Handcuffing the culprit cancer: Immunotherapy for cold tumors with trispecific antibody

February 18, 2021

Several treatments for cancer have been devised by science, but unfortunately none of them are completely efficient or foolproof. Novel treatments with minimum side effects are one of the main aims of the ongoing cancer research. All research so far points to several therapy modes, of which immunotherapy, which prepares the body's own immune system to fight cancer, is a promising option. Bispecific antibodies (BsAbs) are synthetically made proteins that emerged as a promising second-generation immunotherapy. They engage with immune cells and enable them to target cancer in a specific manner.

Conventional use of T cells for this therapy has caused adverse effects in some cases. Moreover, they are ineffective against cold tumors, which are invisible to T cells of the immune system. This led to a search for other immune cells that could effectively target cold tumors with minimum adverse effects. Natural killer (NK) cells have therefore gained attention as prospective immunotherapy agents.

Now, a research team from China has designed a trispecific antibody that targets cancer cells and NK cells using anti-CD16, -IL15, and -CD19 domains. They call this molecule "161519 TriKE." As Dr. Zhigang Tian, one of the members of this research team and co-corresponding author of this study, explains, "Our intention was to attract CD19-positive tumor cells (such as the cells in Burkitt's lymphoma) to CD16-positive NK cells. IL15 can be used to maintain continuous division, development, and survival of NK cells, increasing their efficiency. Simply put, this protein acts like a handcuff, bringing cancer cells to killer immune cells. Additionally, these handcuffs have a trigger that keeps the killer cells active to destroy the cancer cells more efficiently."

In their study published in Cancer Biology & Medicine, the scientists used 161519 TriKE to target CD19-positive cancer cells in cell culture and measured the expression of markers that signify a successful immune response. They observed that several such markers increased in cells treated with 161519 TriKE. To test its preclinical efficiency, researchers developed "immune-reconstituted xenograft" mouse models, which are genetically engineered mice that constitute human peripheral blood mononuclear cells (PBMCs) and human tumors and tested to see if 161519 TriKE is able to initiate an immune response. 161519 TriKE was found to improve the interaction between NK cells and CD19-positive tumor cells. The team also found that 161519 TriKE is able to initiate a strong cytotoxic action of NK cells against tumor cells in cell culture. These results were same in live animals as well. Not only could 161519 TriKE successfully reduce tumor growth, it could also increase the overall survival of tumor-bearing mice.

So, what does this mean for cancer medicine? Prof. Haoyu Sun, co-corresponding author, explains the implications of their findings, "This study effectively provides a new method to develop immunotherapies against cancer. 161519 TriKE has the ability to transform research into application and shows potential for drug development. It can also be used in combination with other NK cell-based therapies."

The fundamental knowledge about the mechanism of action of this new molecule, 161519 TriKE, has the potential to revolutionize the current immunotherapy technology and can be redesigned to target other types of cancers.

Authors: Ying Cheng (1,2), Xiaodong Zheng (1,2), Xuefu Wang (1,2), Yongyan Chen (1,2), Haiming Wei (1,2), Rui Sun (1,2), Zhigang Tian (1,2,3), Haoyu Sun (1,2)

Title of original paper: Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers

Journal:Cancer Biology & Medicine

DOI: 10.20892/j.issn.2095-3941.2020.0399


(1) Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China

(2) Institute of Immunology, University of Science and Technology of China, Hefei 230027, China

(3) Research Unit of NK Cell Study, Chinese Academy of Medical Sciences, Beijing 100864, China

About Dr. Zhigang Tian

Dr. Zhigang Tian is a professor at University of Science and Technology of China (USTC) in Hefei, China. He also serves as a Director of Institute of Immunology, Director of The CAS Key Lab of Innate Immunity and Chronic Diseases, and President of Medical Center at USTC, and is the former dean of School of Life Sciences. His research focuses on natural killer cells and immunotherapy associated with these cells, and he has published more than 300 papers in esteemed peer-reviewed journals.

About Dr. Haoyu Sun

Dr. Haoyu Sun is an associate professor at the University of Science and Technology of China (USTC) in Hefei, China. Her research focuses on natural killer cells and anti-tumor immunotherapies, and she has over 17 publications to her name.

Cactus Communications

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
Brightsurf.com 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 Amazon.com.