Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Football-shaped particles bolster the body's defense against cancer

14.10.2013
Researchers at Johns Hopkins have succeeded in making flattened, football-shaped artificial particles that impersonate immune cells.

These football-shaped particles seem to be better than the typical basketball-shaped particles at teaching immune cells to recognize and destroy cancer cells in mice.


T-cells (red) are activated more robustly when they interact with artificial antigen-presenting cells (green) that are elongated (right) versus round (left).

Credit: Karlo Perica

"The shape of the particles really seems to matter because the stretched, ellipsoidal particles we made performed much better than spherical ones in activating the immune system and reducing the animals' tumors," according to Jordan Green, Ph.D., assistant professor of biomedical engineering at the Johns Hopkins University School of Medicine and a collaborator on this work. A summary of the team's results was published online in the journal Biomaterials on Oct. 5.

According to Green, one of the greatest challenges in the field of cancer medicine is tracking down and killing tumor cells once they have metastasized and escaped from a tumor mass. One strategy has been to create tiny artificial capsules that stealthily carry toxic drugs throughout the body so that they can reach the escaped tumor cells. "Unfortunately, traditional chemotherapy drugs do not know healthy cells from tumor cells, but immune system cells recognize this difference. We wanted to enhance the natural ability of T-cells to find and attack tumor cells," says Jonathan Schneck, M.D., Ph.D., professor of pathology, medicine and oncology.

In their experiments, Schneck and Green's interdisciplinary team exploited the well-known immune system interaction between antigen-presenting cells (APC) and T-cells. APCs "swallow" invaders and then display on their surfaces chewed-up protein pieces from the invaders along with molecular "danger signals." When circulating T-cells interact with APCs, they learn that those proteins come from an enemy, so that if the T-cells see those proteins again, they divide rapidly to create an army that attacks and kills the invaders.

According to Schneck, to enhance this natural process, several laboratories, including his own, have made various types of "artificial APCs" — tiny inanimate spheres "decorated" with pieces of tumor proteins and danger signals. These are then often used in immunotherapy techniques in which immune cells are collected from a cancer patient and mixed with the artificial APCs. When they interact with the patient's T-cells, the T-cells are activated, learn to recognize the tumor cell proteins and multiply over the course of several days. The immune cells can then be transferred back into the patient to seek out and kill cancer cells.

The cell-based technique has had only limited success and involves risks due to growing the cells outside the body, Green says. These downsides sparked interest in the team to improve the technique by making biodegradable artificial APCs that could be administered directly into a potential patient and that would better mimic the interactions of natural APCs with T-cells. "When immune cells in the body come in contact, they're not doing so like two billiard balls that just touch ever so slightly," explains Green. "Contact between two cells involves a significant overlapping surface area. We thought that if we could flatten the particles, they might mimic this interaction better than spheres and activate the T-cells more effectively."

To flatten the particles, two M.D./Ph.D. students, Joel Sunshine and Karlo Perica, figured out how to embed a regular batch of spherical particles in a thin layer of a glue-like compound. When they heated the resulting sheet of particles, it stretched like taffy, turning the round spheres into tiny football shapes. Once cooled, the film could be dissolved to free each of the microscopic particles that could then be outfitted with the tumor proteins and danger signals. When they compared typical spherical and football-shaped particles — both coated with tumor proteins and danger signals at equivalent densities and mixed with T-cells in the laboratory — the T-cells multiplied many more times in response to the stretched particles than to spherical ones. In fact, by stretching the original spheres to varying degrees, they found that, up to a point, they could increase the multiplication of the T-cells just by lengthening the "footballs."

When the particles were injected into mice with skin cancer, the T-cells that interacted with the elongated artificial APCs, versus spherical ones, were also more successful at killing tumor cells. Schneck says that tumors in mice that were treated with round particles reduced tumor growth by half, while elongated particles reduced tumor growth by three-quarters. Even better, he says, over the course of a one-month trial, 25 percent of the mice with skin cancer being treated with elongated particles survived, while none of the mice in the other treatment groups did.

According to Green, "This adds an entirely new dimension to studying cellular interactions and developing new artificial APCs. Now that we know that shape matters, scientists and engineers can add this parameter to their studies," says Green. Schneck notes, "This project is a great example of how interdisciplinary science by two different groups, in this case one from biomedical engineering and another from pathology, can change our entire approach to tackling a problem. We're now continuing our work together to tweak other characteristics of the artificial APCs so that we can optimize their ability to activate T-cells inside the body."

This work was supported by grants from the Johns Hopkins University Institute for NanoBioTechnology, the National Institute of Allergy and Infectious Diseases (AI072677, AI44129), the National Cancer Institute (CA108835) and the National Institute of Biomedical Imaging and Bioengineering (EB016721).

On the Web:

Link to article: http://dx.doi.org/10.1016/j.biomaterials.2013.09.050

Schneck Lab: http://pathology.jhu.edu/schnecklab/index.cfm

Green Lab: http://www.bme.jhu.edu/people/primary.php?id=876

Media Contacts: Catherine Kolf; 443-287-2251; ckolf@jhmi.edu
Vanessa McMains; 410-502-9410; vmcmain1@jhmi.edu
Shawna Williams; 410-955-8236; shawna@jhmi.edu

Catherine Kolf | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)

nachricht Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>