For children, young adults with recurrent AML, immunotherapy shows
promise
Natural killer cells could help young patients with few treatment options


Date:
December 14, 2021
Source:
Washington University School of Medicine
Summary:
Researchers have shown, in a small clinical trial, that an
immunotherapy harnessing pre-activated natural killer cells can
help some children and young adults with recurrent AML and few
other treatment options.



FULL STORY ==========================================================================
An immunotherapy harnessing the immune system's "natural killer" cells
has proven effective in treating acute myeloid leukemia (AML) in some
adults whose cancers return. Now, researchers at Washington University
School of Medicine in St. Louis have shown, in a small clinical trial,
that the same natural killer cells also can help some children and young
adults with recurrent AML and few other treatment options.


========================================================================== Results from the phase 1 trial, which included eight patients ages 1 to
30 years, are published online in the journal Blood.

"All of the patients enrolled in this study had very aggressive AML,"
said first author Jeffrey J. Bednarski, MD, PhD, an assistant professor
of pediatrics. "For all of them, their leukemia recurred after stem cell transplantation and was not responsive to several treatment regimens
before they were referred to this study. This is a very challenging
disease to treat - - none of the patients had any curative options. The survival expectation for these patients was essentially zero. That three patients are still alive is very encouraging for this really challenging disease." Acute myeloid leukemia is a cancer of the blood and bone
marrow that results in the overproduction of immature white blood
cells, which crowd out healthy blood cells. Standard therapy involves chemotherapy and a stem cell transplant from a donor, which can result in
a long-term remission. But for patients whose cancers return after stem
cell transplantation, the disease becomes extremely difficult to treat,
and most patients ultimately die from progression of their disease within
a few months to a year.

Of the eight patients who received the investigational treatment, four
achieved complete remission by day 28 after therapy. Two of the four
stayed in remission for more than three months. One of these patients
remains in remission today, more than two years after the treatment. Three patients who went into remission later relapsed. Of those three, two were
able to receive a second stem cell transplant, and they're still alive
and doing well. Two other patients had a partial response to the therapy,
in that their disease decreased, but they did not go into remission. The remaining two patients did not respond to the therapy.

"We found that the donor's natural killer cells expanded, persisted and remained highly active against the leukemia in most of the patients for
over three months," said Bednarski, who treats patients in the pediatric
cancer program at Siteman Kids at St. Louis Children's Hospital and
Washington University School of Medicine. "This therapy also was very
well tolerated by the patients, who experienced almost no toxicities."
Natural killer cells are a type of immune cell that attacks foreign or compromised cells, including bacteria, virus-infected cells and even
cancer cells. Past work from Washington University researchers has shown
that natural killer cells' ability to attack cancer cells can be enhanced
by exposing them to a specific cocktail of chemicals called cytokines. The natural killer cells are collected from a donor and then exposed in the
lab to three cytokines called interleukins 12, 15 and 18. This exposure activates the cells and prompts them to remember this activation. When
such "cytokine-induced memory- like" natural killer cells are given to
the patient, they are more aggressive in attacking the cancer because
of this pre-activation.

"A unique angle to this study is that we're using the patient's original
stem cell donor's cells to generate the memory-like natural killer cells,
so the cells won't be rejected by the patient's immune system but are
still able to fight the leukemia," said senior author Todd A. Fehniger,
MD, PhD, a professor of medicine who treats patients at Siteman Cancer
Center at Barnes-Jewish Hospital and Washington University School of
Medicine. "We're also pleased to see evidence that these cells are
extremely safe. They do not have the severe side effects that are
sometimes seen in cellular therapies based on T cells.

Using cutting-edge science within this trial, we also now understand
these memory-like natural killer cells are very unique, even compared with conventional natural killer cells." Fehniger's lab developed the methods
for producing the cytokine-induced memory- like natural killer cells
and led the original clinical trial of these cells in adults with AML.

Based on the experience of these eight patients, the investigators are
making some changes to the protocol in an effort to make the treatment
more effective for future patients. Bednarski said they will combine
the memory-like natural killer cells with different chemotherapies to investigate whether that can optimize the killing of leukemia cells. They
also will add a second infusion of the memory-like natural killer cells
to extend the amount of time that the cells have to expand in the body
and kill the leukemia cells.

"We plan to treat a larger group of pediatric and adult patients using
this approach in an ongoing study," Fehniger said. "Memory-like natural
killer cells also are being explored as an experimental treatment
for other cancers, including solid tumors such as melanoma and head
and neck cancers, which are really exciting advancements in the field." ========================================================================== Story Source: Materials provided by
Washington_University_School_of_Medicine. Original written by Julia
Evangelou Strait. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jeffrey J Bednarski, Clare Zimmerman, Melissa M Berrien-Elliott,
Jennifer
A Foltz, Michelle Becker-Hapak, Carly C Neal, Mark Foster,
Timothy Schappe, Ethan McClain, Patrick Pence, Sweta Desai,
Samantha Kersting- Schadek, Pamela Wong, David A. Russler-Germain,
Bryan Fisk, Wen-Rong Lie, Jeremy Eisele, Stephanie Hyde, Sima T
Bhatt, Obi L. Griffith, Malachi Griffith, Allegra A Petti, Amanda
F. Cashen, Todd A Fehniger. Donor Memory-like NK cells Persist and
Induce Remissions in Pediatric Patients with Relapsed AML after
Transplant. Blood, 2021; DOI: 10.1182/ blood.2021013972 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211214104248.htm

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