Cancer Moonshot - inmunoterapia

Foro general ciencia, medicina, nutrición, salud pública, política

Moderador: Fisio

Responder
Avatar de Usuario
Fisio
Administrador del Sitio
Mensajes: 6736
Registrado: Dom, 01 Sep 2013, 14:18
Ubicación: Madrid
Contactar:

Vie, 17 Feb 2017, 01:13

Virus oncolíticos + inhibidores de checkpoint intratumoral en distintos tumores sólidos, programada fase 2 en 60 pacientes.
“We hope this novel ‘in situ immunization’ strategy will overcome the resistance to cancer immunotherapy that we observe in many patients.”

Pexa-Vec, derived from the term pexastimogene devacirepvec, is an oncolytic virus designed to kill cancer cells using three mechanisms. It triggers the breakdown of cancer cells through viral replication. It promotes disruption of blood vessels, reducing the tumor’s blood supply. And the GM-CSF gene it contains attracts immune cells to tumors and stimulates strong anti-tumoral responses.
https://immuno-oncologynews.com/2017/02 ... t-patient/
Avatar de Usuario
Fisio
Administrador del Sitio
Mensajes: 6736
Registrado: Dom, 01 Sep 2013, 14:18
Ubicación: Madrid
Contactar:

Vie, 17 Feb 2017, 01:51

The process of T cell activation involves antigen presentation by the major histocompatibility complex (MHC) molecules on the antigen-presenting cells (APCs) to the corresponding T cell receptor (TCR) on naive T cells.
the intrinsic genomic instability common to all cancers facilitates the escape from cytotoxic or targeted therapies

host immune responses and tumor genomics are tightly related, as illustrated by the notion that neoantigens arising from genomic mutations may shape immune responses (Schumacher and Schreiber, 2015); however, these responses may prove ineffective against a heterogeneous and evolving tumor microenvironment.
15 años desde ratones a humanos...
CTLA-4 blocking antibodies could treat tumors in immune competent animal models (Leach et al., 1996).
Cell-based immunotherapy was pioneered by many investigators, including Alex Fefer, Phil Greenberg, Zelig Eshhar, Steven Rosenberg, and colleagues in the 1980s, inspired by the correlation of the number of tumor infiltrating lymphocytes (TILs) and survival in some cancers. This process required TILs to be isolated from the patient’s surgical specimen, expanded in vitro, and re-infused back to the lymphocyte-depleted patient.
cell.com/cell/fulltext/S0092-8674(17)30065-X
Avatar de Usuario
Fisio
Administrador del Sitio
Mensajes: 6736
Registrado: Dom, 01 Sep 2013, 14:18
Ubicación: Madrid
Contactar:

Sab, 18 Feb 2017, 00:04

“Instead of poisoning the cancer cell, we are letting the immune system directly kill it.”

By 2008, the first clinical trial of a PD-L1 blocking drug had begun. In 2013, Science magazine dubbed this form of immunotherapy the “Breakthrough of the Year.” And by the end of 2014, about a dozen PD-L1 blocker trials had been completed with about 50 more trials underway.
Avatar de Usuario
Fisio
Administrador del Sitio
Mensajes: 6736
Registrado: Dom, 01 Sep 2013, 14:18
Ubicación: Madrid
Contactar:

Lun, 20 Feb 2017, 02:23

VEGF, no solo angiogénesis, también es inmunosupresora
a protein called vascular endothelial growth factor (VEGF)—which most people think of as being responsible for forming new blood vessels to feed tumors—also has direct effects on shutting down the immune system in tumors.

