Targeting DKK1 with a DNA Vaccine to Prevent Development of Multiple Myeloma

University Of Tx Md Anderson Can Ctr, Houston TX

Investigators

Abstract

Multiple myeloma (MM) remains an incurable plasma cell cancer despite great advancements in chemo- and immunotherapies. All MM patients have preceding asymptomatic stages which primarily consist of monoclonal gammopathy of undetermined significance (MGUS), which is often followed by development of a more severe condition called smoldering MM (SMM). Patients with MGUS, and especially SMM, convert to overt MM and no therapeutic methods are available to prevent their progression to MM. Therefore, this is an unmet need to develop chemo- and/or immunoprevention strategies for MGUS and SMM. Dickkopf-1 (DKK1) may be an excellent target for this purpose. DKK1 is absent from normal tissues including normal bone marrow (BM) plasma cells but is highly expressed in BM plasma cells from MGUS and SMM patients, and their expression is further elevated in MM cells. Our studies showed that DKK1 was an excellent tumor-associated antigen (TAA), and DKK1 vaccine was therapeutic against established MM in vivo. The objective of this project is to, for the first time, determine the potential of targeting DKK1 by a vaccine for immunoprevention of MM development. This work will support the clinical development of novel immune-based, less toxic (than chemotherapy) treatments for patients with MGUS or SMM to prevent progression to overt MM. Completing these studies are highly significantly and clinically impactful, as DKK1-specific humanized mAbs are already available and have been tested in human cancers.