Stories about: immunotherapy

Why does a new class of drugs work so well against melanoma?

nivolumab, pembrolizumab and melanoma
Anti-PD-1 antibodies may deliver a one-two punch in melanoma

Recent clinical trials for patients with advanced melanoma have found that a new class of drugs—anti-PD-1 antibodies—can elicit an unprecedented response rate. In the last year, the FDA gave accelerated approval to two anti-PD-1 antibodies, nivolumab and pembrolizumab, for patients with advanced melanoma (including Jimmy Carter) who are no longer responding to other drugs. And there’s growing evidence that this class of drugs may be effective in treating other forms of cancer.

Anti-PD-1 antibodies target a receptor on activated T cells, known as the programmed cell death 1 (PD-1) receptor. Tumor cells stimulate this inhibitory receptor to dodge immune attack, whereas anti-PD-1 antibodies block the same pathway, “waking up” the immune cells so they can attack the cancer. The drugs have been hailed as one of the first cancer immunotherapy success stories.

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Targeting leukemia with a clinical trial of CAR T-cell therapy

relapsed leukemia targeted therapy CAR T-cell immunotherapy

One of the immune system’s basic jobs is to tell “self” from “non-self.” Our cells carry markers that the immune system uses to recognize them as being part of us. Cells that don’t carry those markers—like bacteria and other pathogens—therefore don’t belong.

Cancer cells, however, fall into a gray area. They’re non-self, yet they also bear markers that connote self-ness—one of the reasons the immune system has a hard time “seeing” and reacting to cancer.

Can we focus the immune system’s spotlight on cancer cells? The provisional answer is yes. Research on cancer immunotherapy—treatments that spur an immune response against cancer cells—has boomed in recent years. (The journal Science recognized cancer immunotherapy as its Breakthrough of the Year in 2013.)

And one of the more recent methods—called chimeric antigen receptor (CAR) T-cell therapy—is now in a clinical trial for relapsed or treatment-resistant B-cell acute lymphoblastic leukemia (ALL) at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.

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Food allergies: Turning tolerance back on

Mast cell food allergy
Mast cells don’t simply cause acute allergic reactions. They also turn off immune tolerance. But that could change. (Bruce Blaus/Wikimedia Commons)
Hans Oettgen, MD, PhD, is Associate Chief of the Division of Allergy and Immunology at Boston Children’s Hospital.  He leads a research group investigating mechanisms of allergic diseases.

Not long ago I received a wonderful email from “Sam,” an 18-year-old young man with peanut allergy. He was participating in a clinical trial of oral immunotherapy (OIT) being carried out by colleagues here at Boston Children’s Hospital.

In OIT, patients receive initially minute doses of the food to which they are allergic. Then, over many weeks, they ingest increasing amounts, under close medical monitoring at the hospital.

OIT’s goal is to get patients to tolerate previously allergenic foods by inducing their bodies to produce Treg cells, or regulatory T cells. These are the master controllers of our immune responses, and their actions include suppressing allergic responses to foods. Food ingestion, as in OIT, will eventually induce food-specific Treg cells, but it can be a long and cumbersome process. For Sam, ingesting escalating doses of peanuts proved difficult: His email described frequent reactions ranging from stomachaches and itchiness to difficulty breathing.

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Unmasking brain tumors with gene therapy

Brain tumors like the diffuse, light gray one in this MRI do a remarkably good job of hiding from the immune system. A new treatment based on gene therapy could strip their camouflage away. (Filip Em/Wikimedia Commons)

If there’s anything that tumors are good at, it’s hiding themselves. Not from things like MRIs or CT scans, mind you, but from the immune system. Since a tumor grows from what were at one time normal, healthy cells it’s still “self,” still one of the tissues that makes you you.

“Tumor cells display very subtle differences that distinguish them from healthy cells, but by and large they look the same to your immune system,” says Mark Kieran, a pediatric neuro-oncologist at the Dana-Farber/Children’s Hospital Cancer Center and Children’s Hospital’s Vascular Biology Program. “The question is: How can we unmask tumors so that the immune system can do its job?”

Researchers have worked for years on cancer vaccines aimed at getting the immune system to wake up to the presence of a tumor and turn on it. With a Phase 1 safety trial , Kieran and his colleagues, including Children’s neurosurgical oncologist Lily Goumnerova, are evaluating a different strategy for patients with hard-to-treat brain tumors called malignant gliomas:  They’re giving the tumors a cold.

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