OncoSec Medical Inc (ONCSQ)

[guti]

More proof you ask for, but I can only give you proof of what the science has.
The following is from the article “Macrophage IL-10 Blocks CD8+ T Cell-Dependent Responses to Chemotherapy by Suppressing IL-12 Expression in Intratumoral Dendritic Cells”

“Therapeutics targeting the CSF-1/CSF-1 receptor pathway are currently being evaluated clinically in multiple cancer types, either as monotherapy or in combination with standard-of-care chemotherapy. However, mechanisms by which the CSF-1/CSF-1 receptor pathway and macrophages sustain tumor growth and/or repress response to cytotoxic therapy are unclear. Herein we report that macrophages infiltrating mammary carcinomas are the significant source of IL-10, which in turn suppresses intratumoral dendritic cell production of IL-12 and thereby limits cytotoxic T cell responses during chemotherapy. These data reveal a role for the interaction between tumor macrophages and dendritic cells in mediating response to therapy, identify a CSF-1/IL-10/IL-12 cytokine axis for targetable intervention, and reveal possible risk stratification biomarkers for patient selection.” Page#1.

“Blocking IL-10R has not been used extensively as an approach for anticancer therapy but has been reported to induce tumor regression in combination with CpG oligonucleotides in various subcutaneous tumor models, ostensibly through macrophage/DC activation and increased expression of IL-12.” Page#11.

http://pharmacology.ucsd.edu/graduate/courseinfo/BIOM275-WI15-Courssens-Ruffell%20et%20al%20Cancer%20Cell%202014%20+%20supp.pdf

Some of the important information that has been covered in all of the articles referenced today has been:

CD8 T cells are critical for the control of viral infections. * Multiple cytokines influence every stage of the anti-viral CD8 T cell response. * Inflammation and certain chain cytokines enhance effector responses. * Different classes of chain cytokines promote immunological memory. * Immunosuppressive cytokines limit CD8 T cell responses and favor viral persistence.

If you notice from the previous diagram of Medscape, the blocking of IL-10R can be achieved by raising the levels of IL-12 directly within the cells and in return reduce the high amounts of IL-10. That’s the idea of ImmunoPulse IL-12 for making the tumor recognizable in order for CD8 T cells to do their job.
“IL-10 signaling to T cells reduces their proliferation and effector activity, including the production of effector cytokines such as IFN?. IL-10 can also indirectly inhibit T cell responses by decreasing the antigen presenting capacity of macrophages and DCs and reducing their expression of proinflammatory cytokines which amplify effector responses (Pestka et al., 2004; Wilson and Brooks, 2010). IL-10 deficient mice acutely infected with LCMV have greater numbers of virus-specific CD4 and CD8 T cells at the peak of the response ( Brooks et al., 2010 ), highlighting the role of this cytokine in restricting immune responses.”

However, the biological effects of IL-12 on CD8 T cell differentiation directly signal to the responding cells and act in conjunction with antigenic and costimulatory signals to promote the development and expansion of short-lived effector cells. CD8 T cells lacking the IL-12 inflammatory cytokine receptor are defective in the formation of short-lived cells. While the induction of IL-12 following infection boosts the expansion of highly cytolytic short-lived effector cells, curtailing the inflammatory conditions surrounding CD8 T cells still permits the formation of long-lived memory populations that operate to confer protection against re-exposure to the infection. Hence, there is the need to reduce the levels of IL-10.

"Anti-viral CD8 T cells and the cytokines that they love"
https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0042682212004539?returnurl=http:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0042682212004539%3Fshowall%3Dtrue&referrer=http:%2F%2Fwww.google.com%2Furl%3Fsa%3Dt%26rct%3Dj%26q%3D%26esrc%3Ds%26source%3Dweb%26cd%3D1%26ved%3D0CCIQFjAAahUKEwjwnt7d_NTIAhWCHD4KHZFAB9U%26url%3Dhttp%253A%252F%252Fwww.sciencedirect.com%252Fscience%252Farticle%252Fpii%252FS0042682212004539%26usg%3DAFQjCNHyJC93-oYmvDnPiY_9Q2GV2reT0w


Keep an open mind with the fact that in April 2011, Plexxikon was acquired by the Japanese pharmaceutical company Daiichi Sankyo for $805 million with an additional $130 m in potential milestone payments. There is very little to no reason for such big company not having a clue of the science that is needed. They probably approached Oncosec, but I know you will need the link. When I find it, if there is one, you will get it.