Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers harness the immune system to improve stem cell transplant outcomes

02.10.2012
A novel therapy in the early stages of development at Virginia Commonwealth University Massey Cancer Center shows promise in providing lasting protection against the progression of multiple myeloma following a stem cell transplant by making the cancer cells easier targets for the immune system.

Outlined in the British Journal of Hematology, the Phase II clinical trial was led by Amir Toor, M.D., hematologist-oncologist in the Bone Marrow Transplant Program and research member of the Developmental Therapeutics program at VCU Massey Cancer Center. The multi-phased therapy first treats patients with a combination of the drugs azacitidine and lenalidomide.

Azacitidine forces the cancer cells to express proteins called cancer testis antigens (CTA) that immune system cells called T-cell lymphocytes recognize as foreign. The lenalidomide then boosts the production of T-cell lymphocytes. Using a process called autologous lymphocyte infusion (ALI), the T-cell lymphocytes are then extracted from the patient and given back to them after they undergo a stem cell transplant to restore the stem cells' normal function. Now able to recognize the cancer cells as foreign, the T-cell lymphocytes can potentially protect against a recurrence of multiple myeloma following the stem cell transplant.

"Every cell in the body expresses proteins on their surface that immune system cells scan like a barcode in order to determine whether the cells are normal or if they are foreign. Because multiple myeloma cells are spawned from bone marrow, immune system cells cannot distinguish them from normal healthy cells," says Toor. "Azacitidine essentially changes the barcode on the multiple myeloma cells, causing the immune system cells to attack them," says Toor.

The goal of the trial was to determine whether it was safe, and even possible, to administer the two drugs in combination with an ALI. In total, 14 patients successfully completed the investigational drug therapy. Thirteen of the participants successfully completed the investigational therapy and underwent a stem cell transplant. Four patients had a complete response, meaning no trace of multiple myeloma was detected, and five patients had a very good partial response in which the level of abnormal proteins in their blood decreased by 90 percent.

In order to determine whether the azacitidine caused an increased expression of CTA in the multiple myeloma cells, Toor collaborated with Masoud Manjili, D.V.M., Ph.D., assistant professor of microbiology and immunology at VCU Massey, to conduct laboratory analyses on bone marrow biopsies taken from trial participants before and after treatments. Each patient tested showed an over-expression of multiple CTA, indicating the treatment was successful at forcing the cancer cells to produce these "targets" for the immune system.

"We designed this therapy in a way that could be replicated, fairly inexpensively, at any facility equipped to perform a stem cell transplant," says Toor. "We plan to continue to explore the possibilities of immunotherapies in multiple myeloma patients in search for more effective therapies for this very hard-to-treat disease."

View a short video about this study featuring Toor and several patients who participated in the clinical trial:

In addition to Manjili, Toor collaborated with John McCarty, M.D., director of the Bone Marrow Transplant Program at VCU Massey, and Harold Chung, M.D., William Clark, M.D., Catherine Roberts, Ph.D., and Allison Hazlett, also all from Massey's Bone Marrow Transplant Program; Kyle Payne, Maciej Kmieciak, Ph.D., from Massey and the Department of Microbiology and Immunology at VCU School of Medicine; Roy Sabo, Ph.D., from VCU Department of Biostatistics and the Developmental Therapeutics program at Massey; and David Williams, M.D., Ph.D., from the Department of Pathology at VCU School of Medicine, co-director of the Tissue and Data Acquisition and Analysis Core and research member of the Developmental Therapeutics program at Massey.

The full manuscript of this study can be found online at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2012.09225.x/abstract;jsessionid=E1C7D245C01BA1228C06198A250BC990.d03t03

This research was supported, in part, with funding from VCU Massey Cancer Center's NIH-NCI Cancer Center Support Grant P30 CA016059.

John Wallace | EurekAlert!
Further information:
http://www.vcu.edu

More articles from Life Sciences:

nachricht Nerves control the body’s bacterial community
26.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Ageless ears? Elderly barn owls do not become hard of hearing
26.09.2017 | Carl von Ossietzky-Universität Oldenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The fastest light-driven current source

Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.

Graphene is up to the job

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

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...

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

Nerves control the body’s bacterial community

26.09.2017 | Life Sciences

Four elements make 2-D optical platform

26.09.2017 | Physics and Astronomy

Goodbye, login. Hello, heart scan

26.09.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>