Cancer Moonshot - inmunoterapia

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Lun, 13 Feb 2017, 02:54

Telomerasa como objetivo de vacunas
Jane Lebkowski of Asterias finished the day with a talk on an autologous telomerase-based DC vaccine (AST-VAC1); telomerase is considered a hallmark of cancer and thus a natural target. To produce the vaccine, DCs are harvested via leukapheresis, matured, electroporated with human telomerase reverse transcriptase (hTERT) mRNA, and cryopreserved. Including a LAMP sequence stimulates helper and cytotoxic T cells through HLA class I and II pathways. In an initial prostate cancer trial, the vaccine decreased tumor-cell doubling time. In subsequent trials in AML it prevented relapse, and AML patients in complete remission who received the vaccine had considerably improved overall survival.
http://www.nyas.org/Publications/Ebrief ... c69a4a1a9d
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Lun, 13 Feb 2017, 03:03

Me ha gustado esta entrevista
Checkpoint inhibitors, all of which are monoclonal antibodies , are typically given over a period of one hour, every 2 to 3 weeks.

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

Certain tumors—lung, melanoma, bladder—are more likely to have many mutations and so seem to be more likely to generate an immune response.

In most patients with colorectal cancer, for example, we really don’t see strong immune activity. However, we now know that if colorectal tumors have something called microsatellite instability, which produces many mutations, there is increased immune recognition of the tumor. That's where we have seen checkpoint inhibition work in patients with colorectal cancer.

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.

What we are seeing in some cases are functional cures

If we see inflammation, then maybe we can treat with the checkpoint inhibitor. If we don’t see it, perhaps we can add a therapy that can cause an immune response at the tumor site and then follow up with a checkpoint inhibitor.
https://www.cancer.gov/news-events/canc ... checkpoint
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Lun, 13 Feb 2017, 22:11

Cancer de páncreas, back to basics: IL10
AM0010, a pegylated form of IL-10, stimulates an immune response by inducing the activation and proliferation of tumor-specific CD8-positive T cells, resulting in an antitumor immune memory, researchers have reported.1 Its mechanism of action is distinct from and complementary to the PD-1/PD-L1 checkpoint blockade antibodies that are rapidly gaining adoption in a wide range of cancer types - See more at: http://www.onclive.com/publications/onc ... gXm3k.dpuf

“If the trial is positive, this would be the first immunotherapy option for patients with pancreatic cancer.”
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Lun, 13 Feb 2017, 22:13

MCRC con MSI (15-20% total CRC). Un paciente de cada 20 puede tener un beneficio profundo. Así es como va a ir avanzando esto... de subtipo en subtipo
The overall response rate in these patients was 31.1 percent, the 12-month progression-free survival rate was 48.4 percent, and the 12-month overall survival rate was 73.8 percent. Results are not yet available for the cohort of patients with MSI-H mCRC who are receiving Opdivo plus Yervoy
http://www.curetoday.com/articles/exper ... py-for-crc
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Mié, 15 Feb 2017, 01:08

Algunos pacientes que no toleran la inmunoterapia experimentan sus beneficios aunque se interrumpa el tratamiento
“This study is welcome news for patients who are unable to continue immunotherapy as a result of adverse effects,”. More broadly, these findings call into question the current standard of continuous treatment with immunotherapy, though longer term follow-up of patients is needed.”
Among patients with advanced kidney cancer who stopped PD1/PD-L1 immunotherapy early due to side effects, 42% had a durable response, meaning they were able to remain off additional systemic therapy for 6 months or more
http://www.asco.org/about-asco/press-ce ... even-after
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Mié, 15 Feb 2017, 01:11

PDL1 inducido por TNF-a local en el microambiente tumoral
immature bone marrow monocytes in tumor-bearing mice had low levels of PD-L1 expression, while higher levels of expression were observed on monocytes in circulation. In contrast, macrophages found in tumor tissues expressed much higher levels of PD-L1 than circulating monocytes, implying upregulation by the tumor microenvironment. We demonstrated that tumor-conditioned media strongly induced increased PD-L1 expression by bone marrow-derived monocytes and TNF-α to be a cytokine that causes an upregulation of PD-L1 expression by the monocytes
https://www.ncbi.nlm.nih.gov/pubmed/28184968
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Mié, 15 Feb 2017, 01:13

Más microbiota: los antibióticos empeoran (mucho posiblemente) la respuesta a la inmunoterapia
Immunotherapy may be less effective in patients who receive antibiotics less than a month before starting treatment. In the study, cancer worsened more quickly in such patients than in those who did not receive antibiotics (median progression-free survival 2.3 months vs. 8.1 months).
http://www.asco.org/about-asco/press-ce ... s-efficacy
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Mié, 15 Feb 2017, 01:17

Vinay Prasad dando hostias como panes...
Exceptional or super responders to cancer drugs have been described in the literature; however, there is incompleteness in the reporting of relevant data that may help clarify whether such responses are secondary to treatment or reflect underlying biology
https://www.ncbi.nlm.nih.gov/pubmed/265 ... olding=npg
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Vie, 17 Feb 2017, 00:44

type I interferon receptor IFNAR1, which is activated by interferon, a molecule that is known to fight cancers and is itself a treatment for cancer, infections and other conditions. When a tumor forms, the hypoxic environment of its fast-growing mass leads to a reduction in levels of the interferon receptor on T cells. This reduction precipitates the T cells’ demise, thus creating an environment where cancer cells can survive and reproduce unchecked.

“We found that this downregulation of the receptor is required for the generation of immune-privileged niches in the tumor microenvironment. This decreases the efficacy of immune therapies. So, if we can reverse that, then we’ll probably improve the outcome of treatment.”
https://news.upenn.edu/news/penn-vet-st ... unotherapy
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Vie, 17 Feb 2017, 00:46

Nueva era... número de ensayos clínicos con CAR

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http://celltrials.info/2017/02/10/car-cell-trend/
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