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Clinical Laboratories and Pathology Groups

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Scientists with Francis Crick Institute and Ragon Institute have successfully created human antibodies in vitro that can be made to recognize specific antigens in the human body; Could lead to new treatments for cancer and other infectious diseases

It’s been long-recognized that the ability to design human antibodies customized to recognize specific antigens could be a game-changer in the diagnosis and treatment of many diseases. It would enable the creation of useful new clinical laboratory tests, vaccines, and similar therapeutic modalities.

Now an international research team has published the findings of its novel technique that was developed to generate human antibodies in vitro. The research was conducted at the Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), Harvard, and the Francis Crick Institute in London.

Antibodies and antigens are used in a large number of clinical laboratory and anatomic pathology tests and assays. In many cases, animal antibodies/antigens are used in test kits because they attract and bind to specific human antibodies/antigens that are biomarkers for diagnoses. Thus, as this technology is validated and further developed, it could be the source of useful biomarkers for lab tests as well as for vaccines.

Antibodies—also referred to as immunoglobulins—are made by the body’s B-lymphocytes (B cells) in response to antigens, such as bacteria, viruses, or other harmful substances. Each antibody has a special bearing on a particular antigen. For example, the human immunodeficiency virus (HIV) antibody and HIV antigen (p24) test screens and diagnoses people for HIV infection, explained LabTestsOnline.

Many medical laboratory tests use animal antibodies and antigens. But what if human antibodies could be generated and stimulated to recognize specific human antigens? That’s what the researchers believe they have done, according to a press release.

The Ragon Institute at MGH, MIT, and Harvard (above) was established in 2009 to find an HIV vaccine and to be a worldwide leader in the study of immunology. The Francis Crick Institute, formed in 2015, is a biomedical research institute using biology to understand health and disease. (Photo copyright: The Ragon Institute.)

The researchers know the novel technique they developed for generating human antibodies in vitro needs further development and validation. If this happens, the technique could one day be the source of useful biomarkers for medical lab tests, and may be a way to prevent infectious diseases.

“Specifically, it should allow the production of these antibodies within a shorter time frame in vitro and without the need for vaccination or blood/serum donation from recently infected or vaccinated individuals,” said Facundo D. Batista, PhD, in the press release. Batista is Principle Investigator with the Ragon Institute and led the research teams. “In addition, our method offers the potential to accelerate the development of new vaccines by allowing the efficient evaluation of candidate target antigens.”

Researchers Aim to Make Human Antibodies in Medical Laboratory

This international team of researchers sought to replicate in the lab—using patient blood samples—a natural human process for creation of antibodies from B cells. This is the process they wished to replicate:

·       Antibodies are made by the body’s B cells;

·       An antigen molecule is recognized by a B cell;

·       Plasma cells (able to secrete antibodies) develop;

·       An antibody binds to a particular antigen to fight an infection.

“B lymphocytes (B cells) play a critical role in adaptive immunity, providing protection from pathogens through the production of specific antibodies. B cells recognize and respond to pathogen-derived antigens through surface B cell receptors,” the researchers wrote in The Journal of Experimental Medicine (JEM).

Nanoparticles Key to the Approach

But finding an exact antigen is only one part of the B cell’s job. In the lab, B cells also need a trigger that enables them to grow and develop into plasma cells, which are key to fighting disease, the researchers noted.

“The in vitro activation of B cells in an antigen-dependent manner is difficult to achieve,” the authors stated in the JEM. “To overcome limitations, we developed a novel in vitro strategy to stimulate human B cells with streptavidin nanoparticles conjugated to both CpG and antigen. B cells producing antigen-specific antibodies were identified, quantified, and characterized to determine the antibody repertoire.”

According to the press release, “CpG oligonucleotides internalize into B cells that recognize the specific antigen.”

The statement, which garnered worldwide attention, noted the following steps taken by the researchers:

·       B cells from patient blood samples were isolated;

·       Then, they were treated with tiny nanoparticles coated with both CpG oligonucleotides and the right antigen;

·       These DNA molecules are unique, because they can activate toll-like receptor 9 (TLR9);

·       TLR9 develops into antibody-secreting plasma cells.

Results: Antibodies for Tetanus, Influenza, HIV

This method, according to the scientists, could be used in further research to develop antibodies to treat infectious diseases and cancer.

According to The Times of India,

·       “The team successfully demonstrated their approach using various bacterial and viral antigens, including the tetanus toxoid and proteins from several strains of influenza A;

·       “In each case, the researchers were able to produce specific, high-affinity antibodies in just a few days. Some of the anti-influenza antibodies generated by the technique recognized multiple strains of the virus and were able to neutralize its ability to infect cells;

·       “The procedure does not depend on the donors having been previously exposed to any of these antigens through vaccination or infection; and,

·       “Researchers were able to generate anti-HIV antibodies from B cells isolated from HIV-free patients.”

Research Suggests More Possibilities

While this highly scientific study may not be on the radar of most anatomic pathologists and medical laboratory leaders at the moment, it holds enormous promise to produce cures for infectious disease and more effective cancer treatments. This research project also demonstrates how new techniques using antibodies have the potential to create an entirely new generation of clinical laboratory assays that improve diagnostic accuracy and better inform physicians when they consider the most appropriate therapies for their patients.

—Donna Marie Pocius

Related Information:

Researchers Develop New Method to Generate Human Antibodies

Novel In Vitro Booster Vaccination to Rapidly Generate Antigen-Specific Human Monoclonal Antibodies

Human Antibodies Produced in Lab for First Time