[Multibilly]

The return of interferon?

by Multibilly on Tue Sep 13, 2016 6:22 pm

It's only been tested in mouse models, but interesting nonetheless:

Pogue, SL, "Targeting Attenuated Interferon-α to Myeloma Cells with a CD38 Antibody Induces Potent Tumor Regression with Reduced Off-Target Activity," PLOS One, Sep 9, 2016 (full text of article)

Abstract:

Interferon-α (IFNα) has been prescribed to effectively treat multiple myeloma and other malignancies for decades. Its use has waned in recent years, however, due to sig­nifi­cant toxicity and a narrow therapeutic index (TI). We sought to improve IFNα’s TI by, first, attaching it to an anti-CD38 antibody, thereby directly targeting it to multiple myeloma cells, and, second, by intro­ducing an attenuating mutation into the IFNα portion of the fusion protein rendering it relatively inactive on normal, CD38 negative cells. This anti-CD38-IFNα(attenuated) immuno­cytokine, or CD38-Attenukine™, exhibits 10,000-fold increased specificity for CD38 positive cells in vitro compared to native IFNα and, significantly, is ~6,000-fold less toxic to normal bone marrow cells in vitro than native IFNα. Moreover, the attenuating mutation significantly de­creases IFNα biomarker activity in cynomolgus macaques indicating that this approach may yield a better safety profile in humans than native IFNα or a non-attenuated IFNα immuno­cytokine. In human xenograft multiple myeloma tumor models, anti-CD38-IFNα(attenuated) exerts potent anti-tumor activity in mice, inducing complete tumor regression in most cases. Furthermore, anti-CD38-IFNα(attenuated) is more efficacious than standard multiple myeloma treatments (lenalidomide, bortezomib, dexamethasone) and exhibits strong synergy with lenalidomide and with bortezomib in xenograft models. Our findings suggest that tumor-targeted attenuated cytokines such as IFNα can promote robust tumor killing while mini­mizing systemic toxicity.

[Wobbles]

Re: The return of interferon?

by Wobbles on Tue Sep 13, 2016 7:18 pm

Indeed!

Thanks for posting.

Joe