CAR-T Cells: Engineered Cancer Killers


© Maja Divjak, PhD, Grad Cert 3D Animation (AFTRS)

Maja Divjak’s CAR-T Cells: Engineered Cancer Killers won the Premier Award and Medical Education Award in the Interactive Learning and Website Division in BioImages 2022.

What was your concept when creating this animation? Was it for a job or for personal creativity?

I work as a Biomedical Animator at the Peter MacCallum Cancer Centre in Melbourne, Australia. Based on 25 years of research, Peter Mac is the first site in Australia fully licensed to manufacture Chimeric Antigen Receptor (CAR)-T cells for treatment of blood cancers such as leukaemias and lymphomas. The process involves engineering a patient’s own immune T cells to express Chimeric Antigen Receptors, or CARs on the cell surface. When the CAR-T cells are reinfused into the patient, they multiply rapidly and the CARs enable them to specifically seek and destroy cancer cells throughout the body. For some patients this has proven to be a miracle treatment when all other options have failed.

We recognised a need to explain these complex processes in detail, so I created a 3D animated production illustrating how CAR-T technology works at the molecular level, highlighting the elegance of the CAR structures and also the complexity of our inner cellular world, which most of us are completely unaware of. The production is designed to educate patients and the interested lay person about this unique technology for treatment of cancer and to inspire confidence in cancer patients considering this therapy.

Tell us something about the creative process you use when coming up with a solution to a problem/assignment.

I start with a lot of reading and a literature review to ensure I understand the science behind the story, then I distil that review into a visual format or storyboard, which is like a comic strip outlining all the shots in sequence. I then write a script, which is very useful for controlling the flow and timing of the animation, as the length of each shot is defined by what needs to be said to explain each shot. The script will change a lot as the animation progresses and evolves.

Working with 3D animation software called Autodesk Maya, you will then assemble your molecular models from structures sourced from the protein databank or PDB. Typically, you will only find fragments of structures in the PDB, not whole molecular assemblies, so this process involves a lot of sleuthing to complete the structural puzzle. You then have to rig your molecular assemblies, which is somewhat like creating a digital scaffold to keep the fragments together and then you can animate the molecular structures by applying physical forces to the scaffold. Throughout the modelling and animation process, you will add pretty colours and textures to the structures and you will light the scene and add cameras and camera movement to direct the viewer’s gaze and facilitate understanding.

Rendering is the process whereby each frame of the shot is built pixel by pixel by the computer. Each second of animation consists of 25 frames and in my case, each frame is 1920 x1080 pixels, which is a lot of pixels your computer has to generate. As you can imagine, this can be a real bottleneck in the process, depending on the complexity of your scene. The rendered frames are then put in order in Adobe After Effects in a process known as compositing. I will also edit, add special effects, labels and captions at this time. Finally, I work with voiceover artist Dr Clare Fedele to record the narration and sound effects are created by Ryan Granger and the wonderful team at Dead on Sound. The sound effects really bring the production to life and are integral to the production, not an afterthought. The final movie output is done using Adobe Premiere. As you can see, the pipeline for creating an animated production is a long one. Phew!

What technical issues did you have, or have to work out, to create this animation?

As described above, many of the molecules illustrated in this production have been painstakingly constructed from X-ray crystallography data in the PDB, reflecting the scientific knowledge as it currently stands. However, for construction of the CARs, no structural data were available. So, CARs had to be constructed piece by piece, by inferring the protein sequences from published DNA primer sequences (Milone, MC et al, Mol Ther Vol 17, no. 8: P1453-1464. 2009) and then searching for protein matches using the National Library of Medicine Basic Local Alignment Search Tool (BLAST). This is the first time to my knowledge that CARs have been constructed and animated at the molecular level. It is also noteworthy that where possible, I have constructed and animated the majority of molecules at atomic resolution, the finest level of detail possible.

Tell us something about the subject of this animation.

This 3D animated production was created to show how CAR-T technology supercharges a patient's own immune cells to combat the processes cancer cells use to hide from our immune system. This revolutionary treatment is now offered to some blood cancer patients at the Peter MacCallum Cancer Centre, so we recognised a need for detailed explanation. To date, only simple, conceptual animations explaining CAR-T therapy are available, which in our opinion fail to highlight the technology as a ground-breaking re-engineering of human immune structures, which seek and destroy cancer cells. Our production shows how CAR-T cells function at the molecular level and explains the process of manufacturing CAR-T cells at Peter Mac.

The process involves extracting immune T cells from the patient and engineering them in the laboratory to express CARs on the cell surface. The CARs enable the cells to specifically seek and bind to cancer cells and then destroy them, without adversely affecting normal cells. Once the CAR-T cells are manufactured, they are reinfused into the patient where they go to work to destroy cancer cells. CAR-T cells can remain in the body for many years and can reactivate if the cancer returns. Also included is trailblazing time-lapse microscopy footage of live immune cells and CAR-T cells in action in the laboratory. These unique sequences provide a window into the living human immune system, showing how CAR-T cells kill cancer cells in a very specific, aggressive way.

