Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Creating a life-saving killer

16.08.2010
Cancer may be kept in check by a method for generating patient-specific immune cells with antitumor activity

Upon receiving the appropriate activating signal, natural killer T (NKT) cells live up to their name, releasing a torrent of molecules that trigger the protective immune response necessary to eliminate pathogens or even thwart tumor growth.

These cells represent a promising clinical tool, as demonstrated in a recent clinical trial in which lung cancer patients received NKT-stimulating injections of dendritic cells that had been pretreated with á-galactosylceramide (á-GalCer)1. Some 60% of treated patients exhibited a striking seven-fold improvement in their median survival time relative to their untreated counterparts. “The effects are superior to other molecular-targeted cancer drugs,” says Masaru Taniguchi of the RIKEN Research Center for Allergy and Immunology (RCAI), Yokohama, whose team participated in this study. “However, this therapy is not applicable to two-thirds of patients because of their limited number of NKT cells.”

To solve this problem, Taniguchi teamed up with RCAI colleague Haruhiko Koseki to develop a method for generating transplantable NKTs2. They derived these from induced pluripotent stem cells (iPSCs), embryonic-like cells that are typically generated via virus-mediated delivery of ‘reprogramming genes’ into skin cells. However, NKT maturation involves a complex genomic rearrangement event, making them difficult to derive from conventional iPSCs. As such, Taniguchi and Koseki devised a novel approach for generating mouse iPSCs from existing NKTs, which have already undergone this rearrangement. They used these iPSCs to generate large numbers of new NKTs in vitro.

Their method efficiently produced mature NKTs, which rapidly established a stable population within the liver upon transplantation into mice. To the researchers’ pleasant surprise, these new NKTs displayed typical activation behavior in response to á-GalCer-treated dendritic cells and proved capable of coordinating an effective immune response. “In general, cells generated from in vitro culture die quickly in vivo or are killed by host immune cells … however, this was not the case here,” says Taniguchi. “We detected iPSC-derived NKT cells with adjuvant activity and tumor-eradicating effects two weeks after cell transfer.”

Taniguchi, Koseki and colleagues are now keen to begin working with human cells. This transition will involve many new challenges, but the researchers see great clinical potential in their approach—particularly in the US, where the Food and Drug Administration has approved development of cell-based therapies. “NKT cell-targeted adjuvant cell therapy is applicable [to] any type of cancer patient, because it can overcome [their] immunodeficient status and enhances antitumor responses,” says Taniguchi. “At present, the delivery of patient dendritic cells is the main limiting factor.”

The corresponding author for this highlight is based at the Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology

Associated links

Link to article
Journal information
1. 1.Motohashi, S., Nagato, K., Kunii, N., Yamamoto, H., Yamasaki, K., Okita, K., Hanaoka, H., Shimizu, N., Suzuki, M., Yoshino, I., et al. A phase I-II study of alpha-galactosylceramide-pulsed IL-2/GM-CSF-cultured peripheral blood mononuclear cells in patients with advanced and recurrent non-small cell lung cancer. Journal of Immunology 182, 2492–2501 (2009).

2. 2.Watarai, H., Fujii, S., Yamada, D., Rybouchkin, A., Sakata, S., Nagata, Y., Iida-Kobayashi, M., Sekine-Kondo, E., Shimizu, K., Shozaki, Y. et al. Murine induced pluripotent stem cells can be derived from and differentiate into natural killer T cells. The Journal of Clinical Investigation 120, 2610–2618 (2010).

gro-pr | Research asia research news
Further information:
http://www.riken.jp
http://www.researchsea.com

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>