The concept of the trial is basically to use a VEGF blocker to sort of prime the tumor environment and hopefully get immune cells into the tumor, and then use the checkpoint inhibitor to turn them on
http://ht.ly/YgIo3096OZT
Avatar de Usuario
Fisio
Administrador del Sitio
Mensajes: 6736
Registrado: Dom, 01 Sep 2013, 14:18
Ubicación: Madrid
Contactar:

Lun, 20 Feb 2017, 02:27

Sistema inmune innato vs adptativo
The number of infiltrating adaptive immune system cells with tumour-rejecting capacity, primarily T lymphocytes, is not particularly high in breast cancer compared with other cancer types, but infiltration occurs in a large proportion of cases. There is strong evidence demonstrating the importance of the immunosuppressive role of the innate immune system during breast cancer progression
https://www.ncbi.nlm.nih.gov/pubmed/28193698
Avatar de Usuario
Fisio
Administrador del Sitio
Mensajes: 6736
Registrado: Dom, 01 Sep 2013, 14:18
Ubicación: Madrid
Contactar:

Lun, 20 Feb 2017, 02:28

Al menos 7 virus causan el 15% de cancer

http://jamanetwork.com/journals/jamaonc ... ct/2578708
Avatar de Usuario
Fisio
Administrador del Sitio
Mensajes: 6736
Registrado: Dom, 01 Sep 2013, 14:18
Ubicación: Madrid
Contactar:

Lun, 20 Feb 2017, 02:43

Patient-specific candidate neoantigens may be computationally predicted on the basis of the mutations found in the respective tumor. However, only a very small number of candidate neoantigens seem to evoke an immune response in patients. In fact, of the hundreds of mutations identified in, for example, melanoma that could provide a wealth of T-cel targets, only a few (between two and five) have been found to be successful in producing neoantigen-specific T cells, which can be identified among tumor-infiltrating lymphocytes.
Lo mismo en sangre.

Las células T de personas con cancer responden a menos neoantígenos que las personas sanas (respuesta a 2 vs 11)

http://www.nejm.org/doi/full/10.1056/NE ... ts.twitter
Avatar de Usuario
Fisio
Administrador del Sitio
Mensajes: 6736
Registrado: Dom, 01 Sep 2013, 14:18
Ubicación: Madrid
Contactar:

Mar, 21 Feb 2017, 13:18

Vacuna con bacterias usada desde hace 30 años en cácer de vejiga
Bacillus Calmette-Guérin Immunotherapy for Bladder Cancer Overview of BCG Immunotherapy

BCG supplanted cystectomy as the treatment of choice for CIS in the mid-1980s. Studies have consistently shown that BCG treatment can eradicate this cancer in 70% of patients with CIS who meet these criteria. To prevent cancer recurrence, long-term maintenance therapy following the induction phase is necessary
http://emedicine.medscape.com/article/1950803-overview
Avatar de Usuario
Fisio
Administrador del Sitio
Mensajes: 6736
Registrado: Dom, 01 Sep 2013, 14:18
Ubicación: Madrid
Contactar:

Mar, 21 Feb 2017, 13:24

Activando y expandiendo células T...
In a two-step process, the team exposed the T cells to cancer-related proteins, which activated innate immunity. They also replicated signals that normally occur in the body when a serious infection is present—alarm bells, if you will, that awaken resting T-cells and prompt them to multiply.

“Our method strictly employs natural signals to activate the immune blood cells outside the body,” said Nora Disis, M.D., a University of Washington immunotherapist. “This gives rise to expanded armies of T cells, which specifically recognize proteins that are present on cancer cells and which can be reinfused into patients for therapeutic evaluations in future clinical trials.”

They studied the culture method’s ability to produce T-cell responses against the proteins MUC1, HER2/neu and CMVpp65. MUC1 is expressed in multiple cancers, including breast, pancreatic and lung, among others. HER2/neu is present in as many as half of a range of cancers and CMVpp65 is expressed by half of primary brain tumors, according to the statement.

The researchers found that it took three weeks to raise “natural T-cell armies” trained to recognize cancers that express these proteins. And they’re not stopping here: the team thinks the method could be applied to other proteins that are present on cancer cells.
http://www.fiercebiotech.com/research/n ... le-cancers
Avatar de Usuario
Fisio
Administrador del Sitio
Mensajes: 6736
Registrado: Dom, 01 Sep 2013, 14:18
Ubicación: Madrid
Contactar:

Mar, 21 Feb 2017, 13:28

Cancer de ano de células escamosas. 25% responden...
Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 stud

Among the 37 patients, nine (24% [95% CI 15–33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported.
Interpretation

To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease.
thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30104-3/fulltext
Responder