Science Bites seeks to compile the latest scientific research updates in bite-sized forms.

1. Scientists break ‘legs’ of cancer cells to stop metastasis


When cancer metastasises in the body, treatment options quickly become limited. Now, scientists may have discovered the key to stopping this process – by cutting off the protrusions on cancer cells that help it spread. Mostafa El-Sayed, Julius Brown Chair and Regents Professor of Chemistry and Biochemistry at Georgia Tech’s School in Atlanta, led the team of researchers.

The ‘legs’ of cancer cells – filopodia – are an extension of a set of "broad, sheet-like" fibers called lamellipodia. The latter can be found around the cellular edges. Basically, lamellipodia and filopodia aid healthy cells to move within the tissue but are overproduced in cancer cells.

With nanotechnology, scientists can shrink certain materials to a nanoscale to a point where the materials portray altered physical and chemical properties. El-Sayed and his team covered nanorods with a coating of molecules, called RGD peptides. This allowed for them to be specifically attached to the integrin protein when introduced locally. This process, in itself, delayed cancer cell migration and even avoided healthy cells.

Yan Tang, postdoctoral assistant in computational biology and co-author of the study explained, “The targeted nanorods tied up the integrin and blocked its functions, so it could not keep guiding the cytoskeleton to overproduce lamellipodia and filopodia.”

In the second stage of the experiment, the team heated the nanorods with a near-infrared light laser. Moustafa Ali, a study author, said, “The light was not absorbed by the cells, but the gold nanorods absorbed it, and as a result, they heated up and partially melted cancer cells they are connected with, mangling lamellipodia and filopodia.”

Authors say the laser can reach about 4 to 5 centimetres deep inside the tissue and deeper tumours can be treated with deeper nanorods injections.

A CAR-T cell (reddish) attacking a leukemia cell (green). These CAR-T lymphocytes are used for immunotherapy against cancer. Photo credit: Eye of Science/Science Source/NPR
A CAR-T cell (reddish) attacking a leukemia cell (green). These CAR-T lymphocytes are used for immunotherapy against cancer. Photo credit: Eye of Science/Science Source/NPR

2. FDA advisory committee unanimously recommend CAR-T cell immunotherapy for ALL


The CAR-T cell immunotherapy, which uses genetically engineered cells from the patient's own immune system to treat their cancer, got the thumbs up from the Food and Drug Administration (FDA) advisory committee. They unanimously recommended that the FDA approve the “living drug” treatment for acute lymphoblastic leukaemia. The FDA usually agrees with the committee and, if approved, it would be the first time the agency approves a “gene therapy product”.

Over the years, researchers have attempted to utilise immune system-stimulating drugs to fight cancer with little success. This CAR-T cell immunotherapy works by removing the patient’s T-cells and modifying them to seek out and attack only cancerous cells. Clinicians, successively, infuse millions of these genetically modified T cells back into the patient's body to eradicate the cancer cells and avoid targeting healthy tissue.

Dr. David Lebwohl, who heads the CAR-T Franchise Global Program at Novartis said, “It's truly a paradigm shift. It represents a new hope for patients. The product has been shown to result in a high rate of response.”

CTL019 or tisagenlecleucel is the drug recommended by the advisory panel. It aims to treat children and young adults between 3 to 25 years old who have relapsed after undergoing standard treatment for B cell acute lymphoblastic leukaemia. In the main study, 88 patients who could not be treated with the standard regime, received CAR-T therapy. 83% of patients went into remission with Tisagenlecleucel.

3. Key molecules found to aid cancer cells evade immune system


Investigators, led by Niroshana Anandasabapathy at Brigham and Women's Hospital, have discovered an important way some cancers evade the immune system. They studied 30 human cancers of the peripheral tissue, including melanoma skin cancer.

Anandasabapathy explained, “Our study reveals a new immunotherapy target and provides an evolutionary basis for why the immune system may fail to detect cancers arising in tissues.”

“The genetic programme we report on helps the immune system balance itself. Parts of this programme prevent the immune system from destroying healthy organs or tissues, but might also leave a blind spot for detecting and fighting cancer,” she added.

Immune mononuclear phagocytes were studied. Even though they have different functions, all these phagocytes found in the skin and peripheral tissue have similar genetic programming. The research team noted that interferon gamma (IFN-gamma) prompts the programme via an “instructive cue” in healthy cells but IFN-gamma and tissue immune signatures are significantly higher in skin cancer.

This type of programme might contain important molecules to decrease inflammation but also leave a blind spot to cancer detection. Investigators studied the suppression of cytokine signalling 2 (SOCS2) – when switched off, the immune system could detect and reject cancer in melanoma and thymoma models.

“Our research suggests that these cancers are co-opting tissue-specific immune development to escape detection, but we see that turning off SOCS2 unmasks them.”

“This sheds new light on our understanding of how the immune system is programmed to see cancers and also points the way toward new therapeutic targets for treating cancers that have these signatures,” said Anandasabapathy. MIMS

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Sources:
http://www.medicalnewstoday.com/articles/318149.php
http://www.npr.org/sections/health-shots/2017/07/12/536812206/living-drug-that-fights-cancer-by-harnessing-the-immune-system-clears-key-hurdle
https://medicalxpress.com/news/2017-06-insights-immune-cancer.html