Tuesday, June 15, 2021

 

What Changes to Your Diet and Exercise Routine Have Helped You Since Diagnosis?
From Ovarian Cancer Research Coalition: Those who have faced an ovarian or gynecologic cancer diagnosis have so much to offer to others going through a similar experience – be it support, tips or friendship. Inspired Advice is a blog series that tackles specific topics – from managing feelings of isolation to navigating a new diagnosis – and shares advice and reflections from our OCRA Inspire Online Community. They are, in many ways, the experts.*

*OCRA Note:Sharing ideas and experiences can be extremely helpful but, as always, we advise speaking with your physician before making any dietary changes or adding herbs, teas, vitamins or supplements to your routine.

Smart Cell Therapies for Solid Cancers Ready to Move Toward Clinical Trials



This article first appeared in UCSF and was written by Lindzi Wessel.

Immunotherapies that fight cancer have been a life-saving advancement for many patients, but the approach only works on a few types of malignancies, leaving few treatment options for most cancer patients with solid tumors.

Now, in two related papers published April 28, 2021, in Science Translational Medicine, researchers at UCSF have demonstrated how to engineer smart immune cells that are effective against solid tumors, opening the door to treating a variety of cancers that have long been untouchable with immunotherapies.

By “programming” basic computational abilities into immune cells that are designed to attack cancer, the researchers have overcome a number of major hurdles that have kept these strategies out of the clinic up to now. The two new papers show that the resulting “smart” therapies are more precise, flexible and thorough than previous approaches, and the researchers say that their approach may be ready for clinical trials in the near future.

In one paper, research teams led by Wendell Lim, PhD, chair and Byers Distinguished Professor of cellular and molecular pharmacology, and Hideho Okada, MD, PhD, the Kathleen M. Plant Distinguished Professor of neurological surgery, tested the system in glioblastoma, the most aggressive form of brain cancer that affects adults and children, and which physicians have yet to successfully treat with immunotherapies due to the complexity of the tumors. The team showed the new system, which uses a two-step process to hunt down cancer cells, could completely clear human patient-derived tumors from the brains of mice without the dangerous side effects or high risk of recurrence currently associated with immunotherapy treatment in solid tumors.

In the second paper, Kole Roybal, PhD, assistant professor of microbiology and immunology, and Bin Liu, PhD, professor of anesthesia at UCSF, led a study showing how components of this system can be switched out like the heads of an interchangeable screwdriver to target other difficult-to-treat cancers in other parts of the body. The team also identified a particularly important set of “screwdriver heads” that could make powerful tools against cancers of the ovaries, lungs and other organs, which together kill tens of thousands every year.

In addition, both papers address the issue of so-called “T-cell exhaustion,” a long-standing challenge in which traditional CAR-T cells — the re-programmed intruder-hunting immune cells behind some of the most promising cancer immunotherapies — tire out when engaged in prolonged battles against the cancer. The new smart cells stay consistently strong through the entire fight, conserving their energy by switching to a standby mode when not directly engaged with the cancer.

“These findings address all critical challenges that have been in the way of developing immunotherapies for patients who suffer from these cancers,” said Okada, who also serves as director of the Brain Tumor Immunotherapy Center at UCSF. “This science is ready to move towards clinical trials.”

Expanding Immunotherapies to Deadly Brain Cancers
Glioblastomas are a particularly tragic case in which patients so far haven’t been able to benefit from CAR-T cells. Every year, over 20,000 adults in the United States are diagnosed with glioblastoma or other types of malignant brain cancer, and with current treatments, the prognosis is grim.
“It’s like a death sentence,” says Okada, noting that brain tumors are also the leading cause of cancer-related mortality and morbidity in children. “The outcome for malignant brain tumors in kids remains dismal.” Okada, who is an expert in brain cancers, partnered with Lim, who was developing novel cell engineering technologies, in the hopes of changing this.

Previous work had identified a molecule that is frequently found on glioblastoma cells, giving researchers hope that CAR-T cells could target this molecule and do away with the deadly cancer. Though this strategy was effective in killing some glioblastoma cells, not all glioblastoma cells display this molecule. This allowed some cancer cells to evade the CAR-T therapy and eventually resulted in the cancer’s return.

Targeting other molecules came with the opposite, but equally perilous problem. Though some molecules are found on glioblastoma cells, they’re also found on healthy, non-brain tissues such as the liver, kidney, esophagus and genital organs. Targeting cells that display these molecules with CAR-T could damage healthy tissue and put patients in danger. This catch-22 leaves clinicians without an ideal molecular target, a pervasive problem that has thwarted CAR-T’s use in most solid tumors.

The scientists devised a solution to this problem by employing a system called synNotch, a customizable molecular detector that Lim’s lab has been perfecting for several years. The synNotch system lets scientists program CAR-T cells to detect specific molecules found on the surface of cancer cells, ensuring that CAR-Ts attack only when they encounter the molecules they’re programmed to target.

