Beyond classifieds for yogurt and fitness supplements, probiotics can revitalize cell-based cancer immunotherapies, such as the CAR T treatment. Remarkably, a paper published in Science demonstrates how those living microorganisms can query overloaded T cells in the environment of a fake tumor, a feat that existing treatment iterations have yet to overcome. Although this approach is still in the experimental phase, it may only be a prospective response to this challenge.
CAR T Therapy for Solid Tumors
At the center of this study is chimeric antigen receptor T-cell therapy, a revolutionary cell-based treatment for certain types of blood cancer, including giant B-cell lymphoma, acute lymphoblastic leukemia, and multiple myeloma, among others. For this therapy, white blood cells called “killer” T cells are extracted from the patient and modified in the lab to generate an artificial receptor. Once the patient receives the rejuvenated cells, the receptor increases the killer T cells’ ability to recognize and eliminate a programmed target. It is known as a “living medicine” because cells multiply in the body and fight cancer.
Treatment with CAR T can cause remission of difficult-to-treat blood cancers, but it fights false tumors despite intense study efforts. Solid tumors present different demanding situations that classic treatment with CAR T cannot yet resolve. Tumors express a wider diversity of biological tags, or antigens, than blood-motile tumors. This makes it more complicated to identify an explicit target for CAR T mobiles. What is needed are tumor-associated antigens (AATs), or antigens that are unique to tumors. and it is not shared across general healthy tissue. Suppose a CAR T mobile is programmed to chase an antigen found in tumors and healthy tissue. In this case, fatal toxicity can occur if the mobile attacks the provided antigen well in healthy tissue. Tumors exhibit antigen-negative relapse due to selective pressures exerted through targeted therapies.
Probiotics and CAR T cells (ProCAR)
In the quest to combat fake tumors, others are demonstrating boundless inventiveness and a relentless commitment to innovation. This is the case of researchers at Columbia University, who have created a formula that dispenses with traditional antigen labels. Instead of relying on antigens to represent CAR T cells, your CAR T cells rely on probiotics, sometimes bacteria found primarily in the gut, to recognize and besiege the tumor. The combination of probiotics and CAR T cells (ProCAR) can achieve the tumor-specific target that traditional strategies lack.
The experimental formula is based on three main components: engineered bacteria, a molecular tag, and CAR T cells. First, a known probiotic strain called Escherichia coli Nissle 1917 (EcN) is introduced into the tumor. Bacteria infiltrate the tumor despite hostile situations and selectively colonize the tumor site. Bacteria are designed to equip an artificial genetic circuit; The circuit triggers lysis events, allowing the bacteria to cyclically release the genetic data needed to produce the molecular tags, but only once the bacteria’s growth in the created tumor environment has reached a critical population density.
The tag is made up of a modified green fluorescent protein and a component that binds to molecules found in greater abundance in most man-made tumors, adding collagens and fibronectins. The CAR T mobile binds to the green fluorescent protein on the tag, activates its signaling domain, and releases cytotoxic immune chemicals to block the counterfeit tumor.
The key to this platform is tumor-restricted bacterial growth. In theory, with the tags located in the center of the tumor, CAR T cells know exactly where to deliver their cytotoxic force.
ProCAR demonstrates evidence of concept
How do probiotic-driven CAR T cells work?The study authors conducted a series of experiments to determine whether their ProCAR platform could safely and effectively target fake tumors.
Immunocompromised mice with cancer were given an intratumoral injection of probiotics generating the desired tag, probiotics generating a green fluorescent protein, or an empty control. CAR T cells were delivered to the tumor 48 hours later. Probiotics that produced green fluorescent protein did not slow tumor expansion; These proteins do not have the binding sites necessary to anchor to the tumor. In contrast, the Tag probiotic particularly slowed tumor expansion and advanced survival without affecting mouse body weight (an indicator of mouse health). They grow larger beyond the tumor’s escape into healthy organs a few days after the initial injection, highlighting the tumor-specific expansion of those bacteria.
Mice with intact immune systems were also tested. Here, the ProCar platform effectively slows the progression of the colorectal tumor and induces an adaptive immune response. The result implies that those ProCAR T mobiles can harness the immune system’s herbal ability to fight cancer. However, this phenomenon appears to be limited to mice and not applicable to human mobile cultures.
CAR T treatment is administered systemically; When the cells are infused, they circulate through the frame to locate their target. Could ProCAR cells still be effective if administered systemically?The authors incorporated some other mechanism into the bacterium to help CAR T cells locate their mark. These probiotics released the molecular tag along with an artificial immune chemical called CXCL16 to directly recruit CAR T cells to the tumor site. Mice with tumors that received a single intravenous injection of CAR T cells showed reduced tumor expansion without decreasing body weight. A comparison showed that the immune system’s release of the chemical CXCL16 complements the healing benefit.
Takeaway Meals
Solid tumors have eluded traditional immunotherapies, but probiotic-powered CAR T mobiles could possibly stand a chance. This study shows that probiotic bacteria can facilitate the activity of CAR T mobiles, allowing precise and effective targeting of false tumor mobiles. Taking this flexible style further, the researchers also illustrate how this antigen-independent platform can be changed to jointly release recruiting immune chemicals. These effects recommend a promising approach to avoid targeting tumor-associated antigens.
It is still known how this experimental combination (probiotics and CAR T treatment) will work in humans. This formula will likely require changes for clinical translation, as humans are more vulnerable to bacterial toxins than mice. Ultimately, this study offers a credible new avenue of research, and it’s worth pursuing all the answers to solve the pressing challenge of falsified tumors.