Nav: Home

New technique helps create more personalized therapies for people with advanced cancers

July 22, 2019

UCLA RESEARCH ALERT

FINDINGS

Being able to identify targets for adoptive cell therapies is one of the first steps in developing personalized treatments for people with hard-to-treat cancers. However, predicting whether a patient will have an immune response to a particular abnormal protein caused by mutations that serves as a new antigen (neoantigen), can be challenging. Using an ultra-sensitive and high-throughput isolation technology (termed imPACT Isolation Technology®) designed to isolate neoepitope specific T-cells, UCLA researchers were able to characterize and identify the neoantigens driving the antitumor responses in a patient treated with anti-PD-1 blockade and isolate the T cell receptors responsible for such effect.

BACKGROUND

Using immune checkpoint inhibitors to treat people with metastatic melanoma has helped transform the way people with the most deadly skin cancer are treated. Despite its success, there are still many people who do not benefit from the treatment. Up until now, adoptive cell therapy, which involves extracting and harvesting T cells from a patient and engineering them in the laboratory, have targeted shared antigens. That restricts many of the people that can potentially be treated with the therapy because not every cancer has the same antigen that needs to be targeted. Researchers are working to improve methods to identify new targets for these therapies in hopes to develop more effective and personalized therapies.

METHOD

Researchers analyzed T cell responses in two patients with advanced melanoma, one who responded to anti-PD1 therapy and one who did not respond to the therapy. Using samples collected before and during treatment, the team isolated the T cells specifically recognizing the mutations on the tumor by using the imPACT Isolation Technology® developed by PACT Pharma. The technology allows researchers to identify the T cells, and their T cell receptors, that have the ability to detect mutations. After identifying the T cell receptors, they were re-introduced in T cells from peripheral blood using a non-viral genome engineering method to generate new neoantigen-specific T cells that were used to kill melanoma cells from the same patient.

"In the setting of patients treated with anti-PD-1, we identified for the first time, in a high-throughput manner, which neoantigen mutations in the tumor are being targeted by T cells. More importantly, we were able to identify their T cell receptors and demonstrate that they can actually specifically kill the tumor cells," said lead author Cristina Puig-Saus, PhD, associate project scientist in hematology/oncology at the David Geffen School of Medicine at UCLA. "We hope that a better understanding of the T cell responses that occur after immune checkpoint blockade will guide the design of personalized adoptive T cell therapies."

IMPACT

Uncovering new ways to identify targets for immunotherapies significantly increases the number of patients who will benefit from immunotherapy. The imPACT Isolation Technology® allows researchers to identify the mutation-specific T cells and understand which mutations are inducing responses against tumors.

AUTHORS

Lead author is Cristina Puig-Saus, PhD, an associate project scientist in hematology/oncology at the David Geffen School of Medicine at UCLA. Senior author is Antoni Ribas, MD, PhD., director of the tumor immunology program at the UCLA Jonsson Comprehensive Cancer Center and professor of medicine in the David Geffen School of Medicine at UCLA. Thirty-three additional authors are listed in the abstract.

JOURNAL

The research was featured at the American Associate of Cancer Research special conference on immune cell therapies for cancer.
-end-
FUNDING

The research was supported by the Parker Institute for Cancer Immunotherapy.

DISCLOSURES

Ribas is on the board of directors, the scientific advisory board and holds stock in PACT Pharma, who developed the imPACT Isolation Technology®.

The UCLA Jonsson Comprehensive Cancer Center has approximately 500 researchers and clinicians engaged in cancer research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the UCLA Jonsson Comprehensive Cancer Center is dedicated to promoting research and translating basic science into leading-edge clinical studies.

Link to conference/abstract: https://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=178

University of California - Los Angeles Health Sciences

Related Cancer Articles:

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.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
More Cancer News and Cancer Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.