Intercellular Star Wars: Force Shields, Checkpoints, Light Saber, Death Star and the Immune Cells

By: Alex Y. Huang, MD, Ph.D.

This weekend, millions will flock to movie theaters to watch the latest installment of a 40-year long unfolding drama taking place a long time ago in a galaxy far, far away. “Rogue One: A Star Wars Story” promises to reveal hidden secrets behind how the resistance stole the plans to the Death Star. As with the previous seven films, “Rogue One” will speak of the struggle between good and evil, the reliance on teamwork for success and the importance of making the right choices under difficult circumstances.

In anticipation for this movie, I couldn’t help but think of how Star Wars, and the battles fought in each episode, resembled the battles being fought in the field of pediatric cancer research. A similar story is being told in the hallways of children’s hospital oncology floors, at the benches of research laboratories and across many university campuses and pharmaceutical companies — a story which is more similar to Star Wars than even George Lucas could have imagined.

For pediatric, adolescent and young adult (AYA) cancer patients and their families, a rebellion against the dark and powerful Empire, cancer, has begun. Fans of Star Wars would recall that Anakin Skywalker was the chosen one, believed to bring balance to the force as a Jedi. However, during his training, Anakin turned to the Dark Side and became Darth Vader, with his ambition to take over the Galactic Empire — similar to what happens in the body when cancer cells begin to go “rogue”.

Many tumor cells multiply quickly, much like the Storm Troopers, overwhelming fighters by sheer numbers. Some tumor stem cells are more advanced than the Storm Troopers. Though few in number, they are highly resistant to any assault and possess the power to cause menace — they are much like Darth Vader and the other Sith Lords. The cancer cells themselves are also similar to the Death Star, an impenetrable killing machine. They form tumors with defense shields around them, which resist attempts to destroy them by chemotherapy, radiation and the body’s immune system.

Just like we learned in the Star Wars movies, the Death Star is not completely impenetrable; and childhood cancer researchers have learned that cancer cells are not totally impenetrable either. Researchers are discovering new ways to target and kill cancer cells. 
 
 The first indication of the demise of the Death Star was finding its architectural blueprint. This secret information revealed to the Rebel Forces the vulnerabilities of the Death Star so that Luke Skywalker was able to destroy the giant floating fortress with just one shot. In a similar way, advances in research and the development of precision medicines are now revealing hidden secrets of tumor cells and making them vulnerable to attack.

An even more remarkable story in the fight against pediatric and AYA cancers is the emergence of immunotherapy. Engineered Chimeric Antigen Receptor (CAR) T cells resemble the highly trained and skilled Jedi, who can slash their way through enemy lines with flaring Light Sabers. As no two Jedi are exactly alike, each T cell in the body is different from one another. CAR T cell therapy puts the homing beacon and Light Saber in the same weapon, allowing these T cell Jedi to search and destroy the enemy Storm Trooper tumor cells.

As a mighty opponent, the Galactic Empire does not accept the Rebel and Jedi’s attack without a fight. A commonly employed technology by the Empire to resist Rebel attack is the use of the Force Shield. As you recall, it’s the teamwork by the Ewoks that helped to destroy the Force Shield generators that allowed a vulnerable Death Star to be destroyed by shots fired from the Millennium Falcon in Episode VI.

Well, researchers have now found some of the Force Shields protecting tumor cells. These Force Shields, called immune checkpoints, can be potently disabled by checkpoint inhibitors thereby allowing the immune cells to effectively target and kill tumor cells. This blockade approach has been highly successful in many resistant and refractory cancers in adults, and we eagerly await results from ongoing pediatric clinical trials utilizing these agents.

Fighting the Galactic Empire takes a lot of resources by the Rebels and Jedi. The same is true for childhood and AYA cancer research funding — many incredible volunteers and donors give to organizations like St. Baldrick’s Foundation. These groups fund cutting-edge research to try and stop the cancer Death Stars attacking kids today. Through childhood cancer research, we are now witnessing the “New Hope” in the form of new treatment options against the “Attack of the Clones” by the “Phantom Menace” — the heinous cancers that continue to attack kids. The cancer Rebel forces and Jedi have emerged, the “Force” has been awakened — and they are not going to stop fighting!

So, as you grab your popcorn and join millions this weekend to indulge in the saga of Star Wars, be equally excited about the “Childhood Cancer Cell Wars” that are raging across this land that hold great promise to bring total victory to the fight against childhood and AYA cancers. 
 
 Indeed, the Force has been awakened; a new hope is on the horizon. 
 
 Hold on to your seats to find out who or what, in the annals of childhood and AYA cancer therapy discovery, will be the “Rogue One(s)” to bring total destruction to the evil cancer Empire!

This article is dedicated to Kelly Kinney, a courageous fighter who stood up to the Osteosarcoma Empire. She was working on a Star Wars analogy to Childhood Immunotherapy when she passed away after a Galactic battle with cancer.

Kelly shaving Dr. Huang’s head at a St. Baldrick’s event.

Alex Y. Huang, MD, Ph.D. is Associate Professor of Pediatrics at Case Western Reserve University and the Angie Fowler AYA Cancer Institute / UH Rainbow Babies & Children’s Hospital. He is also a St. Baldrick’s Foundation research grant recipient and aspires to be Yoda.