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BRAF-targeted therapy with immunotherapy boosts T-cell recognition without affecting function

-- Beth Gilbert

Wednesday, June 16, 2010 (Last Updated: 06/17/2010)

WEDNESDAY, June 16 (HealthDay News) -- A novel approach using targeted therapy against the BRAF/mitogen-activated protein kinase (MAPK) pathway in combination with immunotherapy holds promise in the treatment of melanoma, according to a preclinical study published online June 15 in Cancer Research.

Andrea Boni, M.D., of the Massachusetts General Hospital in Boston, and colleagues used biopsies of melanoma tumors to examine the effects of MAPK pathway inhibition compared to selective inhibition of BRAFV600E on T-cell function.

The researchers found that inhibiting the MAPK pathway with a specific inhibitor of BRAFV600E or MAPK/extracellular signal-regulated kinase kinase (MEK) inhibitors in melanoma cell lines and tumor digests increases levels of melanocyte differentiation antigens (MDAs), which is associated with improved recognition of antigen-specific T lymphocytes. However, the researchers found that treatment with MEK inhibitors impaired T lymphocyte function, while function was preserved after treatment with a specific inhibitor of BRAFV600E.

"These findings suggest that immune evasion of melanomas mediated by oncogenic BRAF may be reversed by targeted BRAF inhibition without compromising T-cell function," the authors write. "These findings have important implications for combined kinase-targeted therapy plus immunotherapy for melanoma."

One author disclosed serving on an advisory board for Roche Pharmaceuticals.

Abstract
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Specialties Hematology & Oncology
Dermatology
Pathology

Copyright © 2010 HealthDay. All rights reserved.


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