Immune cells fighting blood cancer visualized for the first time

April 08, 2019

When cancer escapes the immune system, our defenses are rendered powerless and are unable to fight against the disease. Chimeric antigen receptor T cells (CAR T cells) represent a promising immunotherapy strategy, developed with the aim of tackling tumors head-on. But the occurrence of relapse in some patients remains a challenge. Scientists at the Institut Pasteur have identified the precise function of CAR T cells in a bid to optimize future therapies.

One of the strategies used to combat cancer is based on modification of the patient's T lymphocytes (also known as natural killer cells) to make them recognize the target molecule CD19 expressed by the tumor, so that they can eliminate it. Clinical trials have proved to be remarkably effective, leading to the use of this technique in adults and children to treat blood cancer (B-cell lymphomas and leukemia). But some patients suffer relapses. To improve therapies in future, scientists from the Institut Pasteur set out to elucidate the precise workings of CAR T cells.

The inner workings of immunity

Marine Cazaux and Capucine Grandjean, together with their colleagues in the Dynamics of Immune Responses Unit (Institut Pasteur/Inserm) led by Philippe Bousso, in collaboration with scientists from the Universities of Manchester (UK) and Leiden (NL), visualized CAR T cells battling a tumor for the very first time. Using a novel high-resolution in vivo imaging technique, they observed the bone marrow of mice with lymphoma. This enabled them to investigate the overall behavior of CAR T cells and to visualize in real time the interactions between CAR T cells and the tumor, as well as tumor death (imaged using an ingenious technique that changes the color of cancer cells after they die). Even if some CAR T cells are more active than others, they demonstrated that in general, a CAR T cell is capable of directly killing a tumor cell within approximately 25 minutes of recognizing its target.

The key role of CAR T cells in the fight against cancer

"Mathematical simulations based on our experimental data confirm that the efficacy of CAR T cells is primarily based on their ability to engage and directly kill the cancer cell rather than recruiting other immune cells to the tumor site," explains Philippe Bousso. These simulations also demonstrated that the number of CAR T cells that are able to infiltrate the bone marrow plays a major role in treatment efficacy.

A significant obstacle for this infiltration is that CAR T cells in the bloodstream encounter tumor cells and B lymphocytes that also express the target CD19. The team observed that CAR T cells form cellular aggregates which become trapped in the pulmonary circulation, preventing their migration to the tumor site. Reducing the number of cells expressing CD19 before the injection of CAR T cells significantly improved the overall survival of the mice.

The research also revealed differences in activity level depending on the anatomical site. CAR T activity was stronger in the bone marrow than at other tumor sites (e.g. the lymph nodes), enabling it to exert selective pressure on tumor cells and resulting in the emergence of cells no longer expressing CD19.

"By identifying the strengths and weaknesses of CAR T cells in action, this research opens up new avenues for exploiting and optimizing the activity of CAR T cells in patients," concludes Philippe Bousso.
To watch the video of the visualization of CART cells in action:

Institut Pasteur

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to