Cancer Moonshot - inmunoterapia

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Lun, 03 Abr 2017, 11:35

T cell pathways

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Mar, 04 Abr 2017, 00:04

Nanopartículas para administrar conjuntamente inhibidores de checkpoint con agonistas
Wang's group used a nanoparticle to combine a "red light" checkpoint inhibitor with a "green light" T-cell agonist that energizes the T-cells. This green light is an investigational OX40 agonist.

Wang's group attached them to a nanoparticle.

With the combined investigational nanoparticle treatment, the researchers reported improved stimulation of T-cells and better survival rates in preclinical models.

"We found that the therapeutic effect of nanoparticles is far better than the mixture of free agents"
http://www.news-medical.net/news/201704 ... ancer.aspx
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Mar, 04 Abr 2017, 00:10

Cancer de mama metastático triple negativo, primeros datos, responden 10-15% de los pacientes, pero casi todos respuestas largas (casi dos años)
The proportion of patients with metastatic triple-negative breast cancer who respond to the immunotherapy atezolizumab (Tecentriq, Genentech) is only 10% to 13%, but the responses tend to last a long time, according to new results from an ongoing phase 1 study.

The median duration of response was 21 months, which is "significant" in this setting

http://www.medscape.com/viewarticle/878125
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Mar, 04 Abr 2017, 00:33

Lipopolisacáridos similares a los encontrados en las células de algunas bacterias para calentar el sistema inmune
In a small sarcoma trial, signs of immune attack after injections of a bacteria-inspired drug

the experimental drug is a version of one component of a molecule, known as lipopolysaccharide, that is found in the cell walls of certain bacteria. Because lipopolysaccharide is not found in other organisms, its presence has been a red flag of infection to organisms for millions of years. Exposure to it, or certain components of it, triggers a strong, swift inflammatory response, which can set off a domino effect of defenses around the body

The researchers recruited 15 patients with metastatic, or far-flung, soft-tissue sarcomas who had a tumor that manifested just under their skin, where it could be injected. Almost all of the trial participants had already gone through prior cancer treatments that had failed them.
http://www.fredhutch.org/en/news/center ... fense.html
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Lun, 10 Abr 2017, 00:16

Inhibidores de checkpoint + virus del resfriado común para infectar el tumor y calentarlo. En melanoma
Half of patients with advanced melanoma responded to a novel combination treatment consisting of the common cold virus with an immune checkpoint inhibitor
The virus can directly infect many different cancer cells and boost adaptive and innate anticancer immune responses.

“About a week after the injection of the coxsackievirus there is pronounced infiltration of immune cells into the tumor deposit,” Curti said. “So a ‘cold’ tumor is now a much hotter tumor.”
Remarcablemente, también están respondiendo pacientes que ya habían estado en línea previa con inhibidor de checkpoint

http://www.rdmag.com/article/2017/04/co ... d-melanoma
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Mar, 11 Abr 2017, 23:30

Ovario, lecciones interesantes. Identificadas algunas proteínas específicas que pueden ser usadas como antígenos para crear CART
ovarian cancer cells overproduce two proteins - WT1 and mesothelin - and showed that T cells engineered to target them can kill mouse and human ovarian cancer cells in the laboratory.
El problema de CART en tumores sólidos es el microambiente: señales de inhibición, autodestricción y necesidad de glucosa
the problem of low sugar. To grow as rapidly as they do, ovarian cancer cells devour sugar, which they get from their environment.

However, the engineered T cells also need this sugar to fuel their journey to, and attack on, the cancer cells. The researchers at Fred Hutch are looking for a way to engineer the T cells so that they use a different source of energy
http://www.medicalnewstoday.com/articles/316763.php
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Mar, 11 Abr 2017, 23:36

MMR, primer marcador pantumoral que permitirá la aprobación de inhibidores de checkpoint en distintos tipos de tumor altos en inestabilidad de microsatélites. Es decir, se empiezan a regular los inhibidores de checkpoint no mediante tipo de tumor, sino mediante marcadores. Veremos que pasa con la carga mutagénica, y esperemos que vayan cayendo más cosas.

http://www.readcube.com/articles/10.103 ... rer=nature
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Mar, 11 Abr 2017, 23:40

Melanoma: el ratio entre el tamaño del tumor y la respuesta de células T predice quien está respondiendo (y permitirá modular la terapia sobre la marcha).
“The bigger the tumor, the more T cell ‘reinvigoration’ was needed by the drug. The ‘clinical failure’ that many patients experience was not solely due to an inability to spur the immune system, but rather resulted from an imbalance between the intensity of T-cell reinvigoration and initial tumor burden.”
Con un análisis de sangre se puede saber más sobre la respuesta esperada
the level of a particular protein made by these T cells was a useful predictor of the outcome to therapy, provided that doctors also took into account the amount of the patient’s cancer — essentially, the size and number of their tumors.
3 tipos causas distintas por las que los pacientes que no responden
it does not elicit a re-invigorated immune response
the immune effect is inadequate compared to the size of the tumor
the drug effect is off target.
https://www.pennmedicine.org/news/news- ... -tailoring

https://www.mskcc.org/blog/blood-will-t ... responders
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Mar, 11 Abr 2017, 23:47

PTEN, muchos años hablar de él, pero todavía no se sabe mucho...

https://www.mdanderson.org/publications ... erapy.html
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Sab, 15 Abr 2017, 03:05

Vacunas con neoantígenos en primera línea, inhibidores de checkpoint segunda línea.
Wu’s team sequenced the DNA from each patient’s tumors and used computational methods to predict mutations that coded for neoantigens. Then they made each patient a personal vaccine containing about 20 of these neoantigens. The researchers injected the vaccine under the patients’ skin periodically for 5 months. All are now cancer-free up to 32 months later.
2 pacientes recayeron. Segunda línea PD-1
When the two relapsed patients in Wu’s study received a PD-1 inhibitor, their new tumors vanished
Similar results come from an international trial using a vaccine developed by Ugur Sahin of University Medical Center of Johannes Gutenberg University in Mainz, Germany. The team injected RNA coding for up to 10 tumor neoantigens into the lymph nodes of 13 advanced melanoma patients whose tumors had been removed. Eleven remain cancer-free up to 26 months later, including two whose tumors reappeared, then shrank or were surgically removed, Sahin says. Another patient whose cancer returned received a PD-1 inhibitor and is also tumor-free.
http://www.sciencemag.org/news/2017/04/ ... ncer-check
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