Featured Research

from universities, journals, and other organizations

Vaccine 'reprograms' pancreatic cancers to respond to immunotherapy

Date:
June 18, 2014
Source:
Johns Hopkins Medicine
Summary:
A vaccine that triggered the growth of immune cell nodules within pancreatic tumors, essentially reprogramming these intractable cancers and potentially making them vulnerable to immune-based therapies, has developed and tested by researchers. The reprogramming is designed to make the tumors more vulnerable to other immune-modulating drugs that have been useful in fighting other cancers, researchers explain.

Researchers at the Johns Hopkins Kimmel Cancer Center have developed and tested a vaccine that triggered the growth of immune cell nodules within pancreatic tumors, essentially reprogramming these intractable cancers and potentially making them vulnerable to immune-based therapies.

In their study described in the June 18 issue of Cancer Immunology Research, the Johns Hopkins team tested the vaccine in 39 people with pancreatic ductal adenocarcinomas (PDAC), the most common form of pancreatic cancer. The disease becomes resistant to standard chemotherapies and is particularly lethal, with fewer than 5 percent of patients surviving five years after their diagnosis.

PDACs do not typically trigger an immune response against the cancer cells that comprise, but with the help of a vaccine developed by Johns Hopkins researcher Elizabeth Jaffee, M.D., the scientists were able to "reprogram" tumors to include cancer-fighting immune system T cells.

The vaccine, known as GVAX, consists of irradiated tumor cells that have been modified to recruit immune cells to a patient's tumor. The researchers tested GVAX in combination with an immune modulator drug called cyclophosphamide, which targets a type of immune cell, called Tregs, that typically suppresses the immune response of certain T cells that destroy cancer.

The reprogramming is designed to make the tumors more vulnerable to other immune-modulating drugs that have been useful in fighting other cancers, said Jaffee, The Dana and Albert "Cubby" Broccoli Professor of Oncology at the Johns Hopkins University School of Medicine.

Jaffee and colleague, Lei Zheng, M.D., say the vaccine could potentially convert many types of tumors to a state where immunotherapies can have a much larger impact.

For example, Jaffee says, in certain melanomas, "we've tested immunotherapies that target T cells and have found a 10-30 percent response in cancers that naturally have the ability to trigger immune system responses, but there are few options for the other 70 percent of patients who barely or never respond to immunotherapies."

The researchers found that the vaccine created structures called tertiary lymphoid aggregates within the patients' tumor, structures that help regulate immune cell activation and movement. The aggregates, which appeared in 33 of the 39 patients treated with the vaccine, had surprisingly well-organized structures that do not typically appear in these types of tumors naturally, said Zheng, an assistant professor of oncology and surgery at the Johns Hopkins University School of Medicine. "This suggests that there has been significant reprogramming of lymphocyte structures within the tumor."

The aggregates could "really shift the immunologic balance within a tumor, setting up an environment to activate good T cells to fight the cancer, by tamping down Tregs," Jaffee said, "and such T cells would be educated to recognize the cancer proteins in that specific tumor environment."

The vaccine and the resulting lymphoid aggregates boosted the activity of several molecular mechanisms that, like Tregs, inhibit cancer-fighting immune cells. That may sound like a bad thing, but it actually provides many new potential targets within the tumor for immune-modulating drugs, Zheng explained.

The researchers' next study in PDAC patients will test a combination of GVAX and an antibody to PD-1, one of the immune-suppressing molecules that became more active after vaccination. "We think combinations of immune therapies will have the biggest impact," he says.


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Eric R. Lutz, Annie A. Wu, Elaine Bigelow, Rajni Sharma, Guanglan Mo, Kevin Soares, Sara Solt, Alvin Dorman, Anthony Wamwea, Allison Yager, Daniel Laheru, Christopher L. Wolfgang, Jiang Wang, Ralph H. Hruban, Robert A. Anders, Elizabeth M. Jaffee, and Lei Zheng. Immunotherapy Converts Nonimmunogenic Pancreatic Tumors into Immunogenic Foci of Immune Regulation. Cancer Immunology Research, June 2014 DOI: 10.1158/2326-6066.CIR-14-0027

Cite This Page:

Johns Hopkins Medicine. "Vaccine 'reprograms' pancreatic cancers to respond to immunotherapy." ScienceDaily. ScienceDaily, 18 June 2014. <www.sciencedaily.com/releases/2014/06/140618071559.htm>.
Johns Hopkins Medicine. (2014, June 18). Vaccine 'reprograms' pancreatic cancers to respond to immunotherapy. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2014/06/140618071559.htm
Johns Hopkins Medicine. "Vaccine 'reprograms' pancreatic cancers to respond to immunotherapy." ScienceDaily. www.sciencedaily.com/releases/2014/06/140618071559.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins