Immune-Image explores a new strategy for imaging CAR-T Cells

CAR-T cells, or chimeric antigen receptor T cells, are a type of immunotherapy that has shown great success in treating a subset of blood cancers. In this therapy, the patient’s own cells are genetically modified to recognize and target specific proteins on cancer cells. However, CAR-T cell therapy has had limited success so far in the treatment of solid tumours (cancers that are not in the blood). The Immune-Image project is exploring a new strategy for imaging CAR-T cells with multiple imaging modalities to better understand their behaviour in the body and therefore facilitate the application of CAR-T cell therapy to fight solid tumours.

The basic idea behind CAR-T cells is to use the body’s own immune system to fight cancer. To do this, researchers take T cells, a type of white blood cell that plays a key role in the immune system, from a patient’s blood. They then modify the cells in the lab to produce chimeric antigen receptors on the T cell surface. These receptors are designed to recognize and bind to specific proteins on the surface of cancer cells. Once the CAR-T cells are introduced back into the patient’s body, they can find, attack and effectively kill cancer cells in the blood (blood cancers), but struggle to infiltrate into solid tumour masses (solid cancers). To elucidate why this happens and how the efficacy of CAR-T cell therapy in solid cancers can be improved, a new imaging tool to track CAR-T cells is needed. This is where the Immune-Image project comes in.

New method of imaging CAR-T cell migration into solid tumours

Researchers at Cambridge University have developed a way of imaging CAR-T cells using near infrared (NIR) fluorescence imaging and Magnetic Resonance Imaging (MRI). In addition to modifying T cells to produce chimeric antigen receptors on their surface, cells are additionally modified to produce channels in their membrane that allow uptake of certain contrast agents into the cells, making them imageable. The channel is called Organic Anion Transporting Polypeptide (OATP) and if cells have it, they can reversibly take up the clinically approved contrast agents Indocyanine Green (a fluorescent contrast agent) and Primovist (a gadolinium-based MRI contrast agent), allowing cell tracking with near-infrared fluorescence imaging and MRI, respectively. Combining these two imaging modalities takes advantage of both the sensitivity and low background of NIR fluorescence imaging as well as the excellent soft tissue contrast generated in MRI. This method will therefore allow researchers to better understand how the cells interact with cancer cells and the surrounding tissue, identify any potential issues that may arise during treatment and use the knowledge gained to extend the use of CAR-T cell therapy to solid cancers.

Goals and key benefits

The ultimate goal of this imaging strategy is to know if and where CAR-T cells accumulate in the body and how well they survive there, which in turn might elucidate new mechanisms, allowing CAR-T cell therapy to be extended to tackle solid cancers instead of only subsets of blood cancer. One of the key benefits of combining CAR-T cell therapy with multiple clinical imaging techniques is the ability to personalize treatment for each patient. By tracking the behavior of CAR-T cells in real-time, doctors could adjust treatment plans as needed, ensuring the best possible outcome for each individual patient.

Overall, the Immune-Image project represents an exciting step forward in cancer treatment. By using a combination of cutting-edge immunotherapy and imaging techniques, researchers are able to gain a better understanding of how cancer cells interact with the body’s immune system, and develop more effective personalized treatments for patients.

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