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Immunotherapy: How Antibodies Can Be Used to Treat Diseases

Summary

Grade Range
8th-12th
Group Size
2-3 students
Active Time
90 minutes (Three 20-minute activities)
Total Time
90 minutes
Area of Science
Human Biology & Health
Medical Biotechnology
Key Concepts
Immune system, antibodies, immunotherapy
Credits
Svenja Lohner, PhD, Science Buddies
Drawings of a y-shaped antibody and an infusion bag containing antibodies.

Left: A diagram of an antibody structure. Twelve rectangular shapes connect to make a double-width Y. Middle: A schematic drawing of an infusion bag containing liquid with y-shaped antibodies inside. Right: A tube leads from the infusion bag into a person's arm.

Overview

In this lesson, students will do a series of activities to explore the role of antibodies in our immune system. They will also investigate how doctors use monoclonal antibodies as part of immunotherapy to treat diseases like cancer.

Learning Objectives

Materials

Materials

Background Information for Teachers

This section contains a quick review for teachers of the science and concepts covered in this lesson.

Antibodies are our immune system's highly specialized and ultimate defense weapon against pathogens. When our body comes in contact with foreign substances (antigens), special immune cells called B-cells get triggered to produce antibodies in a process called the adaptive immune response. Antibodies are large y-shaped proteins that identify and neutralize foreign objects, like bacteria or viruses, in our bodies. Each antibody consists of a conserved or constant region and a variable region, as shown in Figure 1. The tips of both y-arms contain variable antigen-binding sites. These are tailored to the specific antigen the immune system is fighting. Once an antibody encounters a matching antigen, it binds to it and flags it for destruction. This process of antibodies fighting a specific pathogen is called the humoral immune response. B-cells continue to produce antibodies until the body is cleared of pathogens and the infection is over.

Two representations of an antibody

On the left, 12 rectangular shapes arranged into a y-shape show the basic structure of an antibody. The rectangles at the tips of the y have indentations representing antigen-binding sites. On the right, squiggly lines arranged into a y-shape respresent a more realistic visualization of the y-shaped protein structure of antibodies.


Figure 1. Schematic drawing (left) and protein structure (right) of an antibody. Image credit: OpenStax College, CC BY 3.0, via Wikimedia Commons

The high binding selectivity of antibodies to a specific target makes them a powerful tool in biotechnology and medicine. They can, for example, be used as probes for diagnostic purposes to identify specific markers, genes, or other materials in laboratory samples. Many home test kits, such as ovulation and pregnancy test kits, use antibodies to selectively bind to and detect specific hormones produced during pregnancy or ovulation.

Antibodies have also become increasingly important in diagnosing and treating diseases such as cancer and Alzheimer's. In recent decades, researchers have found ways to bioengineer antibodies with specific antigen-binding sites. These antigen-binding sites can be designed, for example, to target specific proteins or other disease-causing antigens.

Bioengineered antibodies derived from a single B-cell clone in the laboratory are called monoclonal antibodies (MAbs). Monoclonal antibodies have become powerful medicines for disease prevention and today play a significant role in immunotherapy. Immunotherapy is a medical term that describes any treatment that uses a person's own immune system to fight diseases. This includes the use of monoclonal antibody drugs. It often takes many years of research to develop a new antibody drug. It is a rigorous process with many steps. The most important ones are listed below.

  1. Target discovery: This is usually the first step of the drug development process and includes the identification of potential drug targets in the human body. Potential targets can be any gene, protein, or molecule linked to a particular disease.
  2. Antibody development and testing (preclinical research): Once a potential target has been identified and validated, the next step is developing target-specific antibodies. These antibodies must be tested and optimized.
  3. Clinical trials: The most promising and effective antibody candidates are tested in humans. These trials follow a three-phase process, increasing in scale with every phase.
  4. Drug approval and manufacturing: If the clinical trials are successful, the drug is assessed by the regulatory authorities for its safety and efficacy. Once approval is granted, the large-scale production and distribution of the newly developed antibody drug can begin.

Today there are more than 100 monoclonal antibody drugs on the market. Many of them are used to treat cancer. There are several ways monoclonal antibodies can be used to fight cancer. Some of them are listed below:

  • First, monoclonal antibodies can help the immune system locate cancer cells. By binding to the surface of cancer cells, monoclonal antibodies flag them so they are more easily detected by immune cells and destroyed.
  • Some monoclonal antibodies are used for a more direct attack on cancer cells. Once bound to a cancer cell, these antibodies trigger a series of events inside the cell that cause it to self-destruct.
  • Other antibody drugs prevent cancer cells from growing by binding to and blocking proteins, hormones, or signal molecules necessary for cancer growth and cancer blood vessel formation.
  • Some monoclonal antibody drugs, called antibody-drug conjugates (ADC), deliver cell-killing substances to cancer cells. These substances may include toxins, chemotherapy drugs, or radiation. When these antibodies bind to their target on the surface of the cancer cells, the cell-killing substances linked to the antibody cause the cancer cells to die. The antibody specificity ensures that any cell that does not have the target will not be attacked or harmed.
  • Antibodies can also interact with immune cells directly—for example, by blocking immune system inhibitors, which allows for a more radical immune response against cancer cells.

The following video provides a good overview of the different cancer treatment mechanisms of monoclonal antibodies.

Whereas the specificity of monoclonal antibodies poses a huge opportunity to target specific disease-causing antigens, it also creates limitations for monoclonal antibody drugs. Often, diseases are complex, and targeting just one disease-causing antigen is not enough. More recently, researchers have developed a new type of antibody drug called bispecific antibodies (BsAbs). A bispecific antibody is designed to recognize two different antigens simultaneously. Each antigen-binding site of the two y-arms can bind to a different molecular target. This allows the antibody, for example, to block two different cancer growth factors at the same time. Bispecific antibodies can also be designed to recruit special immune cells and bring them closer to cancer cells. One arm of the antibody binds to a cancer cell, while the other arm binds to a special immune cell called a T-cell, as shown in Figure 2. The proximity to the cancer cell triggers the T-cell to kill the cancer cell.

A y-shaped antibody has a round T cell attached to one of its y-tips, and a round tumor cell attached to its other y-tip.
Figure 2. Bispecific antibodies have two different antigen-binding sites and thus can bind to two different antigens simultaneously. Image credit: Anypodetos, Public domain, via Wikimedia Commons

The first bispecific antibody drug was approved in 2015. Currently, seven bispecific antibody drugs are approved by the regulatory authorities (FDA and EMA), and many more are still in the research pipeline or waiting to be approved. The future of antibody drugs is promising, and developing novel antibody-drug treatments and therapies is part of today's cutting-edge research. Researchers in many biotechnology companies are working hard to develop new technologies to discover new and better antibody immunotherapies.

In this lesson, students will do a series of activities to explore the role of antibodies in our immune system. They will also investigate how doctors use monoclonal antibodies as part of immunotherapy to treat diseases like cancer.

Prep Work (10 minutes)

Engage (15 minutes)

Explore (60 minutes: Three 20-minute activities)

Reflect (15 minutes)

Assess

Make Career Connections

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