Contemporary VCE BiologySequence 1: CAR-T Cell Immunotherapy ⟩ Module 2:
CAR-T cell technology
The second module within Sequence 1 focuses on developing an understanding of the science behind the creation of CAR T-cells, their biology and the process involved in killing cancer (target cells). It is possible that this module could take 1-3 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
Immunity
- the use of monoclonal antibodies in treating cancer
With a focus on:
- the characteristics and roles of T cytotoxic cells, in particular CAR T-cells, in identifying and killing target cells
Duration
1-3 hours
Student learning outcomes
On completion of this module, students will:
- identify the role of cytotoxic T-cells in immunotherapy
- demonstrate a knowledge of the cellular processes involved when cytotoxic T cells attack and kill target cells
- identify the role of the major histocompatibility complex (MHC) in recognition of antigens and activation of T cells
- understand how cytotoxic T-cells have been genetically modified to create CAR-T cells
- identify the various current research, and their role in improving CAR T-cell effectiveness
Teacher background information
Module description
Cytotoxic T cells, also known as cytotoxic T lymphocytes (CTLs) are specialized white blood cells that, when activated, seek out and kill infected cells. The CAR T cells discussed in the previous module are cytotoxic T cells that have been genetically modified to improve the ability to target and kill cancer cells.
In this module, students investigate the structure and actions of a cytotoxic T cells; how they detect and attack cancers cells, also known as target cells. Students engage in a number of concrete and creative activities, including being introduced to appropriate scientific vocabulary, and demonstrating their understanding of the cellular processes involved in T cell mediated killing.
In the second part of the module, students are introduced to investigative research aimed at improving CAR T cell technology. Students observe videos from scientists at the Walter and Eliza Hall Institute (WEHI) who are involved in research to improve the efficacy of CAR T cells.
Additional introductory resources
Article
Design and Development of Therapies using Chimeric Antigen Receptor—Expressing T cells
This article describes the design of CAR expressing T cells, and how they are able to recognise and kill target cells independently of the major histocompatibility complex (MHC), so that target cell recognition is unaffected by some of the major mechanisms by which tumors avoid MHC-restricted T-cell recognition.
Article
Challenges to Chimeric Antigen Receptor (CAR)-T Cell Therapy for Cancer (2014)
A publication that looks at how CAR receptors have evolved in response to challenges in effectively killing target cells. It explores how CAR T cells are able to bypass the MHC-mediated process making them more effective in killing cancer cells.
Video
Immunotherapy: Harnessing Your Body’s Own Defenses to Fight Cancer (6:56)
A video that describes the success of CAR T therapy within the wider scope of immunotherapy. A good video to revisit immunotherapy before investigating T cells and CAR T technology.
Article
T Cells and MHC proteins
An article about the role of MHC I & II in T cell activation and replication.
Teaching sequence
Part 1 Serial killer T cells
1-2 hrs
Student knowledge/ skills outcome:
- identify the role of cytotoxic T-cells in immunotherapy
- demonstrate a knowledge of the cellular processes involved when cytotoxic T cells attack and kill target cells
- identify the role of the major histocompatibility complex (MHC) in recognition of antigens and activation of T cells
Prior Knowledge: Previous module completed
Activities
After reading and watching a number of resources below, students can undertake a range of activities to demonstrate their knowledge of cytotoxic T cell mediated killing of target cells.
Background and resources
Book excerpt
Cellular and Molecular Immunology 8th Edition (NY Times 2012), Chapter 11 Differentiation and Functions of CD8 + Effector T Cells (pp. 231-238), A Abbas, A Litchman & S Pillai (2015, Elservier Inc)
In this chapter, the authors describe how functionally effective cytotoxic T lymphocytes (CTLs) are produced and how they kill target cells. The chapter outlines the process of CTL-mediated killing through antigen recognition, activation of the CTLs, delivery of the lethal hit that kills the target cells, and release of CTLs. It describes each of these steps and how they are controlled by specific molecular interactions. It provides excellent illustrations.
Video
CTL killing a target cell (1:17)
Video microscopy of a cytotoxic T lymphocyte in action. Narration explains the role of granzymes and the process of target cell self-destruction.
