Navigation Links
Moffitt Cancer Center researchers find potential key to new treatment for mantle cell lymphoma

Researchers at Moffitt Cancer Center and colleagues have demonstrated that the inhibition of signal transducer and activator of transcription 3 (STAT3) in mouse models of mantle cell lymphoma (MCL), an aggressive and incurable subtype of B-cell non-Hodgkin lymphoma that becomes resistant to treatment, can harness the immune system to eradicate residual malignant cells responsible for disease relapse.

Their study appears in a recent issue of Cancer Research, published by the American Association for Cancer Research.

"Despite good initial response to first-line treatment with chemotherapy and monoclonal antibodies, almost all patients with MCL will eventually relapse," said Eduardo M. Sotomayor, M.D., a senior member at Moffitt and the Susan and John Sykes Endowed Chair for Hematologic Malignancies. "MCL has one of the worst prognoses among all B-cell non-Hodgkin lymphomas."

Moffitt researchers and colleagues have exploited evidence that suggests the manipulation of the patient's own immune system might prove a good therapeutic strategy for patients with therapy-resistant MCL.

In a study using mouse models of MCL, the researchers hypothesized that targeting and inhibiting STAT3 a "negative regulator" of inflammatory responses in a variety of immune cells might "unleash an effective anti-lymphoma immune response."

According to Sotomayor, much of their work is in seeking new immunotherapeutic strategies capable of breaking tolerance to tumor antigens that is finding ways to defeat lymphoma cells' ability to resist treatment.

In this study, the researchers found that the inhibition of STAT3 in malignant B-cells, either by genetic manipulation or by using drugs (CPA-7 provided by Said M. Sebti, Ph.D., chair of the Drug Discovery Program at Moffitt and co-author of this study), render these cells "more visible" to specific immune cells (T-cells), which in turn can eradicate mantle cell lymphoma in murine models.

"The unique property of STAT3 inhibition to influence the inflammatory status of both malignant B-cells, as well as the antigen-presenting cells (as previously demonstrated by our group and others), points to pharmacologic inhibition of this signaling pathway as an appealing strategy to overcome tolerance to tumor antigens to elicit a strong anti-tumor immunity," concluded Sotomayor and his colleagues.

There have been other, similar attempts to induce an immune response, the authors noted. But these attempts offered effects that were "transient and not strong enough to fully eradicate systemic lymphoma." The authors speculated that the past limited success came from targeting either the malignant B-cell or the antigen-presenting cell, but not targeting both.

"It would be desirable to find approaches with the dual ability of enhancing the antigen-presenting function of malignant B-cells and inducing inflammatory antigen-presenting cells," Sotomayor said. "The inhibition of STAT3 signaling can do both. Therefore, STAT3 inhibition is an effective strategy in mouse models of MCL and provides a framework for future use of STAT3 inhibitors in combination with drugs that are capable of repairing defective immune responses in lymphoma patients."


Contact: Kim Polacek
H. Lee Moffitt Cancer Center & Research Institute

Related medicine news :

1. Moffitt Cancer Center study validates activity of rare genetic variant in glioma
2. Moffitt researchers find cutaneous human papillomavirus infection a risk factor for skin cancer
3. Moffitt Cancer Center researchers test drug combinations to prevent graft vs. host disease
4. Sun exposure and cutaneous HPV infection found synergistic in skin cancers, Moffitt says
5. Myelodysplastic syndrome treated with deferasirox shows beneficial iron reduction, Moffitt says
6. Moffitt researchers: Darwins principles say cancer will always evolve to resist treatment
7. Moffitt researcher, colleagues find success with new immune approach to fighting some cancers
8. Moffitt Cancer Center researchers develop and test new anti-cancer vaccine
9. Moffitt Cancer Center researchers identify drivers of sarcoma growth and survival
10. Researchers creating designer lymph nodes based on Moffitts Total Cancer Care initiative
11. Moffitt researcher awarded GE grant to develop tool to detect breast cancer metastasis genetic risks
Post Your Comments:
(Date:11/30/2015)... ... 30, 2015 , ... Holcomb – Kreithen Plastic Surgery ... practices in Florida, is proud to announce that Dr. Joshua Kreithen, one of ... Inc., a Johnson & Johnson Company. , Ethicon is a global medical device ...
(Date:11/30/2015)... ... November 30, 2015 , ... ... pleased to announce the speakers for “Value-Based Payer-Provider Partnerships: Three Case Studies,” ... three innovative value-based care arrangements: Essentia Health and UCare, MissionPoint Health Partners, ...
(Date:11/30/2015)... New York, New York (PRWEB) , ... November 30, 2015 , ... ... at the Greater New York Dental Meeting. Their Ecosystem empowers dentists to make complex ... Dentists who visit the booth will receive a free fee survey with 10 procedures ...
(Date:11/30/2015)... ... , ... The successful filing of an Investigational New Drug application (IND) is ... this key industry segment, Regis Technologies has decided to sponsor and participate in an ... EST. , Federal law does not allow new drugs to cross state lines until ...
(Date:11/30/2015)... ... 2015 , ... Vasont Systems, a top component content management ... unites with Syncro Soft’s latest software update, oXygen XML editor Version 17.1. Users ... latest release of oXygen® XML editor and the Vasont® CCMS. , The ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... Nov. 30, 2015   VolitionRx Limited (NYSE MKT: ... tests for a broad range of cancer types and other ... Micro Conference, which will be held December 1 - 3 in ... VolitionRx will be David Kratochvil , Chief Financial Officer ... Investor Relations. ® blood-based tests for colorectal ...
(Date:11/30/2015)... Nov. 30, 2015  Precision Image Analysis Inc. ... pleased to announce a dramatic expansion of its ... Building on its ISO-9001:2008 certification for its Quality ... Core Lab protocols and procedures. This expansion enables ... activities.  Their Core Lab services include design and ...
(Date:11/30/2015)... BOSTON , November 30, 2015 ... medicines directed at up to 10 G protein-coupled receptor ... PFE ) to research and develop potential new medicines ... targets across multiple therapeutic areas. --> Heptares ... development company and wholly-owned subsidiary of Sosei Group Corporation ...
Breaking Medicine Technology: