Scientists have discovered an important gene whose loss lies behind follicular lymphoma, an incurable cancer

Follicular lymphoma is an incurable cancer that affects over 200,000 people worldwide every year. A form of non-Hodgkin lymphoma, follicular lymphoma develops when the body starts making abnormal B-cells, which are white blood cells that in normal conditions fight infections. This cancer is associated with several alterations of the cell’s DNA, but it has been unclear which gene or genes are involved in its development. EPFL scientists have now analyzed the genomes of more than 200 patients with follicular lymphoma, and they discover that a gene, Sestrin1, is frequently missing or malfunctioning in FL patients. The discovery opens to new treatment options and it is now published in Science Translational Medicine.

One of the common features of follicular lymphoma is a genetic abnormality between two chromosomes (14 and 18). In an event known as “chromosomal translocation” the two chromosomes “swap” certain parts with each other. This triggers the activation of a gene that protects cells from dying, making cells virtually immortal — the hallmark of a tumor.

Moreover, approximately 30% of follicular lymphoma patients lose also a portion of chromosome 6, affecting multiple genes involved in suppressing the emergence of a tumor. These patients typically have poor prognosis. Another 20 % of patients have alterations causing chromosomal disorganization and the consequent malfunctioning of several genes and proteins. The bottom line is that for both group of patients it is very difficult to pinpoint which of all the affected genes are actually causing the disease.

The lab of Elisa Oricchio at EPFL, with colleagues from the US and Canada, analyzed the genomes of over 200 follicular lymphoma patients. Their analyses revealed that a specific gene, Sestrin1, can be harmed by both loss of chromosome 6 and silenced in patients.

Sestrin1 helps the cell defending itself against DNA damage — for example after exposure to radiation — and oxidative stress. In fact, Sestrin1 is part of the cell’s anti-tumor mechanism that stops potentially cancerous cells from growing.

Disruption of a region in chromosome 6 or epigenetic modifications of the DNA block Sestrin1 expression and these contribute to the development of Follicular Lymphoma.

Beyond identifying the Sestrin1 gene as frequently altered in FL patients, the scientists demonstrated that Sestrin1 is able to suppress tumors in vivo. They showed that Sestrin1 exerts its anti-tumor effects by blocking the activity of a protein complex called mTORC1, which is well known for controlling protein synthesis as well as acting as a sensor for nutrient or energy changes in the cell.

Finally, the identification of loss of Sestrin1 as a key event behind the development of follicular lymphoma is particular important because it helps identifying patients that will benefit from new therapies.Indeed, this study shows that the therapeutic efficacy of a new drug that is currently in clinical trial depends on Sestrin1. Importantly, this dependency can be extended beyond follicular lymphoma to other tumor types.

Source: https://www.sciencedaily.com/releases/2017/06/170628144909.htm

wmay13241

 

Advertisements

CAR-T news — June 2017

“One of the leading CAR T-cells immunotherapy company, Cellectis dosed the first blood cancer patient with the allogeneic, “off-the-shelf” CAR-T therapy, UCART123 at Weill Cornell Medicine and NewYork-Presbyterian Hospital…”

Scientists Get Closer to First CAR T-Cells Based Immunotherapy for Humans

Cellectis’ off-the-shelf CAR-T Cancer Therapy has Entered the Clinic

Cellectis’ Press Release…

First in Human Administration of UCART123 in Cellectis’ AML Phase I Clinical Trial at Weill Cornell Medicine, NewYork-Presbyterian Hospital | Cellectis


A journalist from Bloomberg News is working on a story similar to the one below:

For experimental cancer therapy, a struggle to ensure supply keeps up with demand | Science | AAAS


“The sky-high cost of producing CAR T cells, and limitations on the availability and regulatory qualification of reagents can be barriers to making CAR T cell therapy accessible…”

Biotechin.Asia- Driving CAR T-Cell Therapy From Bench to Bedside

CAR-T Value Calculation In The Firing Line | Seeking Alpha


Work continues on applying CAR-T to solid tumors:

Unleashing CAR-T Therapies on Solid Tumors: Are We There Yet? | BIOtechNow

Buy Celyad And Get In On The CAR-T Space In Solid Tumors: Medicine’s Next Frontier – Celyad (NASDAQ:CYAD) | Seeking Alpha


A history of all reported deaths (clinically described as a “Grade 5 Adverse Event”) thus far from CAR-T:

EP Vantage – Spotlight – Putting a number on CAR-T deaths


Neurotoxicity needs separate treatment from CRS in CAR T-cell therapy  | (Free registration required)


Engineering CAR-T cells


CAR-T coverage in PC Magazine(!)

