OncoSec Medical Inc (ONCSQ)

[hschlauch]

http://clincancerres.aacrjournals.org/content/early/2018/06/05/1078-0432.CCR-18-1116.full-text.pdf

Age Correlates with Response to Anti-PD1, Reflecting Age-Related Differences in Intratumoral Effector and Regulatory T-Cell Populations

Curtis H. Kugel III, Stephen M. Douglass, Marie R. Webster, Amanpreet Kaur, Qin Liu, Xiangfan Yin, Sarah A. Weiss, Farbod Darvishian, Rami N. Al-Rohil, Abibatou Ndoye, Reeti Behera, Gretchen M. Alicea, Brett L. Ecker, Mitchell Fane, Michael J. Allegrezza, Nikolaos Svoronos, Vinit Kumar, Daniel Y. Wang, Rajasekharan Somasundaram, Siwen Hu-Lieskovan, Alpaslan Ozgun, Meenhard Herlyn, Jose R. Conejo-Garcia, Dmitry Gabrilovich, Erica L. Stone, Theodore S. Nowicki, Jeffrey Sosman, Rajat Rai, Matteo S. Carlino, Georgina V. Long, Richard Marais, Antoni Ribas, Zeynep Eroglu, Michael A. Davies, Bastian Schilling, Dirk Schadendorf, Wei Xu, Ravi K. Amaravadi, Alexander M. Menzies, Jennifer L. McQuade, Douglas B. Johnson, Iman Osman and Ashani T. Weeraratna

Results: Patients over the age of 60 responded more efficiently to anti-PD-1, and likelihood of response to anti-PD-1 increased with age, even when we controlled for prior MAPKi therapy. Placing genetically identical tumors in aged mice (52 weeks) significantly increased their response to anti-PD1 as compared with the same tumors in young mice (8 weeks). These data suggest that this increased response in aged patients occurs even in the absence of a more complex mutational landscape. Next, we found that young mice had a significantly higher population of regulatory T cells (Tregs), skewing the CD8+:Treg ratio. FOXP3 staining of human melanoma biopsies revealed similar increases in Tregs in young patients. Depletion of Tregs using anti-CD25 increased the response to anti-PD1 in young mice.

This article needs to be shared widely; overcoming intratumoral Tregs and Tregs in tumor draining lymph nodes should lead to vast improvements in responses, PFS, DOR, and OS for hard-to-treat metastatic cancers. I don't think there is any other company better positioned to make this possible than Oncosec. Tregs hijack antigen presentation intratumorally, peritumorally, and in lymphatic tissue. Once you solve that problem and allow priming to occur, then absolute Treg numbers won't matter so much. It is all about the Treg:CD8 ratio at the onset of the immune cycle. No company understands this better than Oncosec and its partners.