Antibodies are one of the most basic yet precise elements of the immune system: each antibody is associated with a specific antigen that fits to it like a key to a lock, and by binding to the antigen it serves to paint a target on the associated cell for other, more aggressive elements of the immune system to attack. Although antibodies were discovered more than a century ago – German immunologist Paul Ehrlich first coined the term Antikörper in an article he published in 1891—their use as therapeutic agents was limited by our lack of immunological methods.
Enter hybridoma technology. By fusing B-cells that produce the desired antibody with myeloma cells, it became possible to create a colony of hybridomas, all producing antibodies with identical antigen-specificity. Since the technology to humanize these monoclonal antibodies (mAbs) was developed in the late 1980’s, followed by chimeric and ‘fully’ human mAbs, many mAb-based therapies have been developed for a broad range of conditions, from viral to cancerous to inflammatory. However, these antibodies are very fragile and sensitive to temperature, and have to be stored and transported in ultra-low temperatures and sometimes down to liquid nitrogen, so we at Fisher BioServices have proudly had many opportunities to assist in the development and distribution of these biologics-based therapies. Last time, we discussed how cancer cells can be turned against themselves – this time, let’s showcase some of the different ways that monoclonal antibodies are truly Amazing Samples.
Ebola and ZMapp
This year has seen a horrendous spread of the Ebola virus in West Africa. As of last week, the World Health Organization had reported 1,552 deaths, setting the overall mortality rate at more than 50 percent. In response to the outbreak, the FDA last month lifted holds on multiple experimental therapies. One of these, ZMapp (by San Diego’s Mapp Biopharmaceutical), is a plant-derived, humanized monoclonal antibody mixture (with three different mAbs) that had already proven effective in protecting a small population of rhesus monkeys from the virus with 100% success. So far, only very limited quantities of the therapy have been produced and only seven individuals have been treated, but the groups involved are pushing for completion of clinical trials, at which point mass production would become more feasible. One of the individuals who received treatment, Kyndy Kobbah, not only praised its efficiency, but urged Mapp Biopharmaceutical to accelerate the drug’s production. Should ZMapp be approved, we will have a much-needed remedy and hope commercial availability will quickly follow. Read the CDC’s Q&A on experimental treatments and vaccines for the Ebola virus here.
Attacking Cancer from Different Angles
Compared with the immunotherapies discussed last time, many types of monoclonal antibodies are now commercially approved and are readily available as potential therapeutics for various cancers. By mass-producing mAbs specific to certain cancer-related antigens, therapies can potentially be prepared and obtained quickly after diagnosis. The most direct application is use mAbs to give the patient’s immune system ammunition against the disease. Many of these therapies are already approved, and more are in the development pipeline. But some of the applications take quite different approaches, demonstrating the potential versatility that antibody-based therapies can have.
One example is Siamab Therapeutics (formerly Sialix), which is currently developing a panel of mAbs to target a tumor-associated carbohydrate antigen (TACA1), rather than the tumor cell itself. This antigen is associated with most solid tumors (and rarely expressed in normal tissue), and by targeting epitopes within the glycan rather than a more specific glycoprotein, these mAbs may be effective against a broad range of cancer types. Read therir latest publication "Sialic acids sweeten a tumor's life" published on Cancer Research.
Another method that has proven effective is to use a mAb to inhibit the body’s support of tumor development, such as Genentech’s bevacizumab. By binding with vascular endothelial growth factor A (VEGF-A), this mAb prevents tumor growth by inhibiting angiogenesis, and is already in use for treatment of half a dozen types of cancer. FDA approval started with metastatic colorectal cancer, a disease with otherwise depressingly low five-year survival rates (about six percent, according to cancer.org’s information), and was most recently extended to glioblastoma (Mayo Clinic findings video below).
A much newer, still uncommon approach, is supplementing the antibody with a cytotoxic drug, called antibody-drug conjugates (ADCs). This approach greatly reduces the side effects of cytotoxic chemotherapies, by using the antibody to deliver the drug to the cancer cells with a high level of specificity. So far, only three of these ADCs have been approved (see Genentech’s trastuzumab emtansine ADC to treat HER2-positive metastatic breast cancer) but 25 more are in the pipeline at Roche alone. ADCs could redefine chemotherapy by both increasing therapeutic efficiency and reducing the discomfort of patients.
While antibodies are not quite the panacea hoped for a century ago, it’s clear that they are an integral part of the new world of biological therapies. Truly, a vial of monoclonal antibodies is an Amazing Sample.
Share your own story! If you work with, or are conducting research for, a monoclonal antibody therapy, share with us in the comments below!
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