Nav: Home

Mayo Clinic researchers identify potential immunotherapy drug combination

July 12, 2016

PHOENIX -- A drug combination designed to enhance the immune system's ability to zero in and attack cancer cells has shown a pronounced therapeutic effect against advanced and metastatic cancers in mice, according to a Mayo Clinic study, published in the July 12 edition of the online journal Oncotarget.

"Cancers can remain inconspicuous in the body for months to years before causing major problems, leading the immune system to coexist rather than to attack cancers," explains Mayo Clinic cancer immunotherapist Peter Cohen, M.D., who co-led the study with Mayo Clinic immunologist Sandra Gendler, Ph.D., and postdoctoral fellow Soraya Zorro Manrique, Ph.D.

"We tested Toll-like receptor (TLR) agonists -- drugs that mimic invasive bacteria -- as a strategy to trick the immune system into attacking cancer as if it were a life-threatening infection. Since chemotherapy can enhance immunotherapy, we also screened the pairing of TLR agonists with over 10 different chemotherapy agents," says Dr. Cohen, adding that the Mayo Clinic team targeted mouse models that included highly aggressive forms of breast cancer (known as 4T1) as well as pancreatic cancer (known as Panc02).

The investigative team observed that when the chemotherapy agent cyclophosphamide was combined with TLR agonists, advanced 4T1 and Panc02 cancers largely regressed within two cycles of treatment and did not recur if the mice completed five additional cycles of consolidating treatment. Only the combination of the TLR agonist and cyclophosphamide resulted in permanent cancer eradication, and no other tested chemotherapy came close to working as well as cyclophosphamide. The Mayo Clinic team also reported that the combined treatment was very well tolerated and actually less toxic than either TLR agonists or cyclophosphamide given individually.

Studies revealed that, even before treatment, the cancer-bearing mice had T-lymphocyte immune responses against their tumors, requiring only weekly injections of the TLR agonist and cyclophosphamide to become therapeutically effective. Importantly, the treatment agents did not need to be injected directly into tumors, and were fully effective against widespread metastases as well as the primary tumor sites.

The drug combination also revealed an additional benefit -- it activated monocytes (a type of white blood cell) to participate in the killing of cancer cells. Explains Dr. Gendler, "It appears very likely that each round of treatment stimulates the bone marrow to churn out freshly activated monocytes, which distribute throughout the body, spare normal cells, and find and kill cancer cells."

Dr. Cohen adds, "We were also able to identify TLR agonists that can similarly activate human monocytes to seek out and kill tumors."

Mayo Clinic is continuing its research, now studying within an FDA-approved clinical trial whether patients with advanced cancers, including pancreas, breast, colorectal, melanoma and others, respond similarly to mice when cyclophosphamide treatment is paired with the TLR agonist motolimod.
-end-
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

Mayo Clinic

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...