One step closer to making ‘off-the-shelf’ immune cell therapy for cancer a reality 

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Immunotherapy is a type of cancer treatment that uses a person’s own immune system to fight cancer. It comes in a variety of forms including targeted antibodies, cancer vaccines, and adoptive cell therapies. While immunotherapies have revolutionized the treatment of aggressive cancers in recent decades, they must be created on a patient-specific basis and as a result can be time consuming to manufacture/process and incredibly costly to patients already bearing the incalculable human cost of suffering from the cruelest disease.

Fortunately, the rapid progress that has led to the present era of cancer immunotherapy is expected to continue as scientists look for ways to improve efficacy and reduce cost. Just this week, a CIRM-funded study published in Cell Reports Medicine revealed a critical step forward in the development of an “off-the-shelf” cancer immunotherapy by researchers at UCLA. “We want cell therapies that can be mass-produced, frozen and shipped to hospitals around the world,” explains Lili Yang, the study’s senior author. 

Lili Yang, the study’s senior author and a member of UCLA’s Broad Stem Cell Research Center

In order to fulfil this ambitious goal, Yang and her colleagues developed a new method for producing large numbers of a specialized T cell known as invariant natural killer T (iNKT) cells. iNKT cells are rare but powerful immune cells that don’t carry the risk of graft-versus-host disease, which occurs when transplanted cells attack a recipient’s body, making them better suited to treat a wide range of patients with various cancers.

Using stem cells from donor cord-blood and peripheral blood samples, the team of researchers discovered that one cord blood donation could produce up to 5,000 doses of the therapy and one peripheral blood donation could produce up to 300,000 doses. The high yield of the resulting cells, called hematopoietic stem cell-engineered iNKT (HSC–iNKT) cells,could dramatically reduce the cost of producing immune cell products in the future. 

In order to test the efficacy of the HSC–iNKT cells, researchers conducted two very important tests. First, they compared its cancer fighting abilities to another set of immune cells called natural killer cells. The results were promising. The HSC–iNKT cells were significantly better at killing several types of tumor cells such as leukemia, melanoma, and lung cancer. Then, the HSC–iNKT cells were frozen and thawed, just as they would be if they were to one day become an off-the-shelf cell therapy. Researchers were once again delighted when they discovered that the HSC–iNKT cells sustained their tumor-killing efficacy.

Next, Yang and her team added a chimeric antigen receptor (CAR) to the HSC–iNKT cells. CAR is a specialized molecule that can enable immune cells to recognize and kill a specific type of cancer. When tested in the lab, researchers found that CAR-equipped HSC–iNKT cells eliminated the specific cancerous tumors they were programmed to destroy. 

This study was made possible in part by three grants from CIRM.

New model unlocks clues to treating deadly childhood cancer

CIRM-funded research at Sanford Burnham Prebys Medical Discovery Institute in San Diego is identifying compounds that could be used to help children battling a deadly brain cancer.

The cancer is choroid plexus carcinoma (CPC), a rare brain tumor that occurs mainly in children. As it grows the tumor can affect nearby parts of the brain resulting in nausea, vomiting and headaches.

Treatment involves surgery to remove the tumor followed by chemotherapy and radiation. However, many of the children are too young to undergo radiation and only around 40 percent are still alive five years after being diagnosed. Even those who do survive often experience life-long consequences such as developmental disabilities.

One obstacle to developing better therapies has been the lack of a good animal model to enhance our understanding of the disease. That’s where this later research, published in the journal Cancer Research, comes in.

The team at Sanford Burnham developed a new mouse model, by knocking out p53, a gene known to suppress tumor formation, and activating a gene called Myc, which is known to cause cancer.  

Robert Wechsler-Reya

In a news release, Robert Wechsler-Reya, the senior author of the paper, says this new model mirrors the way CPC grows and develops in humans.

“This model is a valuable tool that will increase our understanding of the biology of the cancer and allow us to identify and test novel approaches to therapy. This advance brings us one step closer to a future where every child survives—and thrives—after diagnosis with CPC.”

As proof of that the team tested nearly 8,000 compounds against the mouse tumor cells, to see if they could help stop or slow the progression of the disease. They identified three that showed potential of not just stopping the cancer, but of also not harming healthy surrounding cells.

“These compounds are promising, much-needed leads in the quest for an effective CPC treatment,” says Wechsler-Reya. “Our laboratory plans to evaluate these and additional compounds that can effectively treat this cancer.”

Newest member of CIRM Board is a fan of horses, Star Trek and Harry Potter – oh, and she just happens to be a brilliant cancer researcher too.

malkas-linda

An addition to the family is always a cause for celebration, whether it be a new baby, a puppy, or, in our case, a new Board member. That’s why we are delighted to welcome City of Hope’s Linda Malkas, Ph.D., as the newest member of the CIRM Board.

Dr. Malkas has a number of titles including Professor of Molecular and Cellular Biology at Beckman Research Institute; Deputy Director of Basic Research, Comprehensive Cancer Center, City of Hope; and joint head of the Molecular Oncology Program at the Cancer Center.

Her research focus is cancer and she has a pretty impressive track record in the areas of human cell DNA replication/repair, cancer cell biomarker and therapeutic target discovery. As evidence of that, she discovered a molecule that can inhibit certain activities in cancerous cells and hopes to move that into clinical trials in the near future.

California Treasure John Chiang made the appointment saying Dr. Malkas is “extraordinarily well qualified” for the role. It’s hard to disagree. She has a pretty impressive resume:

  • She served for five years on a National Cancer Institute (NCI) subcommittee reviewing cancer center designations.
  • She has served as chair on several NCI study panels and recently took on an advisory role on drug approval policy with the Food and Drug Administration.
  • She has published more than 75 peer-reviewed articles
  • She sits on the editorial boards of several high profile medical journals.

In a news release Dr. Malkas says she’s honored to be chosen to be on the Board:

“The research and technologies developed through this agency has benefited the health of not only Californians but the nation and world itself. I am excited to see what the future holds for the work of this agency.”

With all this in her work life it’s hard to imagine she has time for a life outside of the lab, and yet she does. She has four horses that she loves to ride – not all at the same time we hope – a family, friends, dogs and cats she likes spending time with. And as if that wasn’t enough to make you want to get to know her, she’s a huge fan of Star Trek, vintage sci-fi movies and Harry Potter.

Now that’s what I call a well-rounded individual. We are delighted to have her join the CIRM Team and look forward to getting her views on who are the greater villains, Klingons or Death Eaters.