Investigation of factors affecting the efficacy of 3C23K, a human monoclonal antibody targeting MISIIR

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

MISIIR is a potential target for ovarian cancer (OC) therapy due to its tissue-specific pattern of expression. 3C23K is a novel therapeutic monoclonal anti-MISIIR antibody designed to recruit effector cells and promote cell death through ADCC (antibody dependent cell-mediated cytotoxicity). Our objective was to determine the tolerability and efficacy of 3C23K in OC patient-derived xenografts (PDX) and to identify factors affecting efficacy. Quantitative RT-PCR, immunohistochemistry (IHC), and flow cytometry were used to categorize MISIIR expression in established PDX models derived from primary OC patients. We selected two high expressing models and two low expressing models for in vivo testing. One xenograft model using an MISIIR over-expressing SKOV3ip cell line (Z3) was a positive control. The primary endpoint was change in tumor size. The secondary endpoint was final tumor mass. We observed no statistically significant differences between control and treated animals. The lack of response could be secondary to a number of variables including the lack of known biomarkers of response, the low membrane expression of MISIIR, and a limited ability of 3C23K to induce ADCC in PDX models. Further study is needed to determine the magnitude of ovarian cancer response to 3C23K and also if there is a threshold surface expression to predict response.

Original languageEnglish (US)
Pages (from-to)85214-85223
Number of pages10
JournalOncotarget
Volume8
Issue number49
DOIs
StatePublished - Oct 17 2017

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Heterografts
Ovarian Neoplasms
Monoclonal Antibodies
Antibody-Dependent Cell Cytotoxicity
Anti-Idiotypic Antibodies
Neoplasms
Flow Cytometry
Cell Death
Biomarkers
Immunohistochemistry
Cell Line
Polymerase Chain Reaction
Membranes
Therapeutics

Keywords

  • 3C23K
  • Mullerian inhibiting substance receptor
  • Ovarian cancer
  • Patient-derived xenograft
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology

Cite this

Investigation of factors affecting the efficacy of 3C23K, a human monoclonal antibody targeting MISIIR. / Gill, Sarah E.; Zhang, Qing; Keeney, Gary; Cliby, William Arthur; Weroha, Saravut (John).

In: Oncotarget, Vol. 8, No. 49, 17.10.2017, p. 85214-85223.

Research output: Contribution to journalArticle

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