Phase I study of sequential targeted gene delivery: Intravenous infusions of Rexin-G followed by Reximmune-C induce tumor necrosis and recruitment of tumor infiltrating lymphocytes in cancerous lesions
PubMed | Philippines; Epeius Biotechnologies Corporation
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016
3077 Background: Rexin-G and Reximmune-C are pathotropic nanoparticles bearing a cytocidal cyclin G1 gene and a granulocyte- macrophage colony stimulating factor (GM-CSF) gene respectively. The purpose of the Phase I study is to evaluate the safety and therapeutic potential of i.v. infusions of Rexin-G followed by Reximmune-C, in an effort to achieve a personalized cancer vaccination in vivo in patients with chemo-resistant solid tumors.Seven patients received Rexin-G i.v. at a dose of 4 x 10e10 cfu per day for 2 -6 weeks followed by Reximmune-C i.v. at 2.5 x 10e9 cfu or 5 x 10e10 cfu per day for 2 to 5 days (Cumulative Dose: 1.00 -1.25 x 10e10 cfu).There was no dose-limiting toxicity noted and GM-CSF protein was NOT detected in serum samples obtained during and after treatment with Reximmune-C. Immunologic reactions consisted of flu-like symptoms in two patients, redness and swelling of tumor-infiltrated cervical lymph node and metastatic chest nodule in two patients, swelling and acute left-sided flank pain in one patient with adrenal gland metastasis. In 2 cases, GM-CSF-expressing cancer cells were detected, by immunohistochemical staining, in tumors indicating successful targeted delivery in vivo of the GM-CSF gene. In one patient, the GM-CSF-positive cancer cells were surrounded by tumor-infiltrating lymphocytes (TILs), in addition to extensive tumor necrosis. Evaluation of the complement of recruited TILs by selective immunostaining showed significant numbers of both immunoreactive CD8+ killer T cells and CD68+ macrophages. Further, one patients biopsied tumor showed 100% tumor necrosis associated with TILs consisting of CD35+ dendritic cells, CD8+ killer T cells, and CD138+ plasma B cells suggesting a relatively mature immune response. The median progression-free survival was 2 months and the median over-all survival was 5 months.These studies demonstrate that (1) the functionality of the targeted gene delivery platform is profound, (2) the genetic constructs are relatively safe and (3) the potential for a personalized cancer vaccination in vivo using this sequential gene transfer approach is a realistic goal. [Table: see text].