Cancer Moonshot - inmunoterapia

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Fisio
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Lun, 06 Mar 2017, 01:59

Nueva citoquina posible para el pipeline LIGHT
LIGHT is an immune-stimulating chemical messenger previously found to have low levels of expression in patients with colon cancer metastases
mice were randomized into two groups—one group had the cytokine LIGHT turned on in the tumors, and the other served as a control group for comparison.

Tumors exposed to LIGHT showed an influx of T-cells that resulted in rapid and sustained diminishment in size, even after expression of the cytokine stopped. In mice with liver metastases, expression of LIGHT similarly provoked a potent immune response that resulted in a significant decrease in tumor burden
https://news.uic.edu/scientists-stimula ... cer-growth
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Lun, 06 Mar 2017, 02:03

Vacunas usando ADN sintético modificado para ser reconocido como extraño
most vaccines targeting tumor-associated antigens have had limited success so far in producing therapeutic effects against most cancers due to poor immunogenicity. Despite being specific for tumor cells, tumor-associated antigens typically trigger weak immune responses because they are recognized as self-antigens and the body has in place natural mechanisms of immune acceptance, or "tolerance," that prevent autoimmunity but also limit the efficacy of cancer vaccines.
DNA vaccine using a synthetic DNA sequence for WT1 that, while maintaining a very high homology with the native sequence, contains new changed sequences that differ from native WT1 in an effort to render it more recognizable by the host immune system. This study shows that this novel vaccine design was able to induce WT1-specific, robust T cell responses as well as antibody production with no apparent toxicity both in mice and in non-human primates. The novel WT1 vaccine was superior to a more traditional native WT1 vaccine because it was able to break immune tolerance and induce long term immune memory
https://www.sciencedaily.com/releases/2 ... 121759.htm
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Lun, 06 Mar 2017, 02:23

NIH: que son los inhibidores de checkpoint?
Checkpoint inhibitors, all of which are monoclonal antibodies , are typically given over a period of one hour, every 2 to 3 weeks
it's also really important to understand that immune checkpoint inhibitors are not directed against the tumor. They have no direct antitumor activity, so if there is no underlying immune response against a tumor prior to using these drugs they won’t have any effect. They only take the brakes off of the immune response if you already have some type of immune response to begin with.
mutagenicidad
One possible way to get that underlying response is if there are many mutations in the tumor. Certain tumors—lung, melanoma, bladder—are more likely to have many mutations and so seem to be more likely to generate an immune response.
The majority of responses we see with these drugs are still partial responses, at rates similar to what we see with chemotherapy and other targeted agents. But often the responses we see are very deep, 80 to 90 percent tumor shrinkage.

The more important thing—and the thing that’s blown everybody away—is how durable the responses are. Even the partial responses are very durable, compared with what we’re used to seeing with chemotherapy or targeted therapies like tyrosine kinase inhibitors.
https://www.cancer.gov/news-events/canc ... checkpoint
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Lun, 06 Mar 2017, 02:31

IFI16 > STING > interferón > respuesta inmune
Researchers have identified an enzyme called IFI16 whose expression is key for immune cells to detect danger and initiate an immune response
They found that macrophages needed IFI16 to activate STING, which in turn would activate the immune sensing and signaling when DNA challenges promote interferon production and a general immune response.

They found that macrophages needed IFI16 to activate STING, which in turn would activate the immune sensing and signaling when DNA challenges promote interferon production and a general immune response.
https://immuno-oncologynews.com/2017/03 ... pathogens/
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Lun, 06 Mar 2017, 02:39

Al menos 7 virus implicados en el 10-15% de los canceres
There are at least 7 viruses implicated in the pathogenesis of 10% to 15% of all human cancers worldwide. Despite a high prevalence of infection with these viruses, only a minority of infected individuals develop a subsequent malignant tumor, underscoring the important role that host and environmental factors have in cancer development
http://jamanetwork.com/journals/jamaonc ... ct/2578708
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Lun, 06 Mar 2017, 16:31

Cancer de pancreas, malas perspectivas: camino de ser la segunda causa de muerte por cancer. Lo curioso es que el cancer de pancreas genera una barrera física fibrótica para que el sistema inmune no pueda acceder a él.
pancreatic cancer is the 4th to 5th most common cause of cancer death in the UK & US, and is predicted to be the second commonest cause by 2020
pancreatic cancer has remained largely refractory to immunotherapy, including immune checkpoint inhibitors
FAK
Focal Adhesion Kinase (FAK), can sensitise genetically engineered mouse (GEM) models of pancreatic cancer to the anti-tumour effects of immune checkpoint blockade [3]. They show that this synergistic activity is underpinned by reprogramming of the fibrotic and immuno-suppressive pancreatic tumour microenvironment (TME)

FAK inhibition reduces collagen deposition within the tumour environment, overcoming a physical barrier to T-cell infiltration
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319091/
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Lun, 06 Mar 2017, 16:33

1100 fármacos inmunológicos estudiados en este momento. Más del doble que hace 2 años.

https://www.wsj.com/articles/race-tight ... 0?mod=e2tw
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Lun, 06 Mar 2017, 16:50

DGK
DGK-inhibition has promising feature for cancer immunotherapy on multiple levels, re-invigorating T and NK cells for tumor cell attack, possibly making them resistant to TGF-ß suppression, and also weakening tumor cells directly. As DGKs and co-inhibitory surface proteins (PD-1, CTLA-4) control different steps in the signaling cascade, it is expected that DGK-inhibition will combine beneficially with current checkpoint blockade therapies or other immunotherapies
http://journal.frontiersin.org/article/ ... 00016/full

NK cells
In some tumor types, such as RCC, they appear to play a prominent role as their number is predictive of good prognosis while that of CD8-T cells is not
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Lun, 06 Mar 2017, 17:04

Bifidobacteria tan eficaz como fármacos inmunoterápicos
Gut bacteria can dramatically amplify cancer immunotherapy

By introducing a particular strain of bacteria into the digestive tracts of mice with melanoma, researchers at the University of Chicago were able to boost the ability of the animal’s immune systems to attack tumor cells. The gains were comparable to treatment with anti-cancer drugs known as checkpoint inhibitors, such as anti-PD-L1 antibodies.
Tremendamente curioso
They noticed that mice purchased from Jackson Laboratory (JAX) tended to have a robust spontaneous immune response to small melanoma tumors implanted under their skin. Mice from Taconic Biosciences (TAC) showed only a weak immune response.

But when the researchers put the mice from both sources in cages together for three weeks, they found that co-housing “completely abolished the differences in tumor growth,” Gajewski said. This made them suspect that by sharing exposure to various types of bacteria, the TAC mice had acquired microbes from JAX mice that somehow enhanced their immunity to tumors
http://science.sciencemag.org/content/e ... ce.aac4255

En fin, una pena que no se investigue más esto...
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Mar, 07 Mar 2017, 01:10

Ensayos clínicos en cánceres raros, definidos como aquellos con una incidencia < 6 casos por 100.000 (que son nada menos que el 20% de los casos de cancer, ojo). Suerte a todos.
It’s the first federally funded immunotherapy trial devoted to rare cancers
DART, which stands for dual anti–CTLA-4 (cytotoxic T-lymphocyte–associated protein 4) and anti–PD-1 (programmed cell death protein 1) blockade in rare tumors. It is managed by SWOG, the cancer clinical trials group that is part of the National Cancer Institute’s (NCI) National Clinical Trials Network.
http://www.ascopost.com/issues/february ... =hootsuite
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