How Scientists Are Hacking Cancer | News & Opinion | PCMag.com

Checking These Areas for Lumps Can Help Catch Lymphoma Early

lymphomanewstoday.com
This video from TakeaPITStop uses a Barbie doll to demonstrate how lymphoma patients often discover their lumps.

 

This video from uses a Barbie doll to demonstrate how lymphoma patients often discover their lumps. During Barbie’s usual beauty routine of shaving, moisturizing and applying fake tan she notices a lump near her collarbone.
 
Although she thought it could be just a cyst she decides to get it checked out by her doctor and after several tests, she’s diagnosed with Hodgkin’s lymphoma. The video goes on to detail some of the common symptoms of the disease including fatigue, persistent lumps in the neck, armpits or groin, intensive itching, and night sweats. It explains that lymphoma is the most common cancer in people under the age of 30 and advises young people to check their neck, armpits, and groin regularly for any lumps and get anything unusual checked out by their doctor.
wmay13241

CD19-CAR T Cell Therapy Can Effectively Treat Non-Hodgkin’s Lymphoma

Recently, scientists at the University of Pennsylvania and Novartis reported that CD-19-CAR T cell therapy got the expected results in an early CD19 CAR-T preclinical assay involving 43 patients with non-Hodgkin’s lymphoma. These subjects were all patients with chemotherapy failure and expected survival of only about 3 months. These chemotherapy regimens include Rituximab, an antibody (first-line therapy) with B-cell antigen CD20 as the drug target. However, only 30 of the 43 subjects were successfully administered, and other patients failed to receive CD19-CAR T cell therapy due to CAR-T cell preparation failure. Among the patients successfully treated, 15 were diffuse large B cell lymphoma, 13 were follicular lymphoma, and 2 were mantle cell lymphoma.

At present the clinical trial has been carried out for about two years, and the total response rate is 47%. Six of the patients have got completely remission, and one of them did not be seen tumor recurrence in 14 months of observation. The CD19 CAR T cell therapy was most effective in follicular lymphoma with a response rate of 73%. Side effects were also expected, with only one case of lethal encephalitis, and the primary side effects were cytokine release storm (but mostly one to two level) and reversible nervous system toxicity.

Full article: http://www.digitaljournal.com/pr/3395226

The gene behind follicular lymphoma

Follicular lymphoma is an incurable cancer that affects over 200,000 people worldwide every year. A form of non-Hodgkin lymphoma, follicular lymphoma develops when the body starts making abnormal B-cells, which are white blood cells that in normal conditions fight infections. This cancer is associated with several alterations of the cell’s DNA, but it has been unclear which gene or genes are involved in its development. EPFL scientists have now analyzed the genomes of more than 200 patients with follicular lymphoma, and they discover that a gene, Sestrin1, is frequently missing or malfunctioning in FL patients. The discovery opens to new treatment options and it is now published in Science Translational Medicine.

Read more at: https://medicalxpress.com/news/2017-06-gene-follicular-lymphoma.html#jCp

wmay13241

VIDEO: CD19–directed CAR T cells shows promise in advanced lymphomas

Treatment with JCAR017 showed promise in patients with heavily pretreated relapsed or refractory diffuse large B-cell lymphoma, according to the phase 1 TRANSCEND NHL trial presented at the ASCO Annual Meeting, June 2017.

Jeremy Slade Abramson, MD, clinical director of the Center for Lymphoma at Massachusetts General Hospital Cancer Center, and colleagues evaluated the safety and efficacy of JCAR017 (Juno Therapeutics) in 28 patients with relapsed or refractory diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, grade 3B follicular lymphoma or mantle cell lymphoma.

Patients demonstrated high complete response rates. Further, toxicities appeared manageable and occurred at rates lower than those reported for other CD19–directed CAR T-cell products.

“Though our follow-up is still relatively brief, many of these remissions are proving durable and will hopefully prove curative,” Abramson said.

Next, Abramson and colleagues plan to expand the study into a pivotal population in hopes of FDA approval.

“We’re very optimistic that moving forward, we’ll see very exciting results in an ongoing way that hopefully lead this drug to being available for patients worldwide,” he added.

Video at: https://www.healio.com/hematology-oncology/lymphoma/news/online/%7B011c8992-9847-4131-8fb5-ed961149343a%7D/video-cd19directed-car-t-cells-shows-promise-in-advanced-lymphomas

wmay13241