A seemingly forgotten, off-the-shelf cancer gene therapy from the early 2000s appears to be getting a revival. Eight cancer patients who received the therapy a decade ago are still alive, and the features of these super responders were reported at the 2019 American Society of Gene and Cell Therapy (ASGCT) annual meeting in Washington, D.C.1,2 And now, phase 2 trials are being planned to further evaluate the therapy.
The tumor-targeted gene therapy, known as DeltaRex-G (formerly Rexin-G), works by delivering a retroviral vector to tumor cells that encodes for an anticyclin G1 construct that is meant to inhibit the cyclin G1 gene (CCNG1), leading to cell death. The first-in-human study was conducted in the Philippines in 2002 with patients who had chemotherapy-resistant solid tumors.
Epeius Biotechnologies Corporation, a company founded in 2004 by Frederick l. Hall, PhD, and Elinda M. Gordon, MD, (who are also the coinventors of the therapy), sponsored the launch of several clinical trials in the United States to continue to evaluate DeltaRex-G across various chemotherapy-resistant metastatic cancer indications: breast cancer (ClinicalTrials.gov Identifier: NCT00505271), pancreatic cancer (ClinicalTrials.gov Identifier: NCT00504998), osteosarcoma (ClinicalTrials.gov Identifier: NCT00572130), and sarcoma (ClinicalTrials.gov Identifier: NCT00505713).
DeltaRex-G was also evaluated in combination with DeltaVax (formerly Reximmune-C) in another clinical trial in the Philippines. DeltaVax delivers a granulocyte-macrophage colony-stimulating factor (GM-CSF) expression construct, and the rationale behind the combination is that DeltaRex-G kills the tumors while DeltaVax recruits immune cells to the tumor.
As a result of the safety and efficacy seen in trials, DeltaRex-G gained orphan drug designation from the US Food and Drug Administration (FDA) in the United States for osteosarcoma and soft tissue sarcoma in 2008 and fast-track designation for pancreatic cancer in 2009.3 In 2007, DeltaVax gained accelerated approval for all solid tumors in the Philippines.3