Immuno-Oncology: Modulating the Immune Response Against Cancer Cells

By: Dr. Stephen Pelsue Overview Neoplasia, or cancer, comes from the Greek meaning “new growth.”  Malignant neoplasms are unrestrained and spread into the surrounding tissue which may lead to physiological impairment.  The “new growth” is a result of genetic changes that limit the effectiveness of normal cell cycle checkpoints and growth parameters.  In many cases, the altered gene expression of the preneoplastic or neoplastic cell can be detected by the immune system through immune surveillance mechanisms which will then target the defective cells and remove them and prevent any harm to the host.  However, continual mutation and adaption of the
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Categories: Technical Blog.

Some Good News in the Fight Against Cancer

By: Dr. Stephen Pelsue Cancer is caused by the unregulated growth of cells due to genetic alterations. Cancer can be a devastating disease and is seemingly indiscriminate. Due to recent advances in prevention, detection, and treatment; cancer rates have been declining over the last several decades. February is Cancer Prevention Month, so I thought I would highlight a recent report published by the American Cancer Society  (Cancer Statistics, 2016) which has some good news in the fight against cancer. I think the biggest take away from the ACS report is that the overall death rate from cancer has dropped 23%
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Categories: Technical Blog.

Beyond Germinal Center B Cells: Developing Memory and Antibody Producing Plasma Cells

By: Dr. Stephen Pelsue I. Overview The primary function of a B cell is to produce antibodies. As we have previously discussed, B cell development is linked to immunoglobulin (antibody) gene rearrangement, and development of (high affinity) antibody specificity is generated through affinity maturation. Affinity maturation takes place in the germinal center and the result of this process is the generation of B cell populations that produce antibodies and memory. In this article, we will explore what happens to activate memory and antibody production following the affinity maturation in the germinal center. II. Review of the Germinal Center Before we
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Categories: Technical Blog.

Antigen Presentation: The Gift that Keeps on Giving

By: Dr. Stephen Pelsue I. Overview As we enter the season of giving (and receiving), I thought it would be a great time to consider how antigens are presented to the immune system. A robust adaptive immune response is driven by antigen stimulation of both B cells and T cells. While both cellular populations are activated by the same antigen(s), they engage the antigen quite differently. In past articles I have spent a great deal of time discussing B cell receptor (BCR)/ antibody development and maturation, diversity, and their ability to develop specificity to antigens. However, I have yet to describe
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Categories: Technical Blog.

Detection of Therapeutic Antibodies Using Anti-Idiotype Antibody Immunoassays

By: Dr. Stephen Pelsue I. Overview As we discussed in the last blog, antibodies have become an important part of the therapeutics landscape. During the pre-clinical and clinical evaluation stages, detection of the antibody drug is critical to evaluate dose, toxicity, and efficacy. Remember, the antibody drug has been developed to “look” identical, or as much as possible, to natural human antibodies in order to prevent adverse effects in patients. This poses a particular problem in the development of assays to characterize the drug, as it requires the specific detection of a single antibody (the drug), typically at a concentration
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Categories: Technical Blog.

Therapeutic Antibodies

By: Dr. Stephen Pelsue I. Brief Overview of Historical Uses of Antibodies Used for Therapeutic Purposes While we tend to think about the use of antibodies for therapeutic purposes as a relatively recent development, in fact, animal antisera for protection against diphtheria dates back to the 1890s. The uses of animal antisera to provide passive immunity provided new treatments, however, due to the use of non-human antisera, the development of serum sickness from the response to the foreign gamma globulins became a significant issue.  Human gamma globulin therapies were developed in the 1940s to provide protection to immunodeficient and immunocompromised
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Categories: Technical Blog.

Antigen Design: Considering the Target

By: Dr. Stephen Pelsue I. Overview Up to this point we have focused much of our attention on the development, structure, and applications of antibodies – after all the blog is called the “Biology of Antibodies.”  In this blog post, we are going to switch perspectives and think a little bit about the antigen.  An antigen is any structure that can be recognized by an antibody, however the binding of the antigen to an antigen receptor (membrane bound antibody) does not necessarily lead to the lymphocyte activation and the development of an immune response.  A substance that has the ability
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Categories: Technical Blog.

Fundamentals of Immunoassays

By: Dr. Stephen Pelsue I. Overview The discovery of antibodies by Paul Ehrlich in 1900 immediately led to the use of antibodies for the detection and analysis of specific compounds in complex samples. From the earliest ABO blood typing and precipitin tests, through the more sensitive detection by radioimmunoassays (RIA) and enzyme-linked immunosorbent assay (ELISA), antibodies have been at the heart of immunoassays.  The purpose of this blog post is to focus on the basic role of antibodies and antibody specificity in immunoassay development and detection.  In future blogs I will focus on and discuss specific assay formats and applications,
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Categories: Technical Blog.

Affinity Maturation: The Path to Improving Antibody Binding

By: Dr. Stephen Pelsue, Science Director I. Overview The functionality of an antibody comes down to how well it can recognize a specific structure and how tightly it binds to that structure.  There are two properties that define antibody-antigen associations: affinity and avidity.  Affinity is the specific binding strength between the epitope of the antigen and the paratope (or antigen binding site) of the antibody, while avidity is the measure of the total antibody-antigen complex.  Avidity is dependent on the affinity of a given epitope as well as the valency of the antibody binding sites–an IgG has a antigen binding
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Categories: Technical Blog.

Lupus Awareness Month: When Antibodies Go Rogue

By: Dr. Stephen Pelsue, Science Director May is Lupus awareness month and May 10th is World Lupus Day, therefore I would like to use this blog post to discuss a slightly different aspect of antibodies. So far we have considered the functionality of antibodies as part of the host defense mechanism; as well as their utility in research, diagnostics, and as therapeutics.  However, antibodies can also participate in disease pathology and most notably in autoimmune diseases.  Autoimmune diseases occur when the immune system attacks self and generates a chronic inflammatory condition that leads to tissue damage. Lupus is one such
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Categories: Technical Blog.