UCLA scientists create army of tumor-fighting immune cells and watch as they attack cancer

July 12, 2010

Researchers at UCLA's Jonsson Comprehensive Cancer Center created a large, well armed battalion of tumor-seeking immune system cells and watched, in real time using Positron Emission Tomography (PET), as the special forces traveled throughout the body to locate and attack dangerous melanomas.

The gene therapy work, done with melanomas grown in mice, employed a crippled HIV-like virus to serve as a vehicle to arm the lymphocytes with T cell receptors, which caused the lymphocytes to become specific killers of cancerous cells. A reporter gene, which glows "hot" during PET scanning, also was inserted into the cells so researchers could track the genetically engineered lymphocytes after they were injected into the blood stream, made their way to the lungs and lymph nodes and then specifically homed in on the tumors wherever they were located within the body.

"We're trying to genetically engineer the immune system to become a cancer killer and then image how the immune system operates at the same time," said Dr. Antoni Ribas, an associate professor of hematology/oncology, a researcher at UCLA's Jonsson Comprehensive Cancer Center and the senior author of the study. "We knew this approach of arming the lymphocytes with T cell receptors showed significant anti-tumor activity based on studies in humans. Now, by tracking the immune system's reaction to cancer and imaging it in real time, we can project how the same process that succeeded in mice might behave in people."

The study is published July 12, 2010 in the early online edition of the journal Proceedings of the National Academy of Sciences.

"The novelty of our work is that we were able to pack together the cancer specific T cell receptor and the PET reporter genes in a single vector and use it in mice with an intact immune system that closely resembles what we would see in real patients," said Dr. Richard Koya, an assistant professor of surgical oncology at UCLA's David Geffen School of Medicine and first author of the study. "We were also gladly surprised to see the targeted tumors literally melt away and disappear, underscoring the power of the combined approach of immune and gene therapy to control cancer."

The immune system generally does not recognize cancer cells in the body as enemies. The insertion of the antigen-specific T cell receptors - engineered to seek out a tumor antigen on the surface of the melanoma cells - in effect uncloaks the malignant cells, revealing them as deadly invaders that must be sought out and killed.

By imaging the genetically engineered T cells as they seek out and attack the cancer, the scientists can closely examine the processes of the immune system as it fights malignancies , which could then result in better monitoring response to therapy in melanoma patients.

In this study, the cells were injected into the bloodstreams of the mice and they had found and begun to fight the melanoma within two to three days. The mice were imaged periodically for 10 days to ensure the lymphocytes were indeed killing the cancer. The process to find and kill the malignant cells could take longer in people, Ribas said.

If a patient's tumor did not respond well to the administration of the genetically engineered T cells, scientists could determine by PET scanning whether the cells had not successfully made it to the tumor site or, if they did arrive, whether or not they functioned as expected. Monitoring the immune response also could provide clues on ways to better engineer the lymphocytes to more effectively enter and attack the tumors.

In this study, about one million genetically engineered lymphocytes were created and injected into a mouse. In humans, the number of tumor-seeking cells needed to fight the cancer is about one billion, Ribas said.

Ribas and his team are working now on creating a vector, or vehicle, to insert the T cell receptors and reporter gene into the lymphocytes in a way that is safe to use in humans. If all goes well, human studies of the process could begin in about a year, Ribas said.
-end-
This study was funded by an In vivo Cellular and Molecular Imaging Center grant from the National Institutes of Health and by the V Foundation - Gil Nickel Family Fellowship in Melanoma Research at UCLA's Jonsson Comprehensive Cancer Center.

UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2009, the Jonsson Cancer Center was named among the top 12 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 consecutive years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.

University of California - Los Angeles Health Sciences

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.