Pepinemab (VX15/2503) Nonclinical

Evans EE, Jonason AS Jr, Bussler H, Torno S, Veeraraghavan J, Reilly C, Doherty MA, Seils J, Winter LA, Mallow C, Kirk R, Howell A, Giralico S, Scrivens M, Klimatcheva K, Fisher TL, Bowers WJ, Paris M, Smith ES, Zauderer M. Antibody blockade of semaphorin 4D promotes immune infiltration into tumor and enhances response to other immunomodulatory therapies. Cancer Immunol Res. 2015 Jun;3(6): 689-701. http://www.ncbi.nlm.nih.gov/pubmed/25614511
Evans EE, Paris M, Smith ES, Zauderer M. Immunomodulation of the tumor microenvironment by neutralization of Semaphorin 4D. CInvited “Author’s View”. OncoImmunology, 2015. 4:12, e1054599, DOI: 10.1080/2162402X.2015.1054599 http://www.tandfonline.com/doi/full/10.1080/2162402x.2015.1054599
Leonard JE, Fisher TL2 Winter LA, Cornelius CA, Reilly C, Smith ES, Zauderer M. Nonclinical Safety Evaluation of VX15/2503; a Humanized IgG4 Anti-SEMA4D Antibody. Mol Cancer Ther. 2015 Feb 5 http://www.ncbi.nlm.nih.gov/pubmed/25657333
Fisher TL, Reilly CA, Winter LA, Pandina T, Jonason A, Scrivens M, Balch L, Bussler H, Torno S, Seils J, Mueller L, Huang H, Klimatcheva E, Howell A, Kirk R, Evans E, Paris M, Leonard JE, Smith ES, Zauderer M. Generation and preclinical characterization of an antibody specific for SEMA4D. Mabs. 2015 Oct 20. http://www.tandfonline.com/doi/abs/10.1080/19420862.2015.1102813
Smith ES, Jonason A, Reilly C, Veeraraghavan J, Fisher T, Doherty M, Klimatcheva E, Mallow C, Cornelius C, Leonard JE, Marchi N, Janigro D, Argaw AT, Pham T, Seils J, Bussler H, Torno S, Kirk R, Howell A, Evans EE, Paris M, Bowers WJ, John G, Zauderer M. SEMA4D compromises blood-brain barrier, activates microglia, and inhibits remyelination in neurodegenerative disease. Neurobiol Dis. 2014 Oct 18;73C:254-268. doi: 10.1016/j.nbd.2014.10.008. http://www.sciencedirect.com/science/article/pii/S0969996114003015
Southwell AL, Franciosi S, Villanueva EB, Xie Y, Winter LA, Veeraraghavan J, Jonason A, Felczak B, Zhang W, Kovalik V, Waltl S, Hall G, Pouladi MA, Smith ES, Bowers WJ, Zauderer M, Hayden MR. Anti-semaphorin 4D immunotherapy ameliorates neuropathology and some cognitive impairment in the YAC128 mouse model of Huntington disease. Neurobiol Dis. 2015 Feb 3; 76:46–56. http://www.sciencedirect.com/science/article/pii/S0969996115000145

 

Pepinemab (VX15/2503) Clinical

Amita Patnaik, Glen J. Weiss, John E. Leonard, Drew Warren Rasco, Jasgit C. Sachdev, Terrence L. Fisher, Christine Reilly, Laurie A. Winter, Robert B. Parker, Danielle Mutz, Lisa Blaydorn, Anthony W. Tolcher, Maurice Zauderer and Ramesh K. Ramanathan. Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of VX15/2503, a Humanized IgG4 anti-SEMA4D Antibody, in a First-In-Human Phase 1 Study of Patients with Advanced Solid Disease. Clin Cancer Res. 2015 Oct 7. http://clincancerres.aacrjournals.org/content/22/4/827.full.pdf+html
LaGanke, C., L. Samkoff, K. Edwards, L. Jung Henson, P. Repovic, S. Lynch, L. Stone, D. Mattson, A. Galluzzi, T. L. Fisher, C. Reilly, L. A. Winter, J. E. Leonard, and M. Zauderer. 2017. Safety/tolerability of the anti-semaphorin 4D Antibody VX15/2503 in a randomized phase 1 trial. Neurol Neuroimmunol Neuroinflamm 4: e367. https://www.ncbi.nlm.nih.gov/pubmed/28642891
Fisher, T. L., J. Seils, C. Reilly, V. Litwin, L. Green, J. Salkowitz-Bokal, R. Walsh, S. Harville, J. E. Leonard, E. Smith, and M. Zauderer. 2016. Saturation monitoring of VX15/2503, a novel semaphorin 4D-specific antibody, in clinical trials. Cytometry B Clin. Cytom. 90: 199-208. http://onlinelibrary.wiley.com/doi/10.1002/cyto.b.21338/abstract