To kill glioblastomas, the team took a novel, two-step approach. The first step uses synNotch to give CAR-Ts the ability to carefully judge if they are in a tumor versus other parts of the body, while a second set of synNotch sensors ensures a strong and comprehensive tumor killing response. Once the CAR-T cells confirm that they are in the tumor, the second set of sensors are activated, allowing the CAR-Ts to detect and kill glioblastoma cells based on multiple brain-tumor molecules. This two-step process leads to more complete tumor killing and prevents tumor cells from accumulating simple mutations that would allow them to evade CAR-Ts.

Experiments described in the paper show that this strategy is effective. In mice with human patient-derived glioblastomas, synNotch CAR-Ts wiped out tumors that weren’t cleared by normal T-cells or traditional CAR-Ts, with no signs of dangerous side effects.

“We’ve been saying for a while that we should think of these cells like computers — smart enough to integrate multiple data points and make complex choices,” said Lim, who also directs the Cell Design Institute at UCSF. “Now we’re seeing this working in a real-world model of a very deadly cancer for both adults and children.”

SynNotch Is a Flexible, Powerful System for Building Smarter Immunotherapies
The second paper further demonstrated the efficacy of this approach by identifying additional molecular targets for the synNotch system. The researchers searched public cancer databases for molecules found in tumor cells that could be useful in CAR-T therapies against now-intractable diseases. They found a molecule called ALPPL2 that’s common to many forms of cancer, including the asbestos-driven mesothelioma as well as ovarian, pancreatic and testicular malignancies. Importantly, the molecule is rarely found in healthy tissue.

In tests of synNotch circuits that were engineered to detect ALPPL2, CAR-T cells were able to recognize and kill mesothelioma and ovarian cancer cells with precision. “We can build cells that recognize ALPPL2 and then upregulate other sensors against more general tumor antigens,” said Roybal, also a founding member of the Cell Design Institute. “This is a completely viable, clinical grade antigen we can use to build cell therapies for use in people.”

A striking finding from both studies is that synNotch CAR-Ts maintained stable levels of activity throughout the cancer killing process, eliminating the challenge of T-cell exhaustion, which hinders traditional CAR-T therapies. Researchers believe exhaustion occurs because traditional CAR-Ts are designed to continuously express a kill switch, meaning they are always on and eventually deplete their resources, leading to a “cell that isn’t doing much of anything,” Roybal said.

“Amazingly this wasn’t the case in our synNotch systems,” he said. The researchers found that synNotch CAR-T cells remain in standby mode until they identify the cancer, conserving their energy. “These papers show that there are a variety of reasons these synNotch T-cells could be better than the current state-of-the-art CAR-T cell technology.”










 

2021 Retreat Registration Forms Are Here!

 

It's that time of year! If you are interested in applying for a spot at the retreat, please fill out the three forms you will find by clicking the link below.

You can either email the forms to mastrangelom@comcast.net or you can print, fill out and then mail the PDF forms to: 

Margaret Mastrangelo
4 East Commons Dr.
Hadley, MA 01035

The three forms are available by clicking on the following link:

2021 TTT Registration Forms

There you will find the instructions for the application, as well as three documents that will need to be completed and returned in order for your application to be accepted for review. 

To complete these forms online and return via email:

  • Once you click on the above link, right click "TTT 2021 Registration Forms" at the top of the page. 



  • Click "Download"
  • Complete the forms through your PDF viewer OR print the forms and fill out by hand to send.
  • If you complete your forms on your computer, email them to: mastrangelom@comcast.net
  • If you complete your forms by hand, you can:
    • mail to:
Margaret Mastrangelo
Hadley, MA 01035
4 East Commons Dr.


  • Scan and email your documents to: 
mastrangelom@comcast.net


Friday, June 11, 2021

Survivor Relief Fund


 The National Ovarian Cancer Coalition offers the following. See NOCC website for further details.

NOCC Survivor Relief Fund

The Reality: Here & Now
Times have changed, ovarian cancer has not.

"Although the world around us looks a little different these days, one thing that will never change is our commitment to you, our NOCC community. You will remain at the heart of everything that we do - it is just that simple"
Melissa Aucoin, Chief Executive Officer

Our community needs our support now more than ever. Women and their families are facing significant hurdles beyond their ovarian cancer diagnosis and treatment - they are confronting additional concerns that are weighing heavily on their minds during this health crisis. After speaking with our community, we learned that there are two areas where we can provide support assistance and relieve added stress caused by COVID-19.

The Future: We are Here for You Now & Always
We are pleased to announce the launch of the National Ovarian Cancer Coalition Survivor Relief Fund to deliver support services to our Survivors and Caregivers through two additional programs that assist with financial burden and hardship during these difficult times. 

  • Teal Comfort for the Soul
    No women should have to worry about making sure they have a warm meal on the table when dealing with ovarian cancer. With this program, we will ensure quality prepared food will be delivered weekly. Teal Comfort for the Soul will allow our community with compromised immune systems to stay home and receive healthy meals at their doorstep. 
  • Teal Comfort for the Mind
    We understand the stress of a new diagnosis, the anxiety of a recurrence, or the pressures that come from being a Caregiver can be emotionally overwhelming. We have partnered with BetterHelp to provide emotional support to anyone impacted by ovarian cancer. This opportunity includes a subscription with access to one-on-one licensed counselor sessions. Survivors and loved ones can connect with their counselor through a variety of ways; phone, video, live chat, or text in the comfort of their own home.