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 Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

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: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

Hope to discover sure signs of life on Mars? New research says look for the element vanadium

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>