Revolutionary Immunotherapy: CAR T-Cell Therapy

What happens in CAR T-Cell Therapy when T cells attack cancer cells
Electron micrograph of T cells (red) attacking cancer cells (white). Source: National Cancer Institute Duncan Comprehensive Cancer Center at Baylor College of Medicine

Imagine being able to program your immune system to launch one million minuscule heat-seeking missiles, whose sole purpose is to find and kill cancer cells.  This is the basic premise behind an emerging form of immunotherapy, called CAR T-cell therapy, which genetically modifies an individual’s immune system to find, bind to, and kill cancer cells.

The evolution of CAR T-Cell Therapy

A recent FDA approval of CAR T-cell therapy in childhood leukemia has put this breakthrough approach in the spotlight.  NETRF has funded multiple research studies on CAR T-cell therapy in NETs since 2014. The Foundation’s first grant was to a pioneer of this therapy Carl June, M.D., and his colleagues Xianxin Hua, M.D., Ph.D., and David Metz, M.D., at the University of Pennsylvania. These colleagues continue to collaborate on NET research, with Dr. Hua leading an ongoing study.

“These recent advances raise an exciting possibility that NETs can be specifically targeted via specific CAR T cells to effectively eradicate NET cells,” said Xianxin Hua, M.D., Ph.D.

Most of the early CAR T-cell research focused on blood cancers, especially lymphoiblast leukemia, because these leukemia cells express a highly lineage-specific cell surface antigen that can be targeted by CAR T cells to eradicate the antigen-bearing cells including the leukemia cells. While NET cancer cells do not express a NET cell-specific cell surface antigen, NET cells tend to express abnormally high levels of somatostatin receptors (SSTRs) on their surface. Researchers hope that SSTR can serve as the antigen that attracts the killer CAR T cells.

What is CAR T-Cell Therapy?

CAR T cells are engineered to produce special receptors on their surfaces. They are then expanded in the laboratory and returned to the patient. Credit: National Cancer Institute

As its name implies, the backbone of CAR T-cell therapy is genetically engineered T cells, which work as the workhorses of the immune system to kill cells with surface antigens that can be specifically recognized by the engineered CAR T cells. The therapy requires drawing blood from patients and separating out the T cells. Next, the T cells are genetically engineered to produce receptors on their surface called chimeric antigen receptor, or CARs, which is tethered to T cell-activating modules. The CAR-expressing T cells, or CAR T cells,  are programmed to cling to the specific antigen found on the surface of the cancer cell.  Then they are “expanded” in the laboratory to created hundreds of millions of cancer-killing cells. The final step is the infusion of the CAR T cells into the patient. If all goes as planned, the engineered cells further multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill cancer cells that harbor the SSTR antigen on their surfaces.

CAR T-Cell Therapy in NETs

The first step in using this technology in NETs is to develop receptors to recognize SSTR as an antigen on surface of the neuroendocrine tumor cell.  Dr. Hua and colleagues have developed a CAR system that can attach to SSTR-expressing tumor cells and kill the cancer cell. They have successfully tested the receptors in cultures, laboratory models, and are preparing next to test them in freshly isolated human tumor cells.

“These studies will likely lead to the development of an entirely new and more effective therapy for NET patients who have failed previous treatments and save their life,” said Dr. Hua.

Learn more about NETRF-funded research.  Support research to cure NETs.

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Shelly

This is the most exciting news I believe I’ve ever heard. Especially when I haven’t been to a specialist, and as pretty much all NET patients experience, is continuance frustration at the lack of research Oncologists do regarding Neuroendocrine cancer. I was diagnosed with PNets in Oct 2011. I have reached out to a specialist in CO and plan to go see him. Will Car T be able to be used for all types of NETs, specifically pancreatic, and will metastasis to the liver be an issue? I guess really what I’m wanting to know is it a possibility not… Read more »

James

Greetings,
I’m a patient (and healthcare provider) with NET’s, liver predominant, post surgery to resect small bowel,, post PPRT at Stanford. I’d like to participate in any trial involving CAT T-Cell therapy. I’d be willing to be a single patient pilot case, and certainly to be added to any mailing list you have for patients and clinical trials. Carcinoid cancer, well differentiated.
Best, James Cooper, Ph.D.

Daiva

I attended the 2014 NET Conference sponsored by Univ. of PENN & NETRF in Phila. Dr. Carl June brilliantly spoke about his CAR T cell immunotherapy and the Foundation’s first grant was then given to Dr. June, and his colleagues at Univ. of Penn. It was an answer to my prayers to have a world leading immunotherapist, Dr. Carl June working on behalf of the NET community for a cure. The recent FDA approval is indeed groundbreaking and optomistic for all of us in need. Dr. June is also in the Leadership of the Parker Institute. I would like to… Read more »

Gail

I was diagnosed with CLL 15 years ago. My white count was 31,000. The oncologist gave 7 years to live. I never went back to him. That was 15 years ago. My count was as high as 73,000. Last month I was checked and my count was 22,000. However, I black and blue easily and I am always tired. I am hoping there is something that will help me before it’s too late. My oncologist has done nothing but monitor my blood count. When a customer told my about the research being done by Dr. Carl June from the University… Read more »

Jodi Casselman

Can you direct us to Dr Hua’s pubs re: CAR-T. I was not successful finding any in PubMed

Daiva Debra Minter

I would like to know if Dr. June & Team @ University of Penn shares his CAR T cell research for NETs with his colleagues @ the Parker Institute where he is also in Leadership – and vice versa. I hope all are sharing information and research to find a cure for NET cancer asap. Thank you!

VICKI

If I have tissue from the Ilium Tumor that was removed. Then you could use it plus added chemistry to allow my own immune system to distroy the 5 remaining NET tumors? Is this correct??

Hila

Hey Donna,
Will this treatment also be suitable for excretory growth? (Gluconoma for example)
And did you start trying it on NET patients?
Thank you

J Halliday

Who do we support financially to get human trial interest? For those of us with love ones with NETs every moment matters. This research and FDA approval for blood disease is miraculous. I have a friend who received the treatment for her blood disease and is cancer free by scientific measurement. I now have a young daughter with liver tumors (pNETS) primary removed. We need activation and those of us in spheres of influence and not in the medical world need to understand how to encourage human trial. Please tell Dr. June, Hua and Metz we are praying to God… Read more »

Hila

Hey Donna,
Is there somthing new?
I’m looking for heel to my mother.
Thank you

John

Is there any update on the progress? I read we will be hearing some news in early 2018

Hila

Hey Donna,
After the presentation of the study, do you intend to start the experiment in humans?
Will there be cooperation with other places in the world?
Waiting for good news
Hila

Karen Staley

Hello,

Are there any updates on human trials with CAR T-cells for NETS? My niece has Grade 3 neuroendocrine tumors in her liver metastasized from her pancreas. Her blood platelets are so low that she can’t be treated with any form of chemotherapy or other treatments. Please let us know as soon as possible as time is of the essence.

Thank you for your great work.

Karen

Karen,

The CAR T-cell therapy research funded by NETRF is still in the early research phases. It is not yet close to being tested in humans. I am sorry this isn’t an option at this point for your niece. There are liver-directed therapies (interventional radiology) that might interest you. https://youtu.be/ieuGuzQ8tMs Hoping for the best for your family, NETRF

Revolutionary Immunotherapy: CAR T-Cell Therapy