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!
Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex
New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences