Targeting Glioblastoma

Glioblastoma, or glioblastoma multiforme (GBM), is a rare disease, with a global incidence of <10 per 100,000 people; the prognosis is very poor.  Here are a couple of recent studies testing targeted saporin therapies.

Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival.
Munksgaard Thorén M, Chmielarska Masoumi K, Krona C, Huang X, Kundu S, Schmidt L, Forsberg-Nilsson K, Floyd Keep M, Englund E, Nelander S, Holmqvist B, & Lundgren-Åkerlund E.
Cancers, 11 (4):587, 2019
Objective:  To investigate the potential of integrin α10β1 as a therapeutic target in  glioblastomas (GBMs).
Summary:  integrin α10β1 has a crucial role in the migration, proliferation, and survival of GBM cells and that an integrin α10β1 antibody–drug conjugate induced cell death of GBM cells both in vitro and in vivo.
Dose:  Infusions of anti-10-SAP or Anti-ctrl-SAP were made icv (1 µg/2 L per infusion).

Expression of Different Neurokinin-1 Receptor (NK1R) Isoforms in Glioblastoma Multiforme: Potential Implications for Targeted Therapy.
Cordier D, Sailer M, Gerber A, Kluba C, Bauman A, Hutter G, Mindt TL, Mariani L.
Cancer Biother Radiopharm Epub2014.
The neurokinin-1 receptor (NK1r) has been found to be consistently over-expressed in gliomas, making it a potential target for therapeutic strategies. However, treatments with therapies utilizing substance P (SP), the ligand for the NK1r, have at best yielded uneven results. In this work the authors investigated factors that may predict the response to therapies directed at NK1r gliomas. SSP-SAP (Cat. #IT-11) was used at a concentration of 1 nM in cytotoxicity assays on several different glioma cell lines. Using this and other data it was shown that only the cell line with the most full-length NK1r RNA transcripts displayed high levels of binding, internalization, and cell killing necessary for NK1r to be a therapeutic target using SP.

Targeting of the receptor protein tyrosine phosphatase beta with a monoclonal antibody delays tumor growth in a glioblastoma model.
Foehr ED, Lorente G, Kuo J, Ram R, Nikolich K, Urfer R.
Cancer Res 66(4):2271-2278, 2006.
The receptor protein tyrosine phosphatase ß (RPTPß) is overexpressed in astrocytomas, and is a potential target for tumor therapy. After testing antibodies against an extracellular domain of RPTPß in vitro with Mab-ZAP (Cat. #IT-04), two custom conjugates, 7E4B11-SAP and 7A9B5-SAP, were created by Advanced Targeting Systems. The authors tested the custom conjugates, using anti-DAT-SAP (Cat. #IT-25) as a positive control, and mouse IgG-SAP (Cat. #IT-18) as a negative control. The 7E4B11-SAP conjugate displayed significant antitumor activity in mice engrafted with U87 glioma cells.

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