What elements are important to you when you judge or critique your work or the work of other professionals?

Scientific accuracy is my number one criterion. The facts of the story must be scientifically accurate, based on the current published literature and the molecular structures represented must also be as accurate as possible. That said, our productions are primarily designed for a general audience and to that end, we don’t use technical language or scientific jargon. They are intended to have universal appeal, for everyone from the highly trained scientist to the interested layperson. Similarly, the productions must also engage on a purely aesthetic level; even if the viewer doesn’t connect with the science, the visuals must be beautiful. Fortunately, the cellular and molecular worlds are visually stunning, so this makes my job easier!

In a nutshell, I look for scientific rigour in my work and the work of others, but also accessibility, to both the scientific concepts and the beauty and complexity of the cellular and molecular worlds, which most of us are completely unaware of.

What is your imaging background?

After completing my PhD in molecular biology at Monash University, Melbourne, Australia, I spent quite some years in scientific sales, but was keen to bring together my love of art and science in some shape or form. A chance meeting with world-renowned Biomedical Animator Dr Drew Berry, at the Walter and Eliza Hall Institute of Medical Research, opened the doors to the wonderful world of science animation. This was a moment of epiphany for me and I knew that Biomedical Animation was what I wanted to do. I then pursued my dream of becoming a Biomedical Animator, studying Multimedia at Swinburne and 3D animation at the Australian Film Television and Radio School.

I was then offered a coveted fellowship with Dr Berry at the Walter and Eliza Hall Institute. The fellowship was part of the VizbiPlus project, which aimed to train three fledgling animators to communicate cutting edge research at their host institutions, using visually captivating 3D animation. Following this I became resident Science Animator at the Gene Technology Access Centre before joining the Peter MacCallum Cancer Centre as the inaugural BiomedicalAnimator.

Who are some of your favourite image makers?

Some of my favourite science and medical animators include the team at Phospho, Mad Microbe, AXS and Hybrid. Prof. David Goodsell is a computational biologist who paints stunning watercolours of the chaotic world inside the cell and cell membrane and is someone whose work truly inhabits the nexus of art and science.

In terms of fine art, I love the introspective, domestic worlds of Vermeer and the decorative opulence of Gustav Klimt.

What images or image makers inspire or influence you?

I have been incredibly lucky to train under Dr Drew Berry, so he has been instrumental in bringing my attention to the world of Biomedical Animation and my development as an animator. I also trained alongside Dr Kate Patterson of Medipics and Prose and I particularly admire the meditative gravitas of her work. The interactive work of the 3D Visualisation and Aesthetics Laboratory at UNSW is also innovative and challenges traditional approaches to science education. The team at Clarafi have also been instrumental in my animation journey, creating a stable of fantastic molecular animation plugins for Autodesk Maya software and being so generous with their technical support.

I count myself lucky to have people in my life who are fine artists. I’m really inspired by the enigmatic photography of Jane Burton, the surrealist paintings of Heidi Yardley, the mythic ceramics of Tiffany Titshall and Belinda Michael and the visceral, expressionist paintings of LB Zaftig.

I’m obsessed with vintage fashion from the 50s, 60s and 70s and Art Deco and mid-century furniture and design. I collect 60s beauty cases and vintage Glomesh and Oroton chainmail designs.

Do you have any advice for people interested in an imaging career in biomedical/life sciences?

If you’re interested in Biomedical Animation, take a good look at the Clarafi website, there are some fantastic Maya tutorials, resources, an animation showcase and a really useful careers page where people discuss how they got into the industry. You will also find the Molecular Maya plugins that have changed my life. If you’re not keen on experiencing the steep learning curve with Maya software, then Blender is another option that is becoming increasingly popular with science animators. Take a look at Brady Johnston’s YouTube for a series of ground breaking Blender tutorials. Then try animating a research area that is really familiar to you, for example, if you did a Masters or PhD, try animating that story. This was a fantastic piece of advice Drew gave me when I was first starting out. It really helps to first animate something you know like the back of your hand and you will learn a great deal. Try collating your work into a portfolio to show to a potential employer or gain access to further formal training. Show your work to professionals you admire and ask their opinion. Also ask their advice on how to enter the field and how they got their break.

Are you a member of BCA and if so how has your membership in the BCA helped you?

Yes, I’m a proud member of the BCA. I find it inspiring that the BCA is comprised of an amazing variety of artists, all with the common goal of engaging people with science and nature and showcasing the beauty of those worlds. I feel I can learn so much from the practice of other BCA members that I can apply to my own work, even though their approach is radically different than mine. The BCA has really opened my eyes to the breadth and depth of biological visualisation.