Long Term Follow Up: Phase I Trial of Â“bi-shRNA furin/GMCSF DNA/Autologous Tumor CellÂ” Immunotherapy (FANGÂ™) in Advanced Cancer
Neil Senzer1-4, Minal Barve3, Jacklyn Nemunaitis1, Joseph Kuhn5, Anton Melnyk6, Peter Beitsch4, Mitchell Magee7, Jonathan Oh3, Cynthia Bedell1, Padmasini Kumar2, Donald D Rao2, Beena O Pappen2, Gladice Wallraven2, Charles Brunicardi F8, Phillip B Maples2 and John Nemunaitis1-4*
- *Corresponding Author:
- John Nemunaitis
1700 Pacific, Suite 1100
Dallas, Texas 75201, USA
E-mail: [email protected]
Received date: September 27, 2013; Accepted date: October 26, 2013; Published date: October 30, 2013
Citation: Senzer N, Barve M, Nemunaitis J, Kuhn J, Melnyk A, et al. (2013) Long Term Follow Up: Phase I Trial of “Bi-Shrnafurin/GMCSF DNA/Autologous Tumor Cell” Immunotherapy (FANG™) in Advanced Cancer. J Vaccines Vaccin 4:209. doi: 10.4172/2157-7560.1000209
Copyright: © 2013 Senzer N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Study Background: Previously, we demonstrated safety and correlated induced immune response with survival in a Phase I study of FANG immunotherapy in advanced cancer patients. We now report long term follow-up (FU) of Phase I treated patients including assessment of relationships of dose, γIFN-ELISPOT response, and patient demographics to safety and survival. Methods: Safety, γIFN-ELISPOT response, and survival have been followed through 3+ years in advanced cancer patients who received ≥ 2-12 intradermal monthly injections of 1×107 or 2.5×107 cells/injection. Clinical and serological assessments were performed monthly, radiographic evaluations bimonthly, and γ-IFN-ELISPOT at baseline, and start of Cycle 2, 4, 6, 9, 12 then sequentially at FU. Results: Previously, we reported results on 45 patients with successful FANG construction followed for 1 year (28 treated (designated FANG); 17 not treated based on availability of other alternative treatments or failed manufacturing (designated No FANG)). We now report FU results through year 3 on those patients and an additional 29 patients (7 FANG, 22 No FANG) subsequently entered into Phase I study (total N=35 FANG; total N=39 No FANG). The median survival of the current expanded Phase I trial population is 562 days vs. 122 days (p=0.00001). This is similar to the originally published data from two years earlier. The γ-IFN-ELISPOT reaction was positive in 14 of the current FANG treated patients and negative in 12 FANG treated patients at Month 3 or less post first injection. Survival correlated with γ-IFN-ELISPOT reaction; median 836 days vs. 440 days with positive and negative ELISPOT respectively, (p=0.04). No long term adverse toxicity has been seen and there was no significant correlation of immune response or survival with either dose or demographics. Conclusions: Treatment with FANG vaccine continues to show long term safety and evidence of benefit in patients with many types of advanced cancer thereby justifying further efficacy testing.