Data from Targeting Podoplanin for the Treatment of Osteosarcoma

• DOI: 10.1158/1078-0432.c.6532485.v1
• Publication Date: 2023-04-01T03:00:05Z
• Authors: Ai Takemoto; Satoshi Takagi; Takao Ukaji; Nobuhiko Gyobu; Mamoru Kakino; Miho Takami; Asami Kobayashi; Marie Lebel; Tokuichi Kawaguchi; Minoru Sugawara; Kazue Tsuji-Takayama; Kenji Ichihara; Yuki Funauchi; Keisuke Ae; Seiichi Matsumoto; Yoshiya Sugiura; Kengo Takeuchi; Tetsuo Noda; Ryohei Katayama; Naoya Fujita
• Keywords: Podoplanin

<div>AbstractPurpose:<p>Osteosarcoma, the most common bone malignancy in children, has a poor prognosis, especially when tumor metastasizes to lungs. Therefore, novel therapeutic strategies targeting both proliferation and metastasis of osteosarcoma are required. Podoplanin (PDPN) is expressed by various tumors associated with tumor-induced platelet activation via its interaction C-type lectin-like receptor 2 (CLEC-2) on platelets. We previously found that PDPN contributed growth through activation; thus, this study, we developed an anti-PDPN humanized antibody evaluated effect metastasis.</p>Experimental Design:<p>Nine cell lines two patient-derived cells were collected, efficacy anti-DPN-neutralizing PG4D2 AP201, which had IgG4 framework region. The antitumor antimetastasis AP201 examined <i>in vitro</i> vivo</i>. In addition, signaling between CLEC-2 was analyzed using phospho-RTK (receptor tyrosine kinase) array, assay, or immunoblot analysis under supression RTKs knockout inhibitor treatment.</p>Results:<p>We observed treatment significantly suppressed pulmonary xenograft models highly expressing PDPN. contribution PDGFR activated releasates confirmed, antibody, vivo</i> without significant adverse events.</p>Conclusions:<p>Targeting neutralizing against PDPN–CLEC-2 antibody-dependent cell-mediated cytotoxicity complement-dependent strategy for PDPN-positive osteosarcoma.</p></div>