6/12/23
Today marks big progress for CAR T-cell therapy. Short for Chimeric Antigen Receptor T-cell therapy, CAR T-cell therapy is used to treat blood cancers. It is able to do so by targeting special white blood cells, known as T-cells, in cancer patients and genetically modifying them via CRISPR.
CRISPR is capable of accomplishing two very important things. First, it is used to knock out the receptors of the T-cell in order to replace them with highly specialized receptors. These new receptors, known as “CARs”, are specific to the cancerous blood cells invading each patient and target the antigens present on their exteriors. If these special CARs act as a highly secure lock, the antigens on the cancerous blood cells act as the sole key. When a CAR T-cell is “unlocked” by these antigens, it triggers an immune response that allows the patient’s body to destroy cancerous cells on its own. Second, CRISPR can remove genes that might interfere with treatment, like the gene responsible for creating PD-1 proteins in white blood cells. When PD-1 is activated in T-cells, it prevents them from killing invader cells within the body. Thus, keeping this protein in CAR T-cells would interfere with their ability to kill cancer cells. And although there is no way to inactivate CAR T-cells, that is part of what makes them such a powerful treatment. They remain in the patient’s body, replicating and fighting cancer all on their own.
In spite of how successful this therapy has been for those with blood cancers, one huge limitation of CAR T-cell therapy has been its inability to target solid tumors. This can largely be attributed to the heterogeneity of tumors. Unlike cancerous blood cells, whose antigens remain rather uniform and accessible from patient to patient, tumor antigens can be sparse, inaccessible, similar to antigens in healthy tissues, or vary immensely. These attributes have made it difficult to design a CAR capable of destroying cancerous tumors. That is, until now.
On June 8, a paper was published by researchers from MIT’s Koch Institute For Integrative Cancer Research announcing that they have successfully found a way to combat any tumor with CAR T-cell therapy. The secret is using amphile fluorescein isothiocyanate tagging, or amph-FITC tagging. Amphs, short for amphiphilic polyethylene glycol lipids (amph-ligands), have the ability to “insert their lipid tails into the plasma membrane of cells in vitro and in vivo without toxicity.” For this study, researchers directly injected human xenograft tumors present on mice with these amph-FITC tags and then treated them with FITC-specific CAR T-cells.
Researchers found that amph-FITC successfully tagged tumors for destruction by FITC-specific CAR T-cells. It was found that 24 hours after one dose was injected, amph-FITC was able to tag around 40-60% of cancerous cells. More than that, amph-FITC was able to target this large percent of cancerous tissue with very little uptake by non-cancerous tissues. This treatment was also found to prevent recurrence via endogenous T-cell memory. When researchers injected control mice (those that received no FITC CAR T treatment) and mice previously cured by FITC/CAR T treatment, the control mice developed tumors while their previously cured counterparts stunted tumor growth despite never being injected with more FITC. This means that on top of precisely being able to destroy tumors, FITC-specific CART treatment can also prevent recurrences of cancer.
While this method has yet to be tested on humans, FITC-specific/CAR T-cell therapy has the potential to treat and cure millions of individuals that battle one of the leading causes of death globally. In the next few years, hopefully researchers will be able to move this testing into a clinical setting where it has the potential to save thousands of lives.