? Rexin-G is the first in a series of targeted injectable vectors being developed by Epeius Biotechnologies Corporation for the treatment of metastatic cancer. Molecularly engineered to exhibit a """"""""pathotropic"""""""" (i.e. disease-seeking) targeting function, Rexin-G has been shown to preferentially deliver a cytocidal gene to metastatic and remote cancerous lesions in preclinical and clinical studies. In the first six patients with end-stage pancreatic cancer, repeated infusions of Rexin-G induced tumor regression or tumor growth stabilization (Gordon et at, 2004) without the deleterious side effects usually associated with chemotherapy. Based on demonstrations of medical plausibility as an effective treatment for pancreatic cancer, the most lethal of all cancers (prevalence about 30,000), Rexin-G gained orphan drug designation in 2003. The working hypothesis is that the pathotropic targeting of Rexin-G retroviral vector by specifically increasing the effective local concentration in cancerous lesions enhances both the safety and efficacy of its gene-transfer function. The investigators propose this Phase 1 clinical trial that will provide basic research in clinical pharmacology and toxicology to test the safety of Rexin-G for patients with pancreatic cancer. The results will help lead to the commercialization of Rexin-G as the much sought after targeted gene courier, that delivers cytocidal genes to previously inaccessible cancerous lesions. ? ? The project has 5 specific aims: ? ? Aim 1: To evaluate the toxicological effects of escalating doses of Rexin-G on hematologic and nonhematologic parameters, using standard blood cell counting and serum chemistry panels ? ? Aim 2: To evaluate the pharmacokinetics of intravenous (IV) infusions of Rexin-G administered in escalating doses by measuring vector titers in serum samples using standard Neo assays ? ? Aim 3: To quantify the incidence of vector integration in non-target organs (i.e. peripheral blood lymphocytes and semen) of patients receiving escalating IV doses of Rexin-G using PCR assays ? ? Aim 4: To evaluate the potential of repeated infusions of Rexin-G to evoke immune responses by testing for the presence of anti-vector antibodies using vector neutralization assays and Western blot analysis ? ? Aim 5: To determine the potential occurrence of recombination events that could favor the generation of CRiJ peripheral blood lymphocytes using PCR assays. ? ? While the Phase 1 clinical trial includes evaluation of potential tumor response, the focus of this study is on the establishment of safety, which will, if determined, lead to future Phase 2 and Phase 3 clinical trials. These initial studies comprise the early logical steps taken towards advancing Rexin-G to commercialization for the effectual treatment of pancreatic cancer. ? ?
| Chawla, Sant P; Chua, Victoria S; Fernandez, Lita et al. (2010) Advanced phase I/II studies of targeted gene delivery in vivo: intravenous Rexin-G for gemcitabine-resistant metastatic pancreatic cancer. Mol Ther 18:435-41 |
