Sequence 1: CAR-T Cell Immunotherapy Module 1:

What is Immunotherapy?

The first module within Sequence 1 focuses on introducing the concept of immunotherapy as a fourth pillar in cancer treatment. It introduces the role of cytotoxic T cells in fighting cancer. It is recommended that this module take between 1 – 2 hours of class time.

Summary

VCE Biology (2017-2021)

Unit 3, Area of Study 2, Outcome 2, VCE Biology Study Design

Key knowledge

Responding to antigens

  • the characteristics and roles of components of the adaptive (specific) immune response including the actions of B lymphocytes and their antibodies (including antibody structure) in humoral immunity, and the actions of T helper and T cytotoxic cells in cell-mediated immunity

With a focus on:

  • the characteristics and roles of T cytotoxic cells in cell-mediated immunity as part of cancer immunotherapy

Duration

1 hour (1 lesson)

Student learning outcomes

On completion of this module, students will:

  • identify that immunotherapy is the use of a person’s immune system to fight disease
  • understand the potential for immunotherapy in treating cancer
  • understand the process of adoptive T-cell therapy
  • be able to describe an overview of the processes involved in CAR-T therapy

Teacher background information

Module description

This section introduces immunotherapy as a fourth pillar of treatment for cancer. Immunotherapy uses a patient’s own immune responses to fight cancer. The use of immunotherapy to treat cancer has been evolving rapidly over the last couple of decades.

Adoptive T-cell therapy (ACT), employing a patient’s own cultured T cells, is an emerging treatment of a variety of cancers. In ACT, the patient's T-cells are removed in a process known as apheresis. The T-cells known to fight the particular cancer in the patient are grown in a laboratory and inserted back into the patient’s body. Recently there has been the evolution of CAR T-cells. CAR stands for chimeric antigen receptors, which is a type of antigen-targeted receptor that has been genetically engineered onto a patient’s own T-cell. The use of genetic engineering approaches to insert antigen-targeted receptors of defined specificity into T cells has greatly enhanced the potential capabilities of ACT. These CAR T-cells are better able to seek out and kill specific target cells (Magee 2014).

The module starts with the use of a hook, to engage and motivate learners to want to understand how T-cell therapies work in the treatment of cancer. The hook is a video about Emily Whitehead, the first child with acute lymphoblastic leukemia (ALL) to be treated with CAR T-cell therapy, with amazing results.

Additional introductory resources

Video

Immunotherapy Harnesses the immune system to fight cancer (3:45)

Published in August 2016, this Fox News video uses medical researchers to describe the concept of immunotherapy, highlighting recent results in immunotherapy treatments. A good introductory video.

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Website

Leukemia & Lymphoma Society: Chimeric Antigen Receptor (CAR) T-cell Therapy

This website provides a basic overview of the cyclic process of adoptive T-cell therapy in cancer patients. It presents an easy to follow flow diagram on the processes involved in harnessing T-cells from patients and genetically inserting Chimeric Antigen Receptors (CAR) to create CAR T-cells that are then replicated and administered back to the patient.

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Video

What is immunotherapy? (3 mins)

This video gives a brief and concise outline of immunotherapy. It raises the concept of ‘self’ and identifies cancer as ‘self’ gone bad. The video highlights the challenges of immunotherapy such as the balance of stimulating the immune system to fight cancer without attacking the rest of the body, and the idea of using immunotherapy to maintain immunity against cancer. It is a good video if students require additional scaffolding information about immunotherapy in general.

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Article

6 questions in cancer immunotherapy) (Hutch News 2016)

Stories of seemingly miraculous outcomes are coming from a growing field of cancer treatment called immunotherapy, a broad term that covers a range of treatments that harness patients’ immune systems to fight cancer. This article looks at a number of questions in relation to the effectiveness of immunotherapy.

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Website

Cancer Australia: What is immunotherapy?

Australian Government website that outlines the different ways, other than CAR T-cell therapy, that immunotherapy can be administered. Provides information on alternative treatment options that are also considered immunotherapies.

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Article

Immunotherapy the new tool in cancer fight (ABC 2014)

A basic overview of immunotherapy.

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Article

The difference between passive and active immunotherapy and their impact on cancer treatment (Science Nutshell 2015)

An overview of the different types of immunotherapy.

