• HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
  • CONTACT US
Friday, September 22, 2023
BIOENGINEER.ORG
No Result
View All Result
  • Login
  • HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
        • Lecturer
        • PhD Studentship
        • Postdoc
        • Research Assistant
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
  • CONTACT US
  • HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
        • Lecturer
        • PhD Studentship
        • Postdoc
        • Research Assistant
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
  • CONTACT US
No Result
View All Result
Bioengineer.org
No Result
View All Result
Home NEWS Science News Cancer

Study discovers triple immunotherapy combination as possible treatment for pancreatic cancer

Bioengineer by Bioengineer
December 30, 2022
in Cancer
Reading Time: 3 mins read
0
Share on FacebookShare on TwitterShare on LinkedinShare on RedditShare on Telegram

HOUSTON ― Researchers at The University of Texas MD Anderson Cancer Center have discovered a novel immunotherapy combination, targeting checkpoints in both T cells and myeloid suppressor cells, that successfully reprogrammed the tumor immune microenvironment (TIME) and significantly improved anti-tumor responses in preclinical models of pancreatic cancer.

Ronald DePinho, M.D.

Credit: The University of Texas MD Anderson Cancer Center

HOUSTON ― Researchers at The University of Texas MD Anderson Cancer Center have discovered a novel immunotherapy combination, targeting checkpoints in both T cells and myeloid suppressor cells, that successfully reprogrammed the tumor immune microenvironment (TIME) and significantly improved anti-tumor responses in preclinical models of pancreatic cancer.

In this study, published today in Nature Cancer, researchers used comprehensive immune profiling in mouse and human pancreatic cancers to systematically identify mechanisms of immunotherapy resistance and investigate potential therapeutic targets. They found that neutralizing several distinct immunosuppressive mechanisms of the TIME dramatically improved survival rates in laboratory models, pointing to a potential treatment option for this notoriously lethal and unresponsive cancer.  

“This triple combination therapy led to an unprecedented curative response in our models,” said corresponding author Ronald DePinho, M.D., professor of Cancer Biology. “The prevailing view has been that pancreatic cancer is impervious to immunotherapy, but this preclinical study shows that it can be vulnerable to the right combination therapy. Moreover, the presence of these targets in human pancreatic cancer specimens raises the exciting possibility that such therapeutic combinations could one day help our patients.”

Pancreatic cancer is one of the leading causes of cancer death in the United States, partially because 80% of cases are diagnosed at an advanced stage. Pancreatic cancer is also considered to be “non-immunogenic,” meaning it is unresponsive to commonly used anti-PD-1 and anti-CTLA-4 immune checkpoint inhibitors. This is due in part to the immunosuppressive conditions in the TIME, but the mechanisms behind this resistance are not fully understood.

The researchers used high-dimensional immune profiling and single-cell RNA sequencing to study how the TIME is affected by a variety of immunotherapies. They identified specific immune checkpoint proteins, 41BB and LAG, that were highly expressed in exhausted T cells.

In testing antibodies targeting these checkpoints, the researchers observed that models treated with a 41BB agonist and LAG3 antagonist in combination had slower tumor progression, higher levels of anti-tumor immunity indicators and significantly improved survival rates compared to treatment with either antibody alone or with other checkpoint inhibitors. Notably, these preclinical studies faithfully mirrored the human data in their lack of efficacy of anti-PD1 or anti-CTLA-4 therapy.

The researchers also confirmed these two therapeutic targets are present in human pancreatic cancer samples, with 81% and 93% of patients analyzed having T cells with 41BB and LAG3 expression, respectively. 

Because this dual-therapy combination did not completely eliminate established tumors, the investigators also examined efforts to reprogram the TIME to further sensitize tumors to immunotherapy. At baseline, the TIME contained an abundance of myeloid-derived suppressor cells (MDSCs) expressing CXCR2, a protein associated with recruiting immunosuppressive cells. Inhibiting CXCR2 alone decreased MDSC migration and blocked tumor growth, but it was not curative. This prompted the investigators to consider a combination targeting 41BB, LAG3 and CXCR2.

It was this triple combination that resulted in complete tumor regression and improved overall survival in 90% of preclinical models. In a more stringent lab model that develops multiple spontaneously arising tumors with higher treatment resistance, the combination achieved complete tumor regression in over 20% of cases.

“These are encouraging results, especially considering the lack of effective immunotherapy options in pancreatic cancer,” DePinho said. “By targeting multiple synergistic mechanisms that get in the way of the immune response, we can give T cells a fighting chance to attack these tumors. Of course, we still need to see how this combination translates into a safe and effective regimen in the clinic, and we invite other researchers to build upon these results. We are optimistic that pancreatic cancers, and hopefully other non-immunogenic cancers, can ultimately be rendered vulnerable to combination immunotherapy.”

The authors point out that these particular immunotherapy agents currently are undergoing clinical trials as monotherapies, suggesting potential opportunities to rapidly translate this triple combination into clinical studies.

This work was supported by the National Institutes of Health/National Cancer Institute (P01 CA117969, RO1CA240526, RO1CA236864, R01CA231349, R01CA220236, P50CA221707),  the Elsa U. Pardee Foundation, MD Anderson’s Advanced Scholar Program, the Eleanor Russo Fund for Pancreatic Research, Ralph A. Loveys Family Charitable Foundation, the Cultural & Charitable Club of Somerset Run, the New Jersey Health Foundation, the Sheikh Ahmed Bin Zayed Al Nahyan Center for Pancreatic Cancer Research, and MD Anderson’s Pancreatic Cancer Moon Shot®. A full list of collaborating authors and their disclosures can be found with the full paper here.

– 30 –



Journal

Nature Cancer

Share13Tweet8Share2ShareShareShare2

Related Posts

Immune Cells

Australian research leads to clinical trial for rare women’s cancers

September 22, 2023
Annika Wylie

Cancer Prevention and Research Institute of Texas awards $2 million grant to SMU

September 21, 2023

Rewiring tumor mitochondria enhances the immune system’s ability to recognize and fight cancer

September 21, 2023

Combination of cancer vaccine and T cell therapy benefits patients with advanced ovarian cancer

September 21, 2023

POPULAR NEWS

  • blank

    Microbe Computers

    58 shares
    Share 23 Tweet 15
  • University of South Florida scientist: Barnacles may help reveal location of lost Malaysia Airlines flight MH370

    46 shares
    Share 18 Tweet 12
  • Lithuanian invention at the forefront of solar technology breakthrough

    41 shares
    Share 16 Tweet 10
  • A pioneering study from Politecnico di Milano sheds light on one of the still poorly understood aspects of cancer

    34 shares
    Share 14 Tweet 9

About

We bring you the latest biotechnology news from best research centers and universities around the world. Check our website.

Follow us

Recent News

One-stop implementation from signal detection to processing

Australian research leads to clinical trial for rare women’s cancers

Ochsner offers tuition assistance to aspiring nurses and doctors

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

Join 57 other subscribers
  • Contact Us

Bioengineer.org © Copyright 2023 All Rights Reserved.

No Result
View All Result
  • Homepages
    • Home Page 1
    • Home Page 2
  • News
  • National
  • Business
  • Health
  • Lifestyle
  • Science

Bioengineer.org © Copyright 2023 All Rights Reserved.

Welcome Back!

Login to your account below

Forgotten Password?

Retrieve your password

Please enter your username or email address to reset your password.

Log In