Microgravity Growth of Crystalline Monoclonal Antibodies for Pharmaceutical Applications (CASIS PCG 5) - 02.22.17

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

ISS Science for Everyone

Science Objectives for Everyone
Monoclonal antibodies are molecules designed to attach to certain molecules in the body, and they are important for fighting a wide range of human diseases, including cancer. The Microgravity Growth of Crystalline Monoclonal Antibodies for Pharmaceutical Applications (CASIS-PCG-5) investigation crystallizes a monoclonal antibody developed by Merck Research Labs. Microgravity enables the growth of extremely high-quality crystals, which allow scientists to study the proteins’ structure, improve drug delivery, manufacturing, and developing better methods for storing these biological molecules.
Science Results for Everyone
Information Pending

The following content was provided by Paul Reichert, M.S., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom:

Principal Investigator(s)
Paul Reichert, M.S., Merck Research Laboratories, Kenilworth, NJ, United States

Co-Investigator(s)/Collaborator(s)
Information Pending

Developer(s)
Center for the Advancement of Science in Space (CASIS), Rockledge, FL, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory (NL)

Research Benefits
Space Exploration, Earth Benefits, Scientific Discovery

ISS Expedition Duration
September 2015 - March 2016; March 2016 - April 2017

Expeditions Assigned
45/46,47/48,49/50

Previous Missions
Space Shuttle Missions STS-51, 52, 53, 62, 66, 68, 70, 95, 101, 107, and 110 as well as three ISS flights: ISS-8A, ISS Increment 39/40, and ISS Increment 43/44.

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Experiment Description

Research Overview
To date, earth grown crystalline suspensions of monoclonal antibodies have not been of high enough quality to fully model using X-ray crystallography. With the absence of gravity and convection on the ISS, larger crystals with purer compositions and structures can be grown. In the Microgravity Growth of Crystalline Monoclonal Antibodies for Pharmaceutical Applications (CASIS PCG-5) investigation, single X-ray diffraction quality crystals are to be grown, inspected, and characterized by similar traits. Crystalline suspensions are analyzed using a battery of bio-physical methods to characterize the purity, biological activity, and size distribution for multiple pharmaceutical applications.

Description

The growth of crystals that diffract to higher resolution could be the difference between getting interpretable and un-interpretable data, leading to finding a better high resolution structure. Structural information could help in the understanding of the functional parts of monoclonal antibodies, such as epitope binding, and help envision the design of new and improved monoclonal antibodies.
 
The Microgravity Growth of Crystalline Monoclonal Antibodies for Pharmaceutical Applications (CASIS PCG-5) investigation uses few resources, and has a flexible strategy that makes it an ideal system for ISS. The CASIS PCG-5 hardware launches in a Double Cold Bag at +4°C to prevent crystal formation prior to reaching microgravity. The experiment samples in the Handheld HDPCG hardware are activated by turning the sample cells 90 degrees clockwise to introduce the sample insert to the precipitant reservoir. The experiment samples in the Handheld PCF hardware are activated by elevated temperatures. Following the Handheld HDPCG activation, all three hardware assemblies are transferred to MERLIN. The temperature in MERLIN begins at +4°C, and ramps up to +30°C over a period of 48 hours. Following approximately 18 days of crystal growth, all assemblies are removed from MERLIN. The Handheld HDPCG experiment samples are deactivated by turning the sample cells 180 degrees clockwise. This operation turns the protein insert opposite of the precipitant reservoir and stops the experiment. All hardware assemblies return at ambient temperature in a soft stowage bag.

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Applications

Space Applications
Scientists crystallize proteins to glimpse visualize how biological molecules are arranged, which can provide new information about how they work in the body. This investigation crystallizes a monoclonal antibody currently in clinical trials for treating various human diseases. The investigation depends on the microgravity environment of the ISS, where gravity and convection do not interfere with crystallization as they would on Earth. The investigation also builds on previous research obtained on earlier flight experiments, testing scientists’ hypotheses and using the ISS as a long-term scientific platform.

Earth Applications
The monoclonal antibodies used in this investigation are currently being tested for treatment of several human diseases. Crystallizing the protein allows scientists to understand how it functions, and potentially improves treatment for patients on Earth. Crystallizing monoclonal antibodies could enable a method for delivering large doses with injections rather than intravenously, and improves methods for storing monoclonal antibodies for extended periods. Improving drug delivery and design benefits patients on Earth suffering from a wide range of diseases.

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Operations

Operational Requirements and Protocols

Time between payload turnover and launch is 24 hours. While On-orbit: experiment should be placed in refrigerated stowage prior to transfer to MERLIN; sample activation must be completed within six days following launch; sample removal and deactivation can occur as soon as 18 days after MERLIN installation.
 
Experiment is to be returned to Earth under ambient conditions: temperature cannot fall below 10°C; early recovery at the shipping dock is required. Samples are shipped to a laboratory for X-ray crystallography characterization.

One Handheld HDPCG and three Handheld PCF assemblies are transferred from cold stowage on the ascent vehicle, to the ISS. To activate the experiment samples in the Handheld HDPCG hardware, an Activation Tool (which is attached to the side of the HDPCG hardware using Velcro) is removed and attached to each of the five cell blocks. Each cell block is turned 90 degrees clockwise to align the sample insert with the precipitant solution. Experiment samples in the Handheld PCF hardware are activated by elevated temperatures. Following Handheld HDPCG activation, all hardware assemblies are transferred to MERLIN. MERLIN provides a temperature ramp up from +4°C to +30°C over a 48 hour period. Crystals grow in MERLIN for approximately 18 days, and then all three hardware assemblies are removed from MERLIN. The Handheld HDPCG experiment samples are deactivated by attaching the Activation Tool to each cell block and turning 180 degrees clockwise to turn the protein insert opposite of the precipitant reservoir. The Handheld PCF experiment samples are deactivated when exposed to temperatures below 28°C. Prior to unberth, all hardware assemblies are transferred to ambient stowage on the descent vehicle for return.
 

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Decadal Survey Recommendations

Information Pending

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Results/More Information

Information Pending

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Related Websites

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Imagery