male4Ben Wen, PhD
(Co-Mentor: Glenn Dranoff, MD)

Genomics Institute of the Novartis Research Foundation
San Diego, California, United States

T cell exhaustion has become a central theme in understanding how tumors evade immune responses, helped in large part by clinical validation of T cell checkpoint blockade in various cancer settings.  It is clear, however, that the current treatments available are limited in scope, but the potential for durable responses is evident.  By gaining further understanding of the T cell effector and exhaustion programs, we aim to develop improved therapeutics that enhance clinical response rates.  Therefore, a current focus of our research is to utilize the chronic infection model of LCMV to perform unbiased screens to identify novel modulators of T cell exhaustion.  These studies will utilize proprietary genomics tools and libraries that encompass the entire transcriptome and will enable the identification of novel modifiers of T cell exhaustion that could then be further validated via genetic and pharmacological methods.  In addition, elucidation of responses can be performed at the molecular and cellular level to fully understand how the T cell exhaustion program is initiated and reversed.  These methodologies include, but are not limited to, gene expression, TCR repertoire, and CyTOF (mass cytometry) analyses.  With these tools, our goal is to identify the next generation of T cell-mediated cancer immunotherapies.

Selected Publications

Selected Publications for Ben Wen 

Inhibition of the inositol kinase Itpkb augments calcium signaling in lymphocytes and reveals a novel strategy to treat autoimmune disease.
Miller AT, Dahlberg C, Sandberg ML, Wen BG, Beisner DR, Hoerter JA, Parker A, Schmedt C, Stinson, M, Avis J, Cienfuegos C, McPate M, Tranter P, Gosling M, Groot-Kormelink PJ, Dawson J, Pan S, Tian SS, Seidel HM, Cooke MP.
PLoS One. 2015 Jun:10(6):e0131071.

A deficiency in Drak2 results in a T cell hypersensitivity and an unexpected resistance to autoimmunity.
McGargill MA, Wen BG, Walsh CM, Hedrick SM.
Immunity. 2004 Dec:21(6):781-91.

Inositol (1,4,5) trisphosphate 3 kinase B controls positive selection of T cells and modulates Erk activity.
Wen BG, Pletcher MT, Warashina M, Choe SH, Ziaee N, Wiltshire T, Sauer K, Cooke MP.
Proc Natl Acad Sci USA. 2004 Apr:101(15):5604-9.

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Selected Publications for Glenn Dranoff

Cancer Immunology Research: A Two-Year Anniversary.
Dranoff G.
Cancer Immunol Res. 2015 Jul:3(7):703.

Biologic activity of autologous, granulocyte-macrophage colony-stimulating factor secreting alveolar soft-part sarcoma and clear cell sarcoma vaccines.
Goldberg JM, Fisher DE, Demetri GD, Neuberg D, Allsop SA, Fonseca C, Nakazaki Y, Nemer D, Raut CP, George S, Morgan JA, Wagner AJ, Freeman GJ, Ritz J, Lezcano C, Mihm M, Canning C, Hodi FS, Dranoff G.
Clin Cancer Res. 2015 Jul:21(14):3178-86.

Immunotherapy at large: Balancing tumor immunity and inflammatory pathology.
Dranoff G.
Nat Med. 2013 Sep:19(9):1100-1.

Click here for additional publications.