Adoptive cell therapy (ACT) is a modern medical approach that uses a patient’s own immune cells to fight diseases, primarily cancer. This immunotherapy is often called a “living drug” because it modifies and expands the body’s natural defenses. ACT harnesses the immune system