SAN MARINO, Calif., May 27 Epeius Biotechnologies(http://www.epeiusbiotech.com) announced today that the results of a Phase IFeasibility Study of sequential targeted gene delivery -- using Rexin-Gfollowed by Reximmune-C -- for cancer vaccination will be presented at theASCO meetings in Chicago on June 1, 2008 (J Clin Oncol 26:3077, 2008). Rexin-Gand Reximmune-C are pathotropic (disease-seeking) nanoparticles bearing acytocidal cyclin G1 gene and a granulocyte-macrophage colony stimulatingfactor (GM-CSF) gene, respectively. When injected intravenously, thesetargeted vectors seek out and accumulate in cancerous lesions, thus increasingthe effective local concentrations of the therapeutic nanoparticles within thetumors.
The working hypothesis behind this two-stage approach to cancer managementpredicts that strategic and individualized vaccination of a patient againsthis/her own cancer can be achieved by combining (1) the targeted vectorbearing a potent cytocidal construct, Rexin-G, with (2) a targeted vectorbearing an immune activating gene, Reximmune-C. Rexin-G is given first tokill the cancer cells and thus expose neoantigens within the tumors, followedby Reximmune-C to recruit the body's immune cells into the same tumorcompartments, thereby prompting recognition of the tumor neoantigens in situand inducing long-lasting anti-tumor immunity.
The purpose of the Phase I study was to evaluate the overallsafety/toxicity and therapeutic potential of this sequential regimen, in aneffort to achieve a personalized cancer vaccination in vivo. Seven patientswith chemo-resistant cancer, including carcinoma of breast, colon andpancreas, non-small cell lung cancer and leiomyosarcoma, received Rexin-G i.v.at a dose of 4 x 10e10 cfu per day for 2 to 6 weeks (Cumulative Dose: 4.0 x10e11 to 1.2 x 10e12 cfu) followed by Reximmune-C i.v. at 2.5 x 10e9 cfu for 5days or 5 x 10e9 cfu for 2 days (Cumulative Dose: 1.00 -1.25 x 10e10 cfu).
Analysis of Safety showed that no dose-limiting toxicity was observed withthis regimen, and immunoreactive GM-CSF protein was NOT detected in serumsamples either during or after treatment with Reximmune-C. There was nosignificant alteration in hemodynamic function, bone marrow suppression,liver, kidney, or any other organ dysfunction related to the intervention.Immune-related reactions consisted of transient flu-like symptoms in twopatients, redness and swelling of a tumor-infiltrated lymph node and onemetastatic chest nodule, and acute flank pain in one patient with adrenalgland metastasis. Analysis of efficacy in biopsied tumor specimens revealeddefinitive expression of the GM-CSF transgene in cancer cells indicatingeffective gene delivery in vivo. Further, extensive tumor necrosis and tumorinfiltrating lymphocytes (TILs) were observed within the tumors.Characterization of the recruited TILs showed CD35+ dendritic cells, CD8+killer T cells, and CD138+ plasma B cells, with lesser amounts of CD68+macrophages and CD20+ B cells, suggesting a relatively mature or advancedimmune response. Taken together, this landmark study demonstrates (1) that thefunctionality of the gene delivery platform is profound; (2) the geneticconstructs employed are relatively safe; and (3) the potential for apersonalized cancer vaccination using this sequential gene transfer approachis now a realistic goal.
For more information about Rexin-G, Reximmune-C, on-going clinical trialsin the USA and abroad, and/or Epeius pathotropic (disease-seeking) genedelivery systems, please contact Dr. Erlinda M. Gordon [email protected]
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SOURCE Epeius Biotechnologies