Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeted immunotherapy eradicates cancer in mice

10.02.2003


May have potential value in treating patients with hematologic cancers



Researchers have developed a novel approach to genetically instruct human immune cells to recognize and kill cancer cells in a mouse model. The investigators plan to ultimately apply this strategy in a clinical trial setting for patients with certain forms of leukemias and lymphomas.

Scientists at Memorial Sloan-Kettering Cancer Center (MSKCC) genetically engineered an antigen receptor, introduced it into cultured human T cells, and infused the T cells in mice that bear widespread tumor cells. The modified T cells, now able to recognize the targeted antigen present on the tumor cells, eradicated the cancer.


The research will be published in the March 2003 issue of Nature Medicine and will be available on the journal’s Web site on February 10. It is the first time that adoptive immunotherapy with engineered human T cells has demonstrated in vivo efficacy in mice.

"Our findings represent a step forward in the field of adoptive T cell therapy," said senior author Michel Sadelain, MD, PhD, Head of the Gene Transfer and Gene Expression Laboratory and Co-Director of the Gene Transfer and Somatic Cell Engineering Laboratory at MSKCC. "Our studies aim to better understand the biological needs of T cells that are targeted to tumors and may potentially be applied to a variety of cancers in the foreseeable future."

Earlier experiments have shown that genetically modified human T cells could kill tumor cells in vitro, but the cells could not successfully carry out other immunological responses such as maintaining cell division, and would die prematurely when they were infused into the body of a mouse. In this study, researchers may have overcome some of these limitations by designing a method whereby human T cells, genetically altered to recognize certain blood cancers, multiply in such a manner that they retain the ability to eliminate human tumors in vivo in mice.

Investigators genetically instructed the T cells to target cells that express CD19, a protein found on the surface of normal and cancerous B cells, a type of white blood cell. B cell cancers include acute lymphoblastic leukemias (ALL), chronic lymphocytic leukemias (CLL), and most non-Hodgkin’s lymphomas.

"This unique methodology enables us to expand the number of specific T cells to clinically relevant numbers and extend their viability, thereby enhancing their therapeutic effectiveness and enabling them to eradicate disease, in this case a B cell tumor," said Dr. Sadelain.

The researchers also tested the genetically modified human T cells (or lymphocytes) in vivo. They established a mouse model in which human tumors are disseminated throughout the body and administered the T cells intravenously. In collaboration with nuclear medicine experts at MSKCC, the scientists used molecular imaging (Positron Emission Tomography or PET scanning) to map out exactly where the tumor cells were in the mice and to track the effectiveness of the therapy.

In addition, researchers were able to show that T cells obtained from patients with advanced CLL could be targeted in this manner to efficiently kill their own tumor cells in vitro.

"Collectively, these findings show that we have met many of the criteria necessary to conduct a clinical trial and test this approach in humans," said lead author Renier Brentjens, MD, PhD, an attending medical oncologist on the Leukemia Service at MSKCC and a member of Dr. Sadelain’s laboratory. "This field holds a lot of promise and we are currently investigating other genes to try to make T cells more robust in mounting immune responses against tumor cells," said Isabelle Rivière, PhD, Co-Director of the Gene Transfer and Somatic Cell Engineering Laboratory at MSKCC and a co-author of the study.


This study was supported by the National Institutes of Health; the MSKCC Department of Medicine Translational and Integrative Medicine Fund; The Goodwin Experimental Therapeutics Center (ETC) Fund at MSKCC; The Cure for Lymphoma Foundation (now called the Lymphoma Research Foundation); and Golfers Against Cancer.

Memorial Sloan-Kettering Cancer Center is the world’s oldest and largest institution devoted to prevention, patient care, research and education in cancer. Our scientists and clinicians generate innovative approaches to better understand, diagnose and treat cancer. Our specialists are leaders in biomedical research and in translating the latest research to advance the standard of cancer care worldwide.

Esther Carver | EurekAlert!
Further information:
http://www.mskcc.org/

More articles from Health and Medicine:

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

nachricht The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

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

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>