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Posts Tagged ‘B-cells’


Cancer Drugs Shed Light on Rheumatism

Reporter: Irina Robu, PhD

The human body is often described as being ‘at war’. By this, it is meant that the body is constantly under attack from things that are trying to do it harm. These include toxins, bacteria, fungi, parasites and viruses. The human immune system is one of the most effective defense mechanisms known to nature and can sometimes can be overwhelmed by disease. Yet, on occasions our immune systems turn on our own tissue and attack it which can trigger conditions such as type I diabetes, rheumatoid arthritis and lupus.
In the case of rheumatoid arthritis, immune cells start to attack tissues in the joins which causes them to become painful, stiff and swollen. It is known that one third of those who develop rheumatoid arthritis, feel the horrible effects of the disease within two years of its onset.
Immunologist Adrian Hayday, which is a researcher at Francis Crick Institute of London says that the current treatment for rheumatoid arthritis require patients to take the drugs for the rest of their lives. But, researchers such as Hayday found an unexpected ally in the battle against autoimmune disease, cancer.
However, there is a positive consequence to the discovery that cancer immunotherapies have the effect of triggering autoimmune diseases and for the first-time rheumatoid arthritis can be detected at the earliest stages. At present, people are not diagnosed with the condition until symptoms have already made their lives so unpleasant, they have gone to see their doctors. As a result, research backed by Cancer Research UK and Arthritis Research UK, has been launched with the aim of uncovering the roots of autoimmune disease from research on cancer patients.
The scientists mentioned stress that their work is only now start and warn that it will still take several years of research to get substantial results. Nevertheless, uncovering the first stages of an autoimmune disease emerging in a person’s body should give researchers a vital lead in ultimately developing treatments that will prevent or halt a range of conditions that currently cause a great deal of misery and require constant medication.
Our immune defenses consist of a range of cells and proteins that notice invading micro-organisms and attack them. The first line of defense, yet, consists of simple physical barriers similar to skin, which blocks invaders from entering your body. When this defense is penetrated, they are attacked by a number of agents. The key cells, leukocytes seek out and destroy disease-causing organisms. Neutrophils rush to the site of an infection and attack invading bacteria. Helper T-cells give instructions to other cells while killer T-cells punch holes in infected cells so that their contents ooze out. After these macrophages clean up the mess left behind.
Another significant agent is the B-cell, which produces antibodies that lock on to sites on the surface of bacteria or viruses and immobilize them until macrophages consume them. These cells can live a long time and can answer quickly following a second exposure to the same infections. In conclusion, suppressor T-cells act when an infection has been distributed with and the immune system needs to be reassured, the killer cells may keep on attacking, as they do in autoimmune diseases. By slowing down the immune system, regulatory T-cells prevent damage to “good” cells.

Source

https://www.theguardian.com/science/2018/mar/03/immunotherapy-cancer-patients-rheumatoid-arthritis-robin-mckie

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Controlling CAR-T cells

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

New discovery – Remote control of CAR-T cells

T cells, Cancer immune therapy, autoimmune

CAR-T cells have been emerging as an effective approach to treat cancer and autoimmune diseases. A problem with CAR-T cells is that once they are infused, they are on their own exerting autonomous activities, which can lead to severe side effects due to the extensive lysis of tumor cells. Researchers have been seeking ways to control CAR-T cells after they are infused to balance the desired therapeutic effect and the side effect. Recently, a group of researchers at UCSF found a way to control CAR-T cells after they are put into patients, through a rapamycine analogue gated chimeric receptor.

CAR-T cell system has two components: one is the recognition domain that binds to CD19 to target B cells; the other is the functional domain to activate cellular pathways to killing the targeted cells. Those two domains are typically preassembled. What this group of researchers did is to separate those two domains and make them come together only in the presence of the activating molecule, a rapamycine analogue. They showed that in the absence of the activating molecule, CAR-T cells still bound to CD19. But, they didn’t kill the targeted cells unless the activating molecule was present. In addition, by adjusting the dose of the activating molecule, the strength of CAR-T cells activities can be titrated as well.

