Stories about: antibodies

Protein science 2.0: Amping up antibodies

Institute for Protein Innovation antibody libraries
The Institute for Protein Innovation, launching next week with $15 million in grants and philanthropy, aims to develop comprehensive, open-source libraries of antibodies targeting human proteins.

It began with the proteins. Before Watson and Crick unraveled DNA’s double helix in the 1950s, biochemists snipped, ground and pulverized animal tissues to extract and study proteins, the workhorses of the body.

Then, in 1990, the Human Genome Project launched. It promised to uncover the underpinnings of all human biology and the keys to treating disease. Funding for DNA and RNA tools and studies skyrocketed. Meanwhile, protein science fell behind.

While genomics unveiled a wealth of information, including the identity of genes that lead to disease when mutated, researchers still do not fully understand what all the genes really do and how mutations change their function and cause disease.

Now proteins are promising to provide the missing link.

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Seeding medical innovation: The Technology Development Fund

Monique Yoakim Turk Technology Development FundMonique Yoakim-Turk, PhD, is a partner of the Technology Development Fund and associate director of the Technology and Innovation Development Office at Boston Children’s Hospital

Since 2009, Boston Children’s Hospital has committed $6.2 million to support 58 hospital innovations ranging from therapeutics, diagnostics, medical devices and vaccines to regenerative medicine and healthcare IT projects. What a difference six years makes.

The Technology Development Fund (TDF) was proposed to Boston Children’s senior leadership in 2008 after months of research. As a catalyst fund, the TDF is designed to transform seed-stage academic technologies at the hospital into independently validated, later-stage, high-impact opportunities sought by licensees and investors. In addition to funds, investigators get access to mentors, product development experts and technical support through a network of contract research organizations and development partners. TDF also provides assistance with strategic planning, intellectual property protection, regulatory requirements and business models.

Seeking some “metrics of success” beyond licensing numbers and royalties (which can come a decade or so after a license), I asked recipients of past TDF awards to report back any successes that owed at least in part to data generated with TDF funds. While we expected some of the results, we would have never anticipated such a large impact.

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Biogen Idec wins FDA approval for long-lasting hemophilia drug based on Boston Children’s technology

Alprolix FDA approval recombinant factor IX rFIXFc hemophilia B coagulation
(Courtesy Biogen Idec)
A few weeks ago Vector brought you the backstory of how a clotting factor for hemophilia was made to last longer in the blood, allowing injections to be pared to once every week or two, rather than two to three per week.

Today we bring more good news: Following a successful Phase III trial, rFIXFc recently received the green light for marketing from the FDA and from Health Canada.

Developed by Biogen Idec under the trade name Alprolix™, rFIXFc—a modified version of clotting factor IX—is the fruition of a technology first envisioned by three researchers—gastroenterologists Wayne Lencer, MD, of Boston Children’s Hospital, and Richard Blumberg, MD, of Brigham and Women’s Hospital, and immunologist Neil Simister, DPhil, of Brandeis University—for large protein drugs. Their idea: to extend the drugs’ half-lives by protecting them from being ground up by cells.

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How can we get clotting factors to last longer in the blood?

Meat grinder protecting protein drugs from being ground up by cells clotting factors
Cells can grind up large protein drugs. A new technology may help those drugs escape and stay in the bloodstream longer.
Getting drugs to stay in the bloodstream longer is a big deal when it comes to treating chronic diseases. You see, a drug’s half-life—the time it takes for half of a given dose to be cleared from the body—determines how long its effect(s) last.

If a drug’s half-life is short—meaning it’s cleared quickly—patients will have to take the drug frequently. Given that someone with a chronic condition could be on the medication for many years—say, patients with severe hemophilia, who endure frequent infusions of clotting factors—a short half-life can translate into high cost. Depending on side effects and how the drug is administered, quality of life may also suffer.

Several years ago, Wayne Lencer, MD, a researcher in Boston Children’s Hospital’s Division of Gastroenterology, Hepatology and Nutrition, and his collaborators Richard Blumberg, MD, at Brigham and Women’s Hospital (BWH) and Neil Simister, DPhil, at Brandeis University came up with a way to make protein-based drugs like clotting factors stay in the circulation longer: by keeping cells from grinding them up.

The first drug based on their work—a form of the factor IX clotting factor—just passed a Phase III clinical trial reported in The New England Journal of Medicine.

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Gut microbes teach young B cells. The question is, what are they teaching them?

A necktie with drawings of antibodies
B cells learn early on how to make many kinds of antibodies. What role do microbes in the gut play in teaching them to do so?

Your immune system’s B cells can produce antibodies against an amazing number of pathogens—viruses, bacteria, etc.—without ever having encountered them. That’s because, as they develop, your B cells reshuffle their antibody-producing genes into an amazing number of possible combinations—more than 100 million—to produce what’s called your primary pre-immune B cell repertoire.

It’s long been thought that in people and in mice this reshuffling process—called V(D)J recombination, after the B cells’ antibody-coding V, D and J gene segments—takes place in two places: the bone marrow and the spleen. But new research from a team led by Frederick Alt, PhD, and Duane Wesemann, MD, PhD, suggests that there may be one more place B cells go to undergo recombination: the gut. What’s more, that reshuffling in the gut may be influenced by the microbes that live there.

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Finding the long-sought master switch for antibody diversity

The different gene segments your immune system needs to build a diverse selection of antibodies are spread out across huge genomic distances. Frederick Alt may have found the genetic switch that helps manage all of the far flung pieces. (Jeremy Vandel/Flickr)

Imagine for a moment, that you are your immune system. On any given day, you’re faced with host of threats: a virus here, a bacterium there, a new fungus. And don’t forget those wayward cells lurking around the corner, the ones that might become a tumor.

Now, you have to respond to these challenges, but how you do it? Each looks different, meaning that you have to produce a new T or B cell (your two main tools) that can find, mark and guide the attack against each new threat.

Luckily, your T and B cells can turn to three sets of gene segments that, together, contain the genetic raw material for the variety you need. Called the variable (V), diversity (D) and joining (J) segments, they are constantly cut up, shuffled and rejoined by the genome to make new genes – a process called V(D)J recombination – for new receptors (on T cells) or antibodies (from B cells), giving your immune system the most diverse arsenal possible.

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Toward a flu vaccine that endures through the seasons

While it's not done this way anymore, getting a flu vaccine every year can still be a pain. Stephen Harrison is working on a vaccine strategy that would protect against flu strains from multiple seasons. (Photo: cdc e-health/Flickr)

Every year, the flu tries to outwit humanity. By shifting parts of its outer coat, the virus renders the flu vaccine from the previous year obsolete, bringing another season of misery. And every year, we fight back with a new vaccine, finding a new chink in the virus’s armor and giving ourselves another brief window of protection.

But if Stephen Harrison, chief of Children’s Division of Molecular Medicine, is right, we might be able to train our immune systems to look past the flu virus’s annual trickery and build up resistance that spans multiple seasons. That could reduce the need to develop, produce, and distribute a new flu vaccine nearly every year, a process of selection, growth, packaging, and distribution that can take upwards of seven months.

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