Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bioengineered soft microfibers improve T-cell production

18.01.2018

Columbia biomedical engineers design a new, biomaterials-based system that takes a soft approach to improving cell manufacturing and may bring new hope to cancer patients for T-cell therapy

T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, chemical-based approaches. These "living drugs" are poised to transform medicine, with a growing number of cellular therapies receiving FDA-approval.


Columbia biomedical engineers use soft fibers (red) to activate T cells (green), improving cellular immunotherapy.

Credit: Lance Kam/Columbia Engineering

A current bottleneck in these approaches and other Adoptive T-cell Therapies (ACTs) is the production of sufficient numbers of high quality T cells. As a starting material, cells are isolated from the patient and then modified and grown outside the body in a bioreactor.

This is still a new manufacturing challenge in medicine, and lack of a therapeutic number of cells is a frequent point of failure in ACT. In addition to technical challenges faced in consistent production of cells, T cells from patients undergoing treatment for cancer often show reduced function due to the disease, and are particularly difficult to grow.

A Columbia Engineering team has developed a new method for improving T-cell manufacture by focusing on the materials involved in this process. The team is a collaboration between Biomedical Engineering faculty Lance C. Kam and Helen H. Lu, whose research programs include immune engineering and smart biomaterial design. Their study, which is published today in Advanced Biosystems, uses a polymer mesh to activate the T cells, a critical step for their production. This approach simplifies processing compared to systems in use today. In addition, making the fibers out of a mechanically soft material improved T-cell growth, outperforming the current gold standard on several fronts.

"Our report shows that this soft mesh material increases the number of functional cells that can be produced in a single step," Kam says. "In fact, our system provided nearly an order of magnitude more cells in a single process. What's especially exciting is that we've been able to expand cells isolated from patients undergoing treatment for leukemia. These cells are often very difficult to activate and expand, and this has been a barrier to using cellular immunotherapy for the people who need it."

In testing the effect of a softer material on T-cell production, the team was inspired by the field of mechanobiology. Researchers have known that other cell types can sense the mechanical stiffness of a material. For example, the rigidity of a material used to culture stem cells can direct differentiation, with a softer material promoting production of neuron while a stiffer substrate encourages bone cell differentiation. This effect can be as strong as the chemicals normally used to direct differentiation. However, a similar effect was unexpected in T cells for activation.

"This makes sense for cells normally involved in force-related activities, like muscle cells or fibroblasts that are involved in wound closure and healing. Our group was one of the first to explore this possibility for T cells, which are not associated with such functions," Kam notes. These early experiments, involving his Microscale Biocomplexity Laboratory group, discovered that T-cells can sense the mechanical rigidity of the materials commonly used in the laboratory. To turn this into a clinically useful system, his group partnered with Lu's Biomaterials and Interface Tissue Engineering Laboratory to create a microfiber-based platform.

Beyond simplifying the process of cell expansion and improving T-cells expansion, Kam and Lu envision that the mesh platform will have applications beyond immunotherapy. They are refining their platform and exploring how T cells from cancer patients respond to their materials. Says Lu, "It is truly exciting to see how these bioinspired matrices can direct cell function and be successfully used for T-cell therapy."

###

About the Study

The study is titled "Enhanced activation and expansion of T cells using mechanically soft elastomer fibers."

Authors are: Alex Dang, Sarah De Leo, Danielle R. Bogdanowicz, Dennis J. Yuan, Helen H. Lu, and Lance C. Kam (Columbia Engineering); and Stacey M. Fernandes and Jennifer R. Brown (Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School).

The study was supported in part by the National Institutes of Health (AI110593 to L.C.K.), the National Science Foundation (through a GRFP to S.D. and A.P.D.), and the Columbia-Coulter Translational Research Partnership. J.R.B. has been supported by the Leukemia and Lymphoma Society (TRP# 6289-13) and the American Cancer Society (RSG-13-002-01-CCE), with the DFCI CLL Biorepository particularly supported by the Melton Family Fund for CLL Research, the Susan and Gary Rosenbach Fund for Lymphoma Research, and the Okonow Lipton Family Lymphoma Research Fund.

The authors declare no financial or other conflicts of interest.

LINKS:

Paper: https://doi.org/10.1002/adbi.201700167

DOI: 10.1002/adbi.201700167

http://www.adv-biosys.com

http://engineering.columbia.edu/

http://bme.columbia.edu/lance-c-kam

http://orion.bme.columbia.edu/~kam/

http://bme.columbia.edu/helen-h-lu

http://orion.bme.columbia.edu/lulab/

Columbia Engineering

Columbia Engineering, based in New York City, is one of the top engineering schools in the U.S. and one of the oldest in the nation. Also known as The Fu Foundation School of Engineering and Applied Science, the School expands knowledge and advances technology through the pioneering research of its more than 200 faculty, while educating undergraduate and graduate students in a collaborative environment to become leaders informed by a firm foundation in engineering. The School's faculty are at the center of the University's cross-disciplinary research, contributing to the Data Science Institute, Earth Institute, Zuckerman Mind Brain Behavior Institute, Precision Medicine Initiative, and the Columbia Nano Initiative. Guided by its strategic vision, "Columbia Engineering for Humanity," the School aims to translate ideas into innovations that foster a sustainable, healthy, secure, connected, and creative humanity.

Holly Evarts | EurekAlert!

Further reports about: Applied Science T-cell T-cell production fibroblasts muscle cells

More articles from Life Sciences:

nachricht Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides
16.07.2018 | Tokyo Institute of Technology

nachricht The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Subaru Telescope helps pinpoint origin of ultra-high energy neutrino

16.07.2018 | Physics and Astronomy

Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides

16.07.2018 | Life Sciences

New research calculates capacity of North American forests to sequester carbon

16.07.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>