OncoSec Medical Inc (ONCSQ)

[guti]

One can read from the information I previously posted as reference, that Tumor-Associated Macrophages (TAMs) are one of the major constituents of tumor stroma in many solid tumors and there is compelling preclinical and clinical evidence that macrophages promote cancer initiation and malignant progression. Therefore, these cells represent potential targets for therapeutic benefit. In addition to pro-inflammatory activity, in some instances, TAMs can play critical roles in antigen presentation and sustaining Th1 and cytotoxic T-cell responses through the production of IL-12. Unfortunately, in most clinically apparent tumors, there is little evidence of a large population of TAMs with macrophages programming. However, therapeutics, which can enhance these functional activities of macrophages (M1, M2) are a promising treatment strategy. Hence the need by Dr. Pierce to regulate Interleukin 12, which you can read more of the subject in the article “Positive Regulatory Role of IL-12 in Macrophages and Modulation by IFN-g1” which is published in The Journal of Immunology. http://www.jimmunol.org/content/167/1/221.full.pdf

Now, going back to my original post, which I can now take time to reference, https://blogs.shu.edu/cancer/2015/05/13/csf-1-inhibitor-plx3397-keytruda-anti-pd1-for-multiple-cancers/

One can see from the Medscape graph how low IL-12 relates to M2 macrophages by further reinforcing the M2 phenotype while suppressing CD8 + T cells, resulting in an overall immune-permissive environment for tumor growth and spread. Looking at the graph it shows why the need to regulate IL-12, since IL-12 is an interleukin that is naturally produced by macrophages. However, when a tumor is growing the Immune system does not recognize the need for IL-12 and in return drops their level due to the damaging loop that is taking place.

Dr. Pierce knows this and more, else, he would be talking out of his elbow when it comes to non-responders. And so would be Dr. Nghiem and Dr. Bhatia who only a few days ago at 2015 European Cancer Congress said “We believe this approach warrants further exploration in MCC, perhaps in combination with emerging systemic therapies, such as anti-PD-1/PD-L1 agents,” when referring to ImmunoPulse of IL-12 and Merkel Cell carcinoma.