Introduction: HNSCC is a debilitating and deadly disease for which current treatments are extremely toxic and ineffective. Increasing data suggest that persistent cancer stem cells (CSC), resistant to standard chemo and radiation therapy, give rise to disease recurrence. Thus, poor outcomes may reflect ineffective CSC killing. CD44 is a promising therapeutic target that has two defined roles in tumorigenesis: it is a putative cancer initiating cell or CSC marker and it promotes migration and proliferation through interaction with EGFR, Rho and Ras signaling. Therefore therapies that target CD44 may destroy the CSC population, which is resistant to therapy while precisely eradicating the proliferating population of cancer cells. Methods: RO5429083 is a novel functional monoclonal antibody, developed by Roche, that targets a glycosylated, conformation dependent epitope of CD44. To evaluate CD44 as a therapeutic target in vivo, we established CAL 27 (HNSCC cell line) xenografts in nude mice and treated them with RO5429083 (Roche) in comparison to cisplatin (DPP), a conventional drug used in HNSCC treatment. After treatment, the mice were sacrificed, and the tumors were embedded in paraffin for IHC analysis. We also analyzed the effect of RO5429083 in vitro on peripheral blood lymphocytes (PBMCs). Results: RO5429083 treatment displayed a remarkable tumor growth inhibition in CAL 27 xenografts compared to DPP or control (P<0.005). Moreover, treatment with this new humanized antibody inhibited constitutive EGFR phosphorylation on CAL 27 xenografts. In addition, treatment of PBMCs from healthy donors with RO5429083 produced an expansion of cytolytic natural killer (NK) cells. Conclusion: Based on our studies the anti-CD44 antibody RO5429083 effectively inhibits tumor growth in the CAL 27 model of HNSCC. In addition to decreasing EGFR signaling, RO5429083 appears to have a protective effect on PBMCs and expands the NK cell population. In conclusion, we anticipate that anti-CD44 therapy will effectively target the stem cell population while boosting the number of NK cells, and thus may synergize with drugs that work via antibody-dependent cell-mediated cytotoxicity (ADCC) such as Cetuximab.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2521. doi:1538-7445.AM2012-2521