Great review article published in the JCO here by Daniel Olson et al. summarizing adoptive cellular therapy for solid tumors and where we are today. I am very excited about solid tumor cellular therapy as we are currently enrolling into solid tumor trials specifically for TIL, PD1 knockout TIL, Neoantigen Selective TIL and TCR MAGE4+ T cells at the Orlando Health Cancer Institute.
Imagine your body’s immune system as an elite army, highly trained and equipped to protect your body from intruders. Unfortunately, when cancer enters the picture, it’s like a spy that has learned to blend in with the crowd, effectively evading the body’s defenses. But what if we could give our immune system the secret decoder ring to identify and fight off these disguised enemies? That’s where adoptive cell therapy (ACT) comes into play.
ACT is a type of treatment that amplifies the natural defenses of your immune system. The process involves isolating, growing, and possibly even genetically engineering a patient’s own immune cells from the tumor, specifically T cells (TILs) or peripheral mononuclear cells (PBMCs), to better recognize and fight cancer. Picture it as a top-notch training regimen to turn your T cells, the soldiers of your immune system, into specialized spy catchers.
There are three main kinds of ACT – tumor-infiltrating lymphocytes (TIL), T cell receptor (TCR) T cells, and chimeric antigen receptor (CAR) T cell therapies. Imagine these as the infantry, the special forces, and the super spies of your immune army.
TILs are gathered directly from the patient’s tumor. Like a local guide familiar with the enemy territory, these cells have already been in contact with the cancer and are ready for a fight. They can be expanded rapidly to billions of cells and reintroduced to the patient’s body while giving other supportive drugs that help augment or remove barriers of the immune response. While TILs have shown promise, there is a risk they might expand nonspecific or bystander T cells, akin to training rookie soldiers who may not recognize the enemy very well.
TCR T cells and CAR T cells, on the other hand, are like elite commandos. Through genetic engineering, these T cells are equipped with special receptors that match specific cancer antigens, like giving them a most-wanted poster of the enemy. A key difference between these two is that TCR T cells require a specific genetic match specifically HLA genotype match, much like a key fitting a lock. CAR T cells have no such restriction, giving them broader applicability to the general population.
While ACT has shown encouraging results, there are some challenges. The most notable ones are the potential side effects, which can include severe, even life-threatening, damage to normal tissues and organs. This is similar to the potential fallout from a high-intensity spy operation – there could be unintended collateral damage. TILs are relatively well tolerated and adverse effects are primarily due to the other supportive drugs that are given resulting in potential risk for infection or need for transfusions. TCR or CAR T cell treatments can result in significant potentially life threatening toxicities such as direct organ damage, cytokine release syndrome or severe neurologic syndromes.
Another exciting development in the field is the use of Natural Killer (NK) cells. NK cells act like a rapid response force, reacting quickly to the presence of cancer cells. They can be activated when combined with specific antibodies and require less modification than T cells. In other words, they’re a quicker, more readily available force in the battle against cancer. More trials are ongoing using this new and exciting approach.
Adoptive cell therapy has already shown promise in the treatment of certain blood cancers and has shown signs of effectiveness in solid tumors like melanoma, lung, cervical, and synovial sarcomas. Clinical trials are currently underway to further explore and develop these exciting cellular therapies.
This cutting-edge approach to cancer treatment illustrates the amazing potential of harnessing our body’s own defenses in the fight against this disease. The future of cancer treatment could well be your own immune system, armed and ready for battle.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.
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