Cancer Moonshot - inmunoterapia

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Mar, 21 Feb 2017, 13:38

Limitaciones de virus oncolíticos
Adenoviruses, which can cause colds, gasteroenteritis, and conjuctivitis — or pinkeye — can be genetically modified to infect cancer cells without affecting healthy cells.

The engineered virus works several ways. It kills cancer cells directly, it delivers therapeutic genes to cancer cells, and it promotes immune responses against tumor cells expressing a certain protein.

But a major pitfall of this approach is that the immune system sees the virus as an invader, so most T-cells go after the virus instead of cancer proteins. When the virus does manage to infect cancer cells, the T-cells fight only those cancer cells the virus has reached, leaving the remaining cancer cells unharmed.
What we are trying to do is redirect the immune system to attack the cancer cells instead of the virus
Anticuerpos biespecíficos

https://immuno-oncologynews.com/2017/02 ... st-tumors/
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Mié, 22 Feb 2017, 04:04

Return of the microbiota
Gut bacteria associated with cancer immunotherapy response in melanoma

Analysis of 113 fecal samples of patients with metastatic melanoma found that those who responded to a PD1 checkpoint inhibitor had a greater diversity of gut bacteria and larger volumes of a specific type of bacteria than those who did not respond.
"Our findings point to two potential impacts from additional research -- analyzing the diversity and composition of the microbiome to predict response to immunotherapy and modulating the gut microbiome to enhance treatment,"
Greater diversity of types of bacteria in the responders' microbiomes.
Increased abundance in responders of the Ruminococcaceae family of bacteria within the Clostridiales order.
Increased abundance of Bacteriodales in non-responders and a much lower diversity of bacteria.
https://eurekalert.org/pub_releases/201 ... 022117.php
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Jue, 23 Feb 2017, 01:44

CRISPR > CART
“These CRISPR-engineered CAR T cells seem to have an optimal level of functioning,” says Dr. Sadelain, who directs the Center for Cell Engineering at Memorial Sloan Kettering. “They retain their ability to kill tumor cells for much longer than conventional CAR T cells, which tend to burn out more quickly.”
https://www.mskcc.org/blog/crispr-genom ... next-level
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Jue, 23 Feb 2017, 01:50

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Vie, 24 Feb 2017, 00:22

Interferón gamma
Preliminary Results Show Interferon-Gamma Holds Promise in Making Immunotherapy a More Effective Cancer Treatment

“The early indication is that adding this cytokine to the immunotherapy treatment does demonstrate some changes in the peripheral immune environment that may impact the effectiveness of immune checkpoint blockade,” Zibelman said. “Our work is ongoing, but the first data are encouraging.”
https://www.foxchase.org/blog/2017-02-2 ... -Treatment
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Vie, 24 Feb 2017, 02:25

Lo que viene...

Imagen
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Sab, 25 Feb 2017, 02:38

Vacuna de células dendríticas
preventive dendritic cell vaccination is safe and can elicit immune responses without provoking autoimmunity. Initial research performed in three patients with colorectal cancer who also carry Lynch revealed that dendritic cell vaccination using frameshift-derived neopeptides within TGF-bRII and caspase-5, along with a peptide within carcinoembryonic antigen typically expressed by colon cancers, greatly increased the number of vaccine-specific CD8+ T cells targeting these protein fragments.

This vaccination approach is now being tried in 20 cancer-free individuals who carry Lynch to see how well the dendritic cells can prevent colorectal cancer development. Of the 20 patients, the worst adverse event observed thus far has been grade 4 fever in one individual. Mutated neoantigen-specific T cells were detected in all patients tested (13 of 20). Patient follow-up is ongoing.
Jarro de agua
many tumor-associated antigens, particularly those that are overexpressed or modified post-translation, are also found in nonmalignant diseased tissues, which has broad implications for immunotherapy.
http://immunosym.org/daily-news/researc ... r-vaccines
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Sab, 25 Feb 2017, 02:45

Encuentran dos fenotipos de células T de entre unas 5000 distintas, que son especialmente efectivas encontrando y combatiendo células cancerígenas. Actualmente se está evaluando expandir las células T en conjunto ex vivo (CART), la idea que surge de aquí es que quizás expandiendo solo estas super células T exista mayor eficacia tratando el cáncer.

Han etiquetado las distintas células y su destino in vivo y lo que hacen en el organismo de pacientes con cancer
The tech was developed by Seattle-based Adaptive Biotechnologies, and it assigns a “barcode” to each T-cell based on the kind of T-cell receptor (TCR) it has. This allows researchers to track different kinds of T-cells in the lab and in patients’ bodies.
researchers were able to identify a set of cells that appear to be particulalry effective against cancer.
Características: son jóvenes, resistentes y localizan bien a sus presas
First, they all appear to be young T-cells, which means they “have a huge potential to proliferate and survive in the face of large quantities of antigen,” she said. In other words, the cells will continue to multiply and resist being worn out even after repeatedly attacking cancer cells.
Second, Chapuis said they may have a TCR that is particularly good at finding cancer cells. That means even after most of the cancer cells have been destroyed, they can “still seek-out [sic] the tumor left behind and get rid of it,”
http://www.geekwire.com/2017/fred-hutch ... ng-cancer/

http://immunology.sciencemag.org/content/2/8/eaal2568
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Sab, 25 Feb 2017, 02:48

Encuentran la proteína BIM en las células T, que correlaciona con la respuesta a la inmunoterapia. Un posible candidato a biomarcador.

http://www.cancerresearch.org/news-publ ... -treatment
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Sab, 25 Feb 2017, 14:53

Resistencia a inmunoterapia por mutaciones que conducen a una menor expresión de neoantígenos
PTEN mutations and reduced expression of genes encoding neoantigens as potential mediators of resistance to immune checkpoint therapy.
cell.com/immunity/fulltext/S1074-7613(17)30034-1
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