RRC ID 52531
著者 Kollmorgen G, Palme K, Seidl A, Scheiblich S, Birzele F, Wilson S, Clemens C, Voss E, Kaufmann M, Hirzel K, Rieder N, Krippendorff BF, Herting F, Niederfellner G.
タイトル A re-engineered immunotoxin shows promising preclinical activity in ovarian cancer.
ジャーナル Sci Rep
Abstract RG7787 is a re-engineered mesothelin-targeted immunotoxin with reduced immunogenicity composed of a humanized anti-mesothelin Fab fragment and a B-cell epitope silenced 24 kD fragment of Pseudomonas exotoxin A. High prevalence of mesothelin-positive cases and a large unmet medical need make ovarian cancer a promising indication for the clinical development of RG7787. However, ovarian cancer patients also frequently have elevated serum levels of the cancer antigen 125 (CA-125). In principle this could pose a problem, since the binding sites for CA-125 and RG7787 on mesothelin were reported to overlap. However, we show here that RG7787 can readily displace even excess amounts of CA-125 in different cellular assays. Moreover when tested in-vitro on a panel of 12 ovarian cancer cell lines, RG7787 had high cytotoxic activity on COV644, Caov-4, and SNU-119 cells and fully inhibited growth of EFO-21, KURAMOCHI, OVSAHO, and Caov-3 cells with potency values ranging from 1 to 86 pM. Finally, we evaluated the in-vivo efficacy of RG7787 in OvCa6668, a patient-derived ovarian cancer model with high levels of CA-125 expression. RG7787 had moderate monotherapy efficacy but in combination with standard chemotherapies (cisplatin, paclitaxel) achieved pronounced tumor regressions. In summary our data support clinical testing of RG7787 in ovarian cancer.
巻・号 7(1)
ページ 18086
公開日 2017-12-22
DOI 10.1038/s41598-017-17329-7
PII 10.1038/s41598-017-17329-7
PMID 29273809
PMC PMC5741731
MeSH Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use* Apoptosis / drug effects Cell Line, Tumor Cell Proliferation / drug effects* Female Humans Immunoconjugates / pharmacology Immunoconjugates / therapeutic use* Immunotoxins / pharmacology Immunotoxins / therapeutic use* Ovarian Neoplasms / drug therapy*
IF 3.998
引用数 2
リソース情報
ヒト・動物細胞 JHOS-2(RCB1521)