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Re: low response rates...

There’s evidence that one of the causes of low immune response and TIL suppression is a result of ATP conversion to adenosine… ATP is released by dying cells in the tumor environment are converted to adenosine… adenosine has been shown to be a suppressor of immune response.

There are an increasing # of bio's that are targeting adenosine by blocking CD73/CD39/A2a which has been shown to enhance T cell immune response. There are 12 drugs currently in pre-clinical testing or in the clinic from the following...

Innate Pharma, Domain Tx/Kaldi, BMY, Corvus, AZN/Medimmune, AZN/Heptares, NVS/Palobiofarm and Arcus who just raised $120M a few days ago...

Stealthy Arcus emerges with $120M to make personalized I/O therapy a reality
http://www.fiercebiotech.com/biotech/exclusive-stealthy-arcus-emerges-120m-to-make-personalized-i-o-therapy-a-reality

“Immuno-oncology is a very unique, rare situation,” said Arcus’ Rosen. “The body should be able to kill tumors, but the reality is that most things tried in the past haven’t worked so well.”
He continued, “Recent trials with immune checkpoint inhibitors, such as PD-1 antibodies, have shown that if you can get the immune system to do what it’s supposed to do, you can treat cancer.

The company has selected its first three targets for small molecules along the ATP-adenosine pathway; CD73, CD39 and the A2A receptor. The idea is to use multiple means to discourage the extracellular enzymatic conversion of ATP, which is released by damaged or dying cells, into adenosine; the former encourages an immune response to cancer cells while the latter discourages it.

“Normally, ATP is released by cells as they die or are damaged,” explained Rosen. “It’s a signal to the rest of the immune system to mount an inflammatory response. But ATP is converted to adenosine and by converting ATP to adenosine, not only is the signal to mount an immune response reduced, but adenosine also tells the immune system to stand down.”

Some supporting studies...

Extracellular adenosine triphosphate and adenosine in cancer.
http://www.ncbi.nlm.nih.gov/pubmed/20661219

Adenosine triphosphate (ATP) is actively released in the extracellular environment in response to tissue damage and cellular stress. Through the activation of P2X and P2Y receptors, extracellular ATP enhances tissue repair, promotes the recruitment of immune phagocytes and dendritic cells, and acts as a co-activator of NLR family, pyrin domain-containing 3 (NLRP3) inflammasomes. The conversion of extracellular ATP to adenosine, in contrast, essentially through the enzymatic activity of the ecto-nucleotidases CD39 and CD73, acts as a negative-feedback mechanism to prevent excessive immune responses.

Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review).
http://www.ncbi.nlm.nih.gov/pubmed/18292929

It is well established that extracellular adenosine inhibits T lymphocyte activation and effector function, including T cell adhesion to tumor cells and cytotoxic activity, by signaling primarily through A2a and A3 adenosine receptors on the surface of T cells. Importantly, A2a adenosine receptor-deficient mice exhibit enhanced anti-tumor immune responses by CD8+ T cells, as well as a dramatic reduction in the growth of experimental tumors in comparison to wild-type controls. A2a adenosine receptor signaling has also been implicated in adenosine-mediated inhibition of cytokine production and cytotoxic activity by activated natural killer (NK) cells,

Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors.
http://www.ncbi.nlm.nih.gov/pubmed/23964122

CD73 inhibits antitumor immunity through the activation of adenosine receptors expressed on multiple immune subsets. CD73 also enhances tumor metastasis, although the nature of the immune subsets and adenosine receptor subtypes involved in this process are largely unknown.

Furthermore, our data strongly suggest that A2A or A2B antagonists may be useful for the treatment of metastatic disease. Overall, our study has potential therapeutic implications given that A2A/A2B receptor antagonists have already entered clinical trials in other therapeutic settings.