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Poster display session

5465 - Synergistic Antitumor Effects of OT-101 (Trabedersen), a Transforming Growth Factor-beta 2 (TGF-β2) antisense oligonucleotide (ASO) and Chemotherapy in Preclinical Tumor Models

Date

11 Sep 2017

Session

Poster display session

Presenters

Osmond D'Cruz

Citation

Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390

Authors

O. D'Cruz, C. Lee, V. Trieu, L. Hwang

Author affiliations

  • Clinical Research, Autotelic Inc., 92626 - Costa Mesa/US
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Resources

Abstract 5465

Background

Overexpression of TGF-β2 has been implicated in the malignant progression of tumors by inducing immunosuppression, proliferation, angiogenesis and metastasis. OT-101 (Trabedersen) is a phosphorothioate ASO designed to specifically target human TGF-β2 mRNA. Herein, we report the synergizing effect of OT-101 with chemotherapy in multiple human tumor xenograft models for further exploration of clinical combination strategies.

Methods

OT-101 was administered as single agent (1-64 mg/kg, qdx3/wk or qdx21) and in combination with Gemcitabine (GEM, 15 mg/kg, qdx2/wk), Dacarbazine (DTIC, 1-10 mg/kg, qdx4/wk) or Paclitaxel (PTX, 10 mg/kg, qdx5) to nude mice (10/subgroup) bearing either (i) orthotopic human L3.6pl pancreatic cancer (PAC), (ii) human metastatic C8161 melanoma, (iii) SC glioblastoma (U87) or (iv) SC ovarian (SKOV-3) tumors. Mice were monitored for adverse effects, body weight loss, tumor size and survival outcome. Lymph node and liver surface and micro-metastases as well as size and weight of the pancreatic tumors were determined. Tumor sections were stained with anti-BrdUrd and CD31 antibodies to determine tumor cell proliferation and vascularization, respectively.

Results

OT-101 significantly reduced tumor growth (p = 0.0084), lymph node metastasis (p = 0.023), and tumor angiogenesis (p 

Conclusions

The preclinical data laid the groundwork for establishing combination therapies in the clinic. Of interest is the preferential synergy between OT-101 and PTX or DTIC, but not with GEM.

Clinical trial identification

Legal entity responsible for the study

Autotelic Inc

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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