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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
OM-RCA-01, a novel humanized monoclonal antibody targeting fibroblast growth factor receptor 1, in renal cell
Ilya Tsimafeyeu1, Elina Zaveleva, Evgenia Stepanova
1Kidney Cancer Research Bureau, Bazovskaya ul. 4/1-15, Moscow, 125635, Russian Federation, tsimafeyeu@gmail.com.
Abstract:
Fibroblast growth factor (FGF) receptor 1 (FGFR1) is a potential therapeutic target for treatment of metastatic renal cell carcinoma (RCC). We investigated the preclinical activity of OM-RCA-01, a novel therapeutic humanized anti-FGFR1 antibody in RCC. OM-RCA-01 has been shown to inhibit in vitro kinase activity of FGFR1 and has high affinity (Kd of 1.59 nM). In human renal carcinoma Caki-1 FGFR1-expressing cells, OM-RCA-01 potently inhibited FGF-mediated signaling and proliferation. In vivo, the tumors in untreated mice or mice treated with non-specific IgG continued their aggressive growth to reach the size of 2,000 cm3, at which point the mice were killed. In contrast, treatment with OM-RCA-01 not only significant arrested further growth of the tumors (P < 0.01) but also demonstrated differences in tumor volume compared with vehicle already on Day 13. A similar anti-tumor activity of OM-RCA-01 was observed when the antibody was given in low (1 mg/kg) or high (10 mg/kg) doses (P = 0.917). In Matrigel assay, OM-RCA-01 significantly inhibited FGF-induced endothelial cell migration, capillary-like tubular structure and mature vessels formation. Administration of 10 mg/kg antibody for up to 35 days resulted in minimal body weight loss and no observations of gross toxicity were made. Collectively, the data obtained with OM-RCA-01 are consistent with potent inhibition of FGFR1-signaling, angiogenesis, and tumor growth. OM-RCA-01 is being developed clinically as an intravenous therapy for the treatment of clear cell RCC.
Insights
A novel antibody, OM-RCA-01, effectively targets Fibroblast Growth Factor Receptor 1 (FGFR1) in preclinical models of renal cell carcinoma (RCC). This therapy significantly inhibits tumor growth and angiogenesis, showing promise for clear cell RCC treatment.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Metastatic renal cell carcinoma (RCC) remains a significant clinical challenge.
- Fibroblast Growth Factor Receptor 1 (FGFR1) is implicated in RCC pathogenesis and represents a potential therapeutic target.
- Novel targeted therapies are needed to improve outcomes for RCC patients.
Purpose of the Study:
- To investigate the preclinical efficacy of OM-RCA-01, a humanized anti-FGFR1 antibody, in models of renal cell carcinoma.
- To evaluate the anti-tumor activity and anti-angiogenic effects of OM-RCA-01.
- To assess the safety profile of OM-RCA-01 in vivo.
Main Methods:
- In vitro kinase inhibition assays and cell proliferation studies using Caki-1 cells.
- In vivo efficacy studies in mice bearing established RCC tumors.
- Matrigel assay to assess anti-angiogenic potential.
- Toxicology assessment including body weight monitoring and gross observation.
Main Results:
- OM-RCA-01 demonstrated high affinity for FGFR1 and potently inhibited FGF-mediated signaling and proliferation in FGFR1-expressing RCC cells.
- In vivo, OM-RCA-01 significantly arrested tumor growth in a dose-dependent manner and showed efficacy at both low and high doses.
- OM-RCA-01 significantly inhibited FGF-induced endothelial cell migration and angiogenesis.
- The antibody was well-tolerated in vivo with minimal toxicity.
Conclusions:
- OM-RCA-01 exhibits potent anti-tumor activity against RCC by inhibiting FGFR1 signaling and angiogenesis.
- Preclinical data support the development of OM-RCA-01 as a potential intravenous therapy for clear cell RCC.
- OM-RCA-01 represents a promising targeted therapeutic candidate for metastatic renal cell carcinoma.
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