CAR-T Cells, Immunotherapy, and 3D Models in Cancer Research | Immunotherapy | Corning

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Until recently, there were three pillars of cancer treatment: surgery, radiotherapy and chemotherapy. But a fourth pillar has emerged — immunotherapy — and it's powered by innovation.

Chimeric antigen receptor T cells — CAR-T cells, for short — are an innovative development in the field of oncology, contributing to the emergence of immunotherapy as the fourth pillar of cancer treatment, particularly for patients with late-stage or rare forms of cancer. Combined with 3D cell culture models, they are positioned at the forefront of the newest research.

What Are CAR-T Cells?

CAR-T cells are made using a patient's T-cells, which are harvested through apheresis and built up in a laboratory through the addition of a chimeric antigen receptor. When the CAR-T cells return to the patient's body, they target cell-surface antigens expressed on tumor cells.

For patients with B-cell malignancies, CAR-T therapy has shown the possibility of achieving complete remission. However, such treatments haven't had similar success targeting solid tumors. Solid cancerous masses are often hypoxic, acidic, and immunosuppressive, The Scientist writes, and T cells have a hard time surviving in that environment — if they can infiltrate it at all.

CAR-T Cells and Spheroids

3D multicellular tumor spheroids are a type of 3D cell culture models, which have been shown to more accurately mimic in vivo solid tumor biology. Studies have shown that spheroids can show more resistance to chemotherapy than 2D monolayer cell cultures. 3D spheroids develop hypoxic cores and exhibit a diffusion profile for drugs similar to tumors, according to a study of CAR-T cell screening in tumor spheroids.

The study used Corning® Spheroid Microplates — which enable faster, more reliable creation of 3D multicellular tumor spheroids — to quantify the cytotoxic effects of CAR-T cells on tumor cells grown as spheroids. Results showed that the CAR-T cells specifically targeted the tumor cells and induced cytotoxicity. In combination with CAR-T cells and cytotoxicity assays, the microplate provides a high-throughput platform for creating and screening tumor spheroids using CAR-T cell assays.

Challenges of CAR-T Immunotherapy

One challenge in using CAR-T immunotherapy to treat solid tumors is delivering the CAR-T cells directly to the tumor. For blood cancers, The Scientist reports, CAR-T is typically administered via infusion into the blood. But though T cells can cross the blood-brain barrier and reach brain tumors, for example, they don't usually arrive in sufficient numbers to kill the tumor. Researchers are working on ways to get the CAR-T cells to persist longer in the body with repeated infusions; they're also working on ways to administer the cells locally, such as into the intrapleural space for lung cancer.

Selecting the proper antigen target is also key. If researchers don't build a CAR-T treatment that hits only cancer cells and spares the healthy cells around them, there can be serious and dangerous side effects. Testing CAR-T therapy on 3D spheroids can help scientists pick the proper antigen targets. A high-throughput system, like the one utilized in the Corning study, could provide additional insight into antigen targets before the clinical stage.

Future research into 3D immunotherapy is critical, and continued use of spheroids can help to overcome present challenges. Each day brings new innovation and hope — and maybe draws us closer to the day when CAR-T becomes synonymous with cure.