Hardware with samples is transported to International Space Station (ISS) under thermal control. Once the experiment reaches the ISS, the crew transfers the experiment from the cargo vehicle to the SABL unit that resides in the Expedite the Processing of Experiments to the Space Station (EXPRESS) rack on board the ISS. SABL is commanded to 37°C and 5% CO2 for incubation of the cells.

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Decadal Survey Recommendations

Information Pending

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Results/More Information

Information Pending

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Related Websites
Oncolinx, LLC Website

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Imagery

image
Azonafides are conjugated directly to tumor-targeting moieties called antibodies to deliver this immune-activating payload directly to the tumor. Once the Azonafide Antibody-Drug Conjugate (ADC) binds to the tumor surface, the construct is internalized by the tumor cells where the Azonafide is released and can initiate cell death. Azonafide ADCs enable local delivery of the drug to the tumor site, thereby avoiding the toxic side effects associated with systemic chemotherapy. Image courtesy of Oncolinx, LLC.

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