FDA Approves First CAR-T Cell Therapy for Pediatric Acute Lymphoblastic Leukemia

Emily Whitehead

Caption: Cancer survivor Emily Whitehead with her dog Lucy.
Credit: Emily Whitehead Foundation

Tremendous progress continues to be made against the Emperor of All Maladies, cancer. One of the most exciting areas of progress involves immunotherapy, a treatment strategy that harnesses the natural ability of the body’s own immune cells to attack and kill tumor cells. A lot of extremely hard work has gone into this research, so I was thrilled to learn that the Food and Drug Administration (FDA) just announced today its first approval of a promising type of immunotherapy called CAR-T cell therapy for kids and young adults with B-cell acute lymphoblastic leukemia (ALL)—the most common childhood cancer in the U.S.

ALL is a cancer of white blood cells called lymphocytes. Its treatment with chemotherapy drugs, developed with NIH support, has transformed ALL’s prognosis in kids from often fatal to largely treatable: about 90 percent of young patients now recover. But for those for whom the treatment fails, the prognosis is grim.

In the spring of 2012, Emily Whitehead of Philipsburg, PA was one such patient. The little girl was deathly ill, and her parents were worried they’d run out of options. That’s when doctors at Children’s Hospital of Philadelphia gave Emily and her parents new hope. Carl June and his team had successfully treated three adults with their version of CAR-T cell therapy, which is grounded in initial basic research supported by NIH [1,2]. Moving forward with additional clinical tests, they treated Emily—their first pediatric patient—that April. For a while, it was touch and go, and Emily almost died. But by May 2012, her cancer was in remission. Today, five years later, 12-year-old Emily remains cancer free and is thriving. And I’ve had the great privilege of getting to know Emily and her parents over the last few years.

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Snapshots of Life: Fighting Urinary Tract Infections

Urinary tract infection in a mouse

Source: Valerie O’Brien, Matthew Joens, Scott J. Hultgren, James A.J. Fitzpatrick, Washington University, St. Louis

For patients who’ve succeeded in knocking out a bad urinary tract infection (UTI) with antibiotic treatment, it’s frustrating to have that uncomfortable burning sensation flare back up. Researchers are hopeful that this striking work of science and art can help them better understand why severe UTIs leave people at greater risk of subsequent infection, as well as find ways to stop the vicious cycle.

Here you see the bladder (blue) of a laboratory mouse that was re-infected 24 hours earlier with the bacterium Escherichia coli (pink), a common cause of UTIs. White blood cells (yellow) reach out with what appear to be stringy extracellular traps to immobilize and kill the bacteria.

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Regenerative Medicine: Making Blood Stem Cells in the Lab

Endothelial cells becoming hematopoietic stem cells

Caption: Arrow in first panel points to an endothelial cell induced to become hematopoietic stem cell (HSC). Second and third panels show the expansion of HSCs over time.
Credit: Raphael Lis, Weill Cornell Medicine, New York, NY

Bone marrow transplants offer a way to cure leukemia, sickle cell disease, and a variety of other life-threatening blood disorders.There are two major problems, however: One is many patients don’t have a well-matched donor to provide the marrow needed to reconstitute their blood with healthy cells. Another is even with a well-matched donor, rejection or graft versus host disease can occur, and lifelong immunosuppression may be needed.

A much more powerful option would be to develop a means for every patient to serve as their own bone marrow donor. To address this challenge, researchers have been trying to develop reliable, lab-based methods for making the vital, blood-producing component of bone marrow: hematopoietic stem cells (HSCs).

Two new studies by NIH-funded research teams bring us closer to achieving this feat. In the first study, researchers developed a biochemical “recipe” to produce HSC-like cells from human induced pluripotent stem cells (iPSCs), which were derived from mature skin cells. In the second, researchers employed another approach to convert mature mouse endothelial cells, which line the inside of blood vessels, directly into self-renewing HSCs. When these HSCs were transplanted into mice, they fully reconstituted the animals’ blood systems with healthy red and white blood cells.

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Snapshots of Life: Host vs. Pathogen

Cryptoccocus neoformans

Caption: This scanning electron microscopy image shows mouse macrophages (green) interacting with a fungal cell (blue).
Credit: Sabriya Stukes and Hillary Guzik, Albert Einstein College of Medicine

Macrophages are white blood cells that generally destroy foreign invaders by engulfing them. It’s a tried-and-true strategy, but it doesn’t always work. Cryptoccocus neoformans, a deadly fungal pathogen commonly found in the feces of pigeons, can foil even the best macrophages. No one has captured this grand escape—but researchers are getting a whole lot closer to doing so.

Sabriya Stukes, an NIH-funded microbiologist at New York’s Albert Einstein College of Medicine, studies the interactions between C. neoformans and macrophages to determine how the former causes the lung infection cryptococcosis, which can be deadly for people with compromised immune systems. Stukes believes what makes C. neoformans so dangerous is that it can survive the acid death chamber inside macrophages—a situation that spells doom for most other pathogens. A big reason behind this fungus’s power of survival is its thick coat of polysaccharides, which serves as woolly-looking armor. Once a macrophage engulfs the fungus, this coat can give the white blood cell “indigestion,” prompting it to spit the fungus back into the lungs where it can cause disease.  Continue reading

Shattering News: How Chromothripsis Cured a Rare Disease

Karyotype

Caption: Karyotype of a woman spontaneously cured of WHIM syndrome. These chromosome pairings, which are from her white blood cells, show a normal chromosome 2 on the left, and a truncated chromosome 2 on the right.
Source: National Institute of Allergy and Infectious Diseases , NIH

The world of biomedical research is filled with surprises. Here’s a remarkable one published recently in the journal Cell [1]. A child born in the 1950s with a rare genetic immunodeficiency syndrome amazingly cured herself years later when part of one of her chromosomes spontaneously shattered into 18 pieces during replication of a blood stem cell. The damaged chromosome randomly reassembled, sort of like piecing together a broken vase, but it was still missing a shard of 164 genes—including the very gene that caused her condition.

Researchers say the chromosomal shattering probably took place in a cell in the bone marrow. The stem cell, now without the disease-causing gene, repopulated her immune system with healthy bone marrow-derived immune cells, resulting in cure of the syndrome.

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