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Mayo Clinic researchers identify therapy

March 08, 2017

PHOENIX -- Mayo Clinic researchers have found that an experimental drug, LCL161, stimulates the immune system, leading to tumor shrinkage in patients affected by multiple myeloma. The findings are published in Nature Medicine.

Multiple myeloma is a blood cancer that affects plasma cells - white blood cells that normally produce antibodies to fight infection. Rather than produce helpful antibodies, the cancer cells, as they grow, secrete large amounts of a single antibody that accumulate in the body, causing kidney problems and infections.

"The drug, LCL161, was initially developed to promote tumor death," says Marta Chesi, Ph.D., a Mayo Clinic biochemist and lead author of the study of 25 Multiple Myeloma patients. "However, we found that the drug does not kill tumor cells directly. Rather, it makes them more visible to the immune system that recognizes them as foreigner invaders and eliminates them."

Mayo Clinic researchers will conduct a follow-up clinical trial of LCL161 in combination with an inhibitor of immune checkpoints that has been widely used in many cancer treatments to evaluate if LCL161 could represent a potential new treatment option.

"The model for preclinical studies to predict with great accuracy which drugs would work in the clinic was developed a decade ago," says Dr. Chesi. "And it has been instrumental in the prioritization of which experimental therapeutics should be tested in patients with multiple myeloma."

The research highlights the importance of studying the effects of drugs not only on the tumor cells in a culture plate, but also on the interaction of the tumor cells with their own microenvironment. The finding that LCL161 is active against multiple myeloma suggests that similar drugs may have broader clinical activity than previously thought.
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The work of Dr. Chesi and her team reflects Mayo Clinic's focus to bridge basic science discoveries into clinical trials through collaboration, beginning with unmet patient needs.

Study co-authors are:
    * Ilseyar Akhmetzyanova, Albert Einstein College of Medicine
    * Gregory Ahmann, Mayo Clinic
    * Sikander Ailawadhi, M.D., Mayo Clinic
    * Yan Asmann, Ph.D., Mayo Clinic
    * Leif Bergsagel, M.D., Mayo Clinic, David F. and Margaret T. Grohne Professor of Novel Therapeutics for Cancer Research
    * Francis Buadi, M.D., Mayo Clinic
    * Arianna Calcinotto, Ph.D., Mayo Clinic Asher Chanan-Khan, M.D., Mayo Clinic
    * David Dingli, M.D., Ph.D., Mayo Clinic
    * Angela Dispenzieri, M.D., Mayo Clinic, Serene M. and Frances C. Durling Professor
    * Amylou Dueck, Ph.D., Mayo Clinic
    * Rafael Fonseca, M.D., Mayo Clinic, Getz Family Professor of Cancer
    * David Fooksman, Ph.D., Albert Einstein College of Medicine
    * Victoria Garbitt, Mayo Clinic
    * Morie Gertz, M.D., Mayo Clinic, Roland Seidler, Jr., Professor of the Art of Medicine in Honor of Michael D. Brennan, M.D.
    * Niamh Keane, M.B., Ch.B., Mayo Clinic Heidi Kosiorek, Mayo Clinic
    * Shaji Kumar, M.D., Mayo Clinic
    * Martha Lacy, M.D., Mayo Clinic
    * Yi Lin, M.D., Ph.D., Mayo Clinic
    * Kevin Morrison, Mayo Clinic
    * Noweeda Mirza, Ph.D., Mayo Clinic
    * Craig Reeder, M.D., Mayo Clinic
    * Daniel Riggs, Ph.D., Mayo Clinic
    * Meaghen Sharik, Mayo Clinic
    * Keith Stewart, M.D., Ch.B., Mayo Clinic, Vasek and Anna Maria Polak Professor of Cancer Research, Carlson and Nelson Endowed Director, Center for Individualized Medicine


About Mayo Clinic


Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. For more information, visit http://www.mayoclinic.org/about-mayo-clinic or http://newsnetwork.mayoclinic.org/.

Mayo Clinic

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