Prabhala, Rao, Munschi, Nikhil, Ettenberg, Seth and Di Padova, Franco E. (2016) Targeting IL-17A in Multiple Myeloma: 2 A Potential Novel Therapeutic Approach in Myeloma. 3 (Running title: Th17 pathway in myeloma) 4. Leukemia.

Abstract

We have previously demonstrated that interleukin-17A (IL-17) producing Th17 cells are
3 significantly elevated in blood and bone marrow (BM) in multiple myeloma (MM) and IL-
4 17A promotes MM cell growth via the expression of IL-17 receptor. In this study, we
5 evaluated anti-human IL-17A human monoclonal antibody (mAb), AIN457 in MM. We
6 observe significant inhibition of MM cell growth by AIN457 both in the presence and
7 absence of BM stromal cells (BMSC). While IL-17A induces IL-6 production, AIN457
8 significantly down-regulated IL-6 production and MM cell-adhesion in MM-BMSC co
9 culture. AIN-457 also significantly inhibited TRAP+ multi-nucleated osteoclast cell–
10 differentiation. In the sub-cutaneous MM xenograft model, we observed significant
11 reduction in tumor volume by pre-treatment with AIN457 compared to isotype control.
12 More importantly, in the SCIDhu model of human myeloma where MM cells grow within
13 the human microenvironment, administration of AIN-457 weekly for 4 weeks after the
14 first detection of tumor in mice led to a significant inhibition of tumor growth as well as
15 reduced bone damage compared to isotype control mice. These pre-clinical in vitro and
16 in vivo observations suggest efficacy of AIN 457, anti-IL-17A human mAb in myeloma
17 and provide the rationale for its clinical evaluation both for anti-myeloma effects as well
18 as for improvement of bone disease.

Item Type:	Article
Date Deposited:	02 May 2016 23:45
Last Modified:	02 May 2016 23:45
URI:	https://oak.novartis.com/id/eprint/23907