A list of studies: recent advances in CAR-T cell therapy (part four)

Posted by beauty33 on June 27th, 2019

5.Mol Ther Oncolytics: Coarse corn particles cause negative effect on eggshell quality of semi-heavy laying hens

Doi:10.1016/j.omto.2019.03.002

Recently, scientists from Japan and the United States developed a new and efficient CAR-T cell through joint research, published in the Molecular Therapy Oncolytics. The novel CAR-T cells carry herpes simplex virus into the mediation and co-stimulate signal domains and exhibit higher potential. Chimeric antigen receptor (CAR) is a hybrid molecule composed of an antigen binding protein and a signal transduction domain. CAR (CAR-T cells) expressed by artificial T cells is expected to be a kind of useful tool to treat a variety of diseases, including cancer. Adding a co-stimulatory signal domain (CSSD) to the CAR is critical for regulating the activity of CAR-T cells. However, the specific interaction between different types of CSSDs, effector functions, and CAR-T cell characteristics is not known.

To elucidate the interactions, the researchers analyzed the function of effectors, the differentiation of memory T cell subsets, depletion, and the energy metabolism mechanisms of CAR-T cells carrying different CSSDs, compared to CSSD-derived CSSD or in the case of 4-1BB-derived CSSD (which is used for CAR-T cell development), CAR-T cells carrying the herpes simplex virus entry mediated (HVEM)-derived CSSD can exhibit enhanced effector function, and it is effective and balanced to differentiate into central and effector memory cell subsets, and is also associated with increased levels of cellular energy metabolism and decreased levels of depletion.

The results of this study indicate that CSSD in CAR is a key determinant of the function and characteristics of CAR-T cell effectors. CSSD is very important for later scientists to design high-potential CAR-T cells. The new CAR-T cells developed by the researchers have high-efficiency HVEM-derived CSSD, which may help develop more potent CAR-T cells.

6.Hum Gene Ther: Preclinical Evaluation of Chimeric Antigen Receptor–Modified T Cells Specific to Epithelial Cell Adhesion Molecule for Treating Colorectal Cancer

Doi:10.1089/hum.2018.229

Researchers have found that cancer immunotherapy targeting the tumor biomarker epithelial cell adhesion molecule (EpCAM) is safe and non-toxic to mice, and can significantly delay tumor formation and growth. EpCAM is overexpressed in many types of tumors, circulating tumor cells, and cancer stem cells, so these findings have broad implications. The relevant research results were recently published in the special issue of Human Gene Therapy.

Dr. Adi Barzel, Ph.D., of Tel Aviv University and President of the Israel Society for Gene and Cell Therapy, is a guest editor of this special issue. This article is entitled "Preclinical Evaluation of Chimeric Antigen Receptor-Modified T Cells Specific to EpCAM for Treating Colorectal Cancer". Co-authors include Wei Wang and a group of researchers from Huaxi Hospital, Sichuan University Biotherapy Collaborative Innovation Center and the first affiliated hospital of Chongqing Medical University.

The researchers produced a third-generation of chi- meric antigen receptor-modified T (CAR-T) cell. They specifically target EpCAM in cells using a lentiviral vector.

"CAR-T therapy represents a breakthrough in the treatment of patients with B-cell leukemia and lymphoma, but unfortunately it progresses slowly in the treatment of solid tumors," said Terence R. Flotte, MD, editor-in-chief of the journal." This key study for patients with colorectal cancer suggests that targeted cancer immunotherapy may indeed play a role in this very common malignancy."

7.Adv Mat: Photothermal Therapy Promotes Tumor Infiltration and Antitumor Activity of CAR T Cells

Doi:10.1002/adma.201900192

A preclinical study led by scientists at the University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Institute has shown that heating solid tumors during CAR T cell therapy can increase the success rate of treatment. The researchers found that combining photothermal ablation heating with CAR T cell perfusion inhibited mouse melanoma growth for up to 20 days. Of the mice receiving the combination therapy, 33% of the mice still had no tumor after 20 days.

Genetically engineered T cells with chimeric antigen receptors (CAR) have been successfully used to treat many lymphoma and leukemia patients. However, CAR T cell therapy is not very effective in treating solid tumors because solid tumors have a protective microenvironment that makes it harder for CAR T cells to enter the tumor and maintain T cell activity. UCLA scientists decided to test whether the combination of CAR T therapy and photothermal therapy can overcome this obstacle. Photothermal therapy is a minimally invasive technique that uses the energy of laser energy to kill cancer cells; it has been used to treat a variety of cancers and other diseases.

The researchers tested whether mild hyperthermia at about 40 degrees Celsius could help CAR T cells attack tumors more effectively. The UCLA-led research team tested the technique in mice injected with human melanoma. The researchers injected the photothermal agent into the tumor and then heated it with a laser. Then, CAR T cells were injected intravenously. Using a laser to increase the tumor temperature to about 40 degrees Celsius contributes to the expansion of tumor-associated blood vessels and promotes T cell growth.

This technology can ultimately improve the prognosis of patients with solid tumors that are difficult to treat by enhancing the ability of CAR T cell therapy. Researchers will continue to test this strategy on animals to optimize heating time and temperature before deciding whether to test in the human body. Professor Gu Yu, a professor of bioengineering at the UCLA Samueli School of Engineering, a member of the Jonsson Cancer Center, and a member of the UCLA Nanosystems Institute, is a co-author of the study. Another author of the paper is Dr. Gianpietro Dotti of the University of North Carolina at Chapel Hill. The first author of the paper is Dr. Chen Qian, a postdoctoral researcher. The study was published in Advanced Materials.

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