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The differences between effector Tc cells and CAR T-cells
Improving the 'strength' of the synaptic connection between the receptor and tumour antigen
Perforin release by cytotoxic lymphocytes
CAR vs.TCR: Is one more effective than the other in serial killing capabilities?
Where to from here?

Teaching sequence

Part 1 Introducing immunotherapy: The story of Emily Whitehead

The activity is designed to introduce immunotherapy, in particular CAR T-cell therapy through the story of Emily Whitehead, the first child to undergo a successful clinical trial using CAR T-cell therapy for the treatment of leukemia.

20-40 mins

Student knowledge/ skills outcome:

Prior Knowledge: Nil

Activities

Background and resources

At the age of 5, Emily was diagnosed with a type of blood cancer called acute lymphoblastic leukemia or ALL. Although this is currently the most treatable leukemia in children, with around 90% cure rates, Emily relapsed after 16 months of chemotherapy with a highly resistant disease and was given just a few weeks/months to live. She was then enrolled on a clinical trial at the Children’s Hospital of Pennsylvania. She was the first child to be given T cells genetically reprogrammed to recognize cancer cells, which were developed at the University of Pennsylvania. Emily is still in remission and is leading a happy and healthy life (Cancer Immunology and Immunotherapy Centre, University of Birmingham 2016).

Video

Emily's Story: A Young Girl Beats Cancer with Immunotherapy (5:35)

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Video

Emily Whitehead First Child Treated in Trial of T Cell Therapy for Acute Lymphoblastic Leukemia (6:44)

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Article

A Girl’s Last Hope, Altered Immune Cells Beat Leukemia (NY Times 2012)

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Other relevant Articles
Article

An Immune System Trained to Kill Cancers (NY Times 2011)

An article that highlights another cancer survivor’s fight, and elaborates on the benefits and side effects of T-cell therapy. It provides a greater depth of information, highlighting the notion that T-cells ‘search’ for cancer cells, and introduces the concept of antigens and receptors (in particular the protein CD 19 which is found on all B-cells, including cancerous B-cells).

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Activity 1.1 - What is Immunotherapy?

Teachers can choose to use one or all of the following activities: a mind map, think-pair-share, and listing pros and cons.

Whole class mind map

Create a whole-class mind map about students' understanding of immunotherapy within the scope of the case study of Emily Whitehead. Suggested mind map headings could be, but are not limited to: Immunotherapy, CAR T-cells, Cancer, Clinical Trials. Place the mind map on the classroom wall for the duration of the unit.

Think-pair-share

Students undertake a collaborative activity to answer the question(s): What is immunotherapy? What is CAR T-cell therapy? Students think individually about the question(s), undertake independent research and then share ideas with a classmate. This activity could be used for students who have difficulty in sharing within a whole-class forum.

Pros and Cons

Students list the pros and cons of using CAR T-cell therapy. This list can be generated by the individual or from group discussion. Use additional supporting information, such as the article ‘6 questions in immunotherapy’ to scaffold discussions.

Part 2 What is Adoptive T-cell therapy?

Adoptive T cell therapy for cancer is a form of transfusion therapy consisting of the infusion of various mature T cells with the goal of eliminating a tumor and preventing its recurrence. This activity is designed to build from the previous case study, identifying the key steps in adoptive T-cell therapy. Students will watch a range of videos and read a number of articles and then (either individually or in groups) visualize the process of Adoptive T-cell therapy through a range of strategies.

20 - 40 mins

Student knowledge/ skills outcome:

Activities

Background and resources
Video

Adoptive Cell Therapy: Turning Immune Cells into Cancer Fighters (2 mins)

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Blog

Adoptive T Cell therapy: Harnessing the immune system to fight cancer

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Activity 1.2 - Visualising Adoptive T-cell therapy

Students use a range of visual strategies to represent their understanding of the key processes of apheresis, screening, replicating and re-introducing T-cells to the patient. Visual representation can be in the form of, but not limited to a:

  1. Flow diagram
  2. Mind map
  3. Concept map
  4. Illustration
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Contributors

Thanks to the following for contributing to the development of these sequences:

Special thanks to Ian Bentley and Mary Vamvakas