Chia-Yung Wu, etc. (October 2015) Remote control of therapeutic T cells through a small molecule–gated chimeric receptor.Science

 

Remote control of therapeutic T cells through a small molecule–gated chimeric receptor

 

 

https://pharmaceuticalintelligence.com/2016/02/06/reengineering-therapeutics/

Reengineering Therapeutics

Larry H. Bernstein, MD, FCAP, Curator

LPBI

The synNotch solution: UCSF scientists engineer a next-gen T-cell immunotherapy

Sunday, January 31, 2016 | By John Carroll

CAR-T has been all the rage in cancer R&D for several years now as a slate of biotech upstarts pursue highly promising work reengineering T cells into attack weapons by adding a chimeric antigen receptor that can zero in on particular cancer cells. The approach has been highly effective in acute lymphoblastic leukemia, triggering an attack on B cells by homing in on the CD19 antigen, a breakthrough that has inspired a race to the regulatory finish line with the first CAR-Ts.

 

https://pharmaceuticalintelligence.com/2016/02/11/regulatory-dna-engineered/

Regulatory DNA engineered

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

New Type of CRISPR Screen Probes the Regulatory Genome

Aaron Krol    http://www.bio-itworld.com/2016/2/8/new-type-crispr-screen-probes-regulatory-genome.html

February 8, 2016 | When a geneticist stares down the 3 billion DNA base pairs of the human genome, searching for a clue to what’s gone awry in a single patient, it helps to narrow the field. One of the most popular places to look is the exome, the tiny fraction of our DNA―less than 2%―that actually codes for proteins. For patients with rare genetic diseases, which might be fully explained by one key mutation, many studies sequence the whole exome and leave all the noncoding DNA out. Similarly, personalized cancer tests, which can help bring to light unexpected treatment options, often sequence the tumor exome, or a smaller panel of protein-coding genes.

 

sjwilliamspa commented on Controlling CAR-T cells

Controlling CAR-T cells Larry H. Bernstein, MD, FCAP, Curator LPBI New discovery – Remote control of CAR-T cells CAR-T …

Interesting method to use a chimeric heterodimer receptor to control CD19 activity however it would be ineresting to see if cancer replapses occur more frequently. Originally it was thought the CART would act, after initial treatment, eventually to patrol the body for any recurring tumor cells. Using rapamycin would be interesting although there had been some immunotoxic concerns with chronic use (although long term use of rapamycin and other mtor inhibitors seemed to prolong lifespan in immunodeficient animals)

Temsirolimus, an Inhibitor of Mammalian Target of Rapamycin athttp://clincancerres.aacrjournals.org/content/14/5/1286.short

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Thymus vs Bone Marrow, Two Cell Types in Human Immunology: B- and T-cell differences

Reporter: Larry H. Bernstein, MD, FCAP

Differences Between B-Cells and T-Cells

http://www.microbiologyinfo.com/differences-between-b-cells-and-t-cells/

Aryal Sagar

Although mature lymphocytes all look pretty much alike, they are extraordinarily diverse in their functions. The most abundant lymphocytes are:

B lymphocytes (often simply called B cells) and
T lymphocytes (likewise called T cells)

Differences between B-Cells and T-Cells

http://www.microbiologyinfo.com/wp-content/uploads/2015/11/Differences-between-B-Cells-and-T-Cells.jpg

S.N.

Properties

B-Cells

T-Cells

1 Name B lymphocytes T lymphocytes
2 Origin Bone Marrow Thymus
3 Position Outside Lymph Node Interior of Lymph Node
4 Membranereceptor BCR (= immunoglobulin) for antigen TCR for antigen
5 Connections B-cells can connect to antigens right on the surface of the invading virus or bacteria. T-cells can only connect to virus antigens on the outside of infected cells.
6 Tissue Distribution Germinal centres of lymph nodes, spleen, gut, respiratory tract; also subcapsular and medullary cords of lymph nodes Parafollicular areas of cortex innodes, periarteriolar in spleen
7 Life Span Life span is short Life span is long
8 Surface Antibodies Surface Antibodies present Absence of surface antibodies
9 Secretion They secrete antibodies They secrete Lymphokines
10 Function В-cells form humoral or antibody-mediated immune system (AMI). T-cells form cell-mediated immune system (CMI).
11 Blood 20% of lymphocytes 80% of lymphocytes; CD4 > CD8
12 Formation They form plasma cells and memory cells. They form killer, helper and suppressor cells.
13 Movement to Infection Site Plasma cells do not move to the site of infection. Lymphoblasts move to the site of infection.
14 Function Plasma cells do not react against transplants and cancer cells. Killer cells react against transplants and cancer cells.
15 Function Plasma cells have no inhibitory effect on immune system. Suppressor cells inhibit immune system.
16 Function They defend against viruses and bacteria that enter the blood and lymph. They defend against pathogens including protists and fungi that enter the cells.
Differences Between B-Cells and T-Cells

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