CD303 (BDCA-2) – a potential novel target for therapy in hematologic malignancies

Abstract

Plasmacytoid dendritic cells (pDCs) serve as immunoregulatory antigen-presenting cells that play a role in various inflammatory, viral, and malignant conditions. Malignant proliferation of pDCs is implicated in the pathogenesis of certain hematologic cancers, specifically blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myelogenous leukemia with clonal expansion of pDC (pDC-AML). In recent years, BPDCN and pDC-AML have been successfully treated with targeted therapy of pDC-specific surface marker, CD123. However, relapsed and refractory BPDCN remains an elusive cancer, with limited therapeutic options. CD303 is another specific surface marker of human pDCs, centrally involved in antigen presentation and immune tolerance. Monoclonal antibodies directed against CD303 have been studied in preclinical models and have achieved disease control in patients with cutaneous lupus erythematosus. We performed a comprehensive review of benign and malignant disorders in which CD303 have been studied, as there may be a potential future CD303-directed therapy for many of these conditions.

Keywords:

• CD303
• BDCA-2
• BPDCN
• pDC-AML
• targeted therapy
• monoclonal antibody

Disclosure statement

NP: Consulting/honorarium:AbbVie; Celgene; Stemline; Incyte; Novartis; MustangBio; Roche Diagnostics, LFB, Sanofi, ImmunoGen; Research funding/clinical trials support:Stemline; Novartis; AbbVie; Samus; Cellectis; Plexxikon; Daiichi-Sankyo; Affymetrix; Grants/funding:Affymetrix, SagerStrong Foundation.

LB: Co-owner of the patents: “Murine Anti-human OX40 monoclonal antibodies” and “Humanized Anti-human OX40 monoclonal antibodies for the treatment of cancer” licensed by M.D. Anderson Cancer Center (MDACC) to GlaxoSmithKline (GSK) for clinical development; “Anti-human HSP-70 monoclonal antibodies”, licensed to Asylia Therapeutics for clinical development. Co-owner of IDRs (Invention Disclosure Reports) for several monoclonal antibodies (including one clone of BDCA2) licensed to BD, eBioscience, Novus, Miltenyi, Abcam, etc. Co-owner of “Phage Display discoveries for the use in cancer treatment” sold by MDACC to Alvos Therapeutics.

SSN: Received personal fees from Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Bluebird Bio, and Unum Therapeutics; research support from Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics, Allogene Therapeutics, Precision Biosciences, and Acerta; royalties from Takeda Pharmaceuticals; and has intellectual property rights related to cell therapy.