FANG™ Vaccine
The autologous tumor cell FANG™ vaccine expresses rhGMCSF and the bifunctional RNAi effector, bi-shRNAfurin…
FANG™ Vaccine
The autologous tumor cell FANG™ vaccine expresses rhGMCSF and the bifunctional RNAi effector, bi-shRNAfurin. The GMCSF protein is a potent stimulator of the immune system, recruiting and activating antigen presenting cells at the site of intradermal injection thereby promoting antigen presentation. The furin bifunctional shRNA blocks furin protein production via mRNA degradation and translational inhibition. Furin is a proprotein convertase primarily responsible for activation of the TGFβ1 and 2 isoforms and its inhibition decreases the activational conversion of the latent TGFβ proprotein to the mature immunosuppressive TGFβ1 and TGFβ2 isoforms. Insofar as the TGFβ1 and TGFβ2 isoforms can induce further TGFβ production via a positive feedback loop, inhibition of the former effectively reduces production of the latter. Both the ubiquitous expression of the TGFβ1 and 2 isoforms as well as the inhibitory effects of these isoforms on GMCSF immune modulatory function support a broad based tumor target range for the testing of a pan-TGFβ suppressed/GMCSF expressing, afferent immune enhancing, vaccine.
Related Clinical Trials
Phase I
Advanced Solid Tumors
HYPERLINK:
http://clinicaltrials.gov/ct2/show/NCT01061840
http://mccrc.clinisite.com/index.php?q=node/596
Phase II
High Risk Stage IIIc Ovarian Cancer
HYPERLINK:
http://clinicaltrials.gov/ct2/show/ NCT01309230
http://mccrc.clinisite.com/index.php?q=node/693
Recruiting
FANG™ Vaccine
Phase II
Advanced Melanoma
Phase II Trial of FANG™ Autologous Tumor Cell Vaccine in Advanced Melanoma (CL-PTL-114)
HYPERLINK:
http://clinicaltrials.gov/ct2/show/ NCT01453361
http://mccrc.clinisite.com/index.php?q=node/713
Recruiting
FANG™ Vaccine
Phase II
Colorectal Cancer
Randomized Phase II Trial of Post-operative Adjuvant Chemotherapy ± FANG™ Autologous Tumor Cell Vaccine in Colorectal Carcinoma with Liver Metastases (CL-PTL-107)
Recruiting
References
Senzer N, Barve M, Kuhn J, Melnyk A, Beitsch P, Lazar M, Lifshitz S, Magee M, Oh J, Mill SW, Bedell C, Higgs C, Kumar P, Yu Y, Norvell F, Phalon C, Taquet N, Rao DD, Wang Z, Jay CM, Pappen BO, Wallraven G, Brunicardi FC, Shanahan DM, Maples PB, Nemunaitis J: Phase I Trial of “bi-shRNAifurin/GMCSF DNA/Autologous Tumor Cell” Vaccine (FANG™) in Advanced Cancer. Molecular Therapy 2012; 20(3):679-686.
HYPERLINK:
http://www.nature.com/mt/journal/v20/n3/pdf/mt2011269a.pdf
Maples PB, Kumar P, Yu Y, Wang Z, Jay CM, Pappen BO, Rao DD, Kuhn J, Nemunaitis J, Senzer N: FANG Vaccine: Autologous Tumor Cell Vaccine Genetically Modified to Express GM-CSF and Block Production of Furin. BioProcessing Journal 2010; 8(4):4-14.