Video
Cytotoxic T cell and MHC I complex (9:15)
From 2:25 mins the presenter introduces the concept of cytotoxic T cells and the MHC I complex and the presentation of antigens within an infected cell. It describes how cytotoxic T cells have a variable portion on their receptors that bind to proteins displayed on MHC I complexes and how these activated cytotoxic T cells replicate into memory and effector T cells. It describes how the effector cytotoxic T cell binds to the antigen presented on the target cell, and then releases the enzymes perforin (which create holes in the target cell wall) and granzymes (that induce a target cell to kill itself)
Activity 2.1 - Defining CTL mediated killing
In this activity, students have a list of the terms used in T-cell mediated killing of target cells. Students are required to link various definitions with the correct term. An activity that can be used to verify student’s understanding of the role of various cells and molecules required as part of target cell destruction. The terms and their definitions are contained in pages 1 and 2 of the resource pack (MSWord 370KB).
Activity 2.2 - The process of CTL mediated killing of target cells
In this activity, students are required to cut out a list of the actions involved in CTL mediated killings of target cells, and place them in the order of events occurring. Pages 3 and 4 of the resource pack (MSWord 370KB).
Activity 2.3 - Slowmation of cytotoxic T cell and target cell interaction (group activity)
In this activity, students are asked to create a 2-dimentional slowmation (also known as a stopmotion) animation demonstrating their understanding of how a cytotoxic T cell finds and kills a target cell. This activity promotes student creativity by encouraging the use of everyday items (such as string, beads, sand etc…) for students to construct representations of T cells, target cells, receptors and the various enzymes. Students use appropriate digital technologies outlined in: http://www.digiexplanations.com/slowmation.html.
Students should read Chapter 11 listed in the resources above (p. 231-238) prior to undertaking this activity, as the chapter clearly explains the process and provides good illustrations to support students in building their 2D models (note: The teacher is encouraged to create their own version of a slowmation to model the process).
Part 2 CAR T cell technology
1 hr
Student knowledge/ skills outcome:
- understand how cytotoxic T-cells have been genetically modified to create CAR-T cells
- identify the various current research, and their role in improving CAR T-cell effectiveness
Prior Knowledge: Previous module completed
Activities
Background and resources
Student handout
T cell receptors (TCR) and chimeric antigen receptors (CAR)
Pages 5-8 of the resource pack (MSWord 370KB). A brief illustrative and informative outline of the differences between TCR and CAR receptor actions and technology.
Activity 2.4 - Similarities and differences between TCR and CAR receptors
Students watch the video and read the hand out. Students create a Venn diagram to identify the similarities and differences in appearance and actions in CAR T cells and effector T cells. Students share their Venn diagrams in small groups, generating collaborative discussions. The class comes together to create a whole-class Venn diagram, where the teacher can scaffold and guide the discussions.
Activity 2.5 - Creating a CAR T-cell
Students use any medium (cut and paste/ animation/ annotated diagram etc) to genetically modify their own T-cell to create a CAR T-cell. Students identify components of the CAR T-cell that are used to kill target cells. A way to look at the similarities and differences of individual components of a TCR and 3rd generation CAR.
Activity 2.6 - Draw your own CAR T-cell
Similar to activity 2.5, students demonstrate an understanding of T cell receptor technology by creating their own illustrations of T-cells and CAR T-cells highlighting and explaining how the genetic modifications make a CAR T-cell more effective in attaching to target cells.
Part 3 Improving the effectiveness of T-cell technologies
In Part 2, students looked at how chimeric antigen receptors had evolved over three generations resulting in improved connections and signaling. This section introduces a range of recent and current research being undertaken at the Walter and Eliza Hall Institute (WEHI) in relation to improving T cell effectiveness.
1 hr
Student knowledge/ skills outcome:
- identify the various current research, and their role in improving T-cell TCR and CAR receptor effectiveness
Activities
Background and resources
The following activities are based on students viewing the range of videos:
Activity 2.7 - Visualising the research
In this activity, students can individually (or in small groups) watch each video and complete a visual organizer using prompt questions outlined in the table (Page 9 of the resource pack (MSWord 370KB).)
The questions focus on the research:
- outline (purpose and hypothesis)
- predictions and findings
- implications
Activity 2.8 - Jigsaw strategyl
In an adaptation of activity 2.7, students use a jigsaw strategy to evaluate and describe the T cell research.
The Jigsaw teaching strategy is an effective method for students to learn large amounts of content in a self-directed way. Students are put into groups of four. One representative from each group will watch one of the above videos, working together to analyse and summarise the information using the visual organizer table outlined in page 9 of the resource pack (MSWord 370KB).
They then return to their groups, where they will share the information with their group, teaching the other three students about what they have learnt.
Activity 2.9 - How is research into lymphocyte cell biology improving T cell therapy?
In this teacher-led activity, students create a whole-class mind map to describe the research and how it is improving T cell therapy. The class adds to the mind map after each video.
Next module: Adaptive Immune Responses
