Cellular immunotherapy is a treatment that enhances a patient’s immune system to combat diseases, especially cancer. This approach involves modifying a person’s immune cells, often through genetic engineering, and reintroducing them into the body. The therapy trains these cells to recognize and attack abnormal cells they previously could not identify.
The Mechanism of Cellular Immunotherapy
The immune system has specialized white blood cells called T-cells that identify and eliminate abnormal cells by recognizing specific markers, known as antigens, on their surface. Since cancer cells can often evade detection, cellular immunotherapy modifies a patient’s T-cells to effectively recognize these cancer-specific antigens. In the lab, these cells are reprogrammed to enhance their targeting ability. The engineered cells are then multiplied into the millions or billions before being returned to the patient to seek out and destroy cancer cells.
Types of Cellular Immunotherapies
One type of cellular immunotherapy is Chimeric Antigen Receptor (CAR) T-cell therapy. This technique genetically engineers a patient’s T-cells to produce synthetic receptors called CARs. These lab-created receptors are designed to recognize a specific antigen on the surface of cancer cells. CAR T-cell therapy has been successful in treating certain blood cancers by enabling the modified T-cells to target and eliminate malignant cells.
Tumor-Infiltrating Lymphocyte (TIL) therapy uses naturally occurring immune cells found within a patient’s tumor. The process involves surgically removing a piece of the tumor and isolating the TILs. Scientists identify the TILs most active against the cancer, multiply them to large numbers, and re-infuse them into the patient. TIL therapy is primarily used for treating solid tumors like melanoma.
A third approach is T-cell Receptor (TCR) therapy, which also genetically modifies a patient’s T-cells. Instead of adding a synthetic receptor, TCR therapy enhances the T-cell’s natural receptor. This modification makes the receptor more efficient at recognizing cancer antigens presented by the major histocompatibility complex (MHC). This allows TCR T-cells to target a broader range of antigens, including those found inside the cancer cell.
The Patient Treatment Process
The treatment process begins with collecting a patient’s immune cells through a procedure called leukapheresis. Blood is drawn, passed through a machine that separates the white blood cells, and the remaining blood is returned to the body.
The collected T-cells are then sent to a laboratory for manufacturing. This phase involves genetic modification and expansion, which can take several weeks. During this time, the patient might receive bridging therapy to control the cancer.
Before the infusion, the patient undergoes conditioning therapy. This short course of chemotherapy reduces existing immune cells, creating a better environment for the new cells to expand.
The final step is the infusion of the engineered cells, which is similar to a blood transfusion. After the infusion, patients are monitored in a hospital for several weeks. This powerful immune activation can cause side effects like Cytokine Release Syndrome (CRS) and neurotoxicity, which require careful medical management.
Conditions Treated with Cellular Immunotherapy
Cellular immunotherapies are approved for treating several cancers, particularly blood cancers. CAR T-cell therapies are established treatments for conditions where the disease has returned or not responded to other treatments, including:
- Non-Hodgkin lymphoma (such as diffuse large B-cell lymphoma and follicular lymphoma)
- Multiple myeloma
- Mantle cell lymphoma
- Acute lymphoblastic leukemia (ALL)
The application of these therapies extends beyond blood malignancies. In early 2024, a TIL therapy was approved by the FDA for treating metastatic melanoma, an advanced skin cancer, marking the first cell therapy approved for a solid tumor.
Research continues to expand the use of cellular immunotherapies for a wider array of conditions. Clinical trials are actively investigating their effectiveness for other solid tumors, such as lung, liver, and brain cancers, with studies aimed at improving safety and efficacy.