 

Platform

Antibody library display on a mammalian virus vector: combining the advantages of both phage and yeast display into one technology
Curr Drug Discov Technol. 2014 Mar;11(1):48-55 – March 2014
Smith ES, Zauderer M. <PDF>
Antibody Selection from Immunoglobulin Libraries Expressed in Mammalian Cells.
In Therapeutic Antibodies: From Bench to Clinic. Edited by Zhiqiang An. 2009 p283-307. – January 2009
Smith ES, Zauderer M.
In vitro generation of tumor specific T cells that recognize a shared antigen of AML: molecular characterization of TCR genes.
Leuk Res. 2007 Feb;31(2):195-202 – February 2007
Coppage M, Belanger T, Zauderer M, Sahasrabudhe D.
Construction of cDNA Libraries in Vaccinia Virus
Methods in Molecular Biology 269: 65-75 – January 2004
Smith, E.S., S. Shi, and M. Zauderer
Lethality-Based Selection of Recombinant Genes in Mammalian Cells: Application to Identifying Tumor Antigens
Nature Medicine 7: 967-972. 2001 – August 2001
Smith, E S.., A. Mandokhot, E. Evans, L. Mueller, M.A. Borrello, D. Sahasrabudhe, and M. Zauderer.
Construction and characterization of vaccinia direct ligation vectors.
Virology. 1997 Nov 24;238(2):444-51. – November 1997
Merchlinsky M, Eckert D, Smith E, Zauderer M. <PDF>

 

VX35

C35: A new Prognostic Tool and Potential Target in Prostate Cancer
ASCO 2013 Genitourinary Cancers Symposium – January 2013
Deepak Kilari, Jorge Yao, Emil Scosyrev, Elizabeth Evans, and Deepak Sahasrabudhe
A gene on the HER2 amplicon, C35, is an oncogene in breast cancer whose actions are prevented by inhibition of Syk.
British Journal of Cancer (2010), 1 –10 – July 2010
E Katz, S Dubois-Marshall, AH Sims, D Faratian, J Li, ES Smith, JA Quinn, M Edward, RR Meehan, EE Evans, SP Langdon and DJ Harrison <PDF>
C35 (C17orf37) Is A Novel Tumor Biomarker Abundantly Expressed in Breast Cancer
Mol Cancer Ther. 5(11):2919–30 – November 2006
Evans, E.E., Henn, A.D., Jonason, A., Paris, M.J., Schiffhauer, L.M., Borrello, MA, Smith, ES, Sahasrabudhe DM, Zauderer M <PDF>

 

NKT

CD1d-antibody fusion proteins target iNKT cells to the tumor and trigger long-term therapeutic responses.
Cancer Immunol Immunother. 2013 Apr;62(4):747-60 – April 2013
Corgnac S, Perret R, Derré L, Zhang L, Stirnemann K, Zauderer M, Speiser DE, Mach JP, Romero P, Donda A. <PDF>
Sustained activation and tumor targeting of NKT cells using a CD1d-anti-HER2-scFv fusion protein induce antitumor effects in mice.
J Clin Invest. 2008 Mar;118(3):994-1005 – March 2008
Stirnemann K, Romero JF, Baldi L, Robert B, Cesson V, Besra GS, Zauderer M, Wurm F, Corradin G, Mach JP, Macdonald HR, Donda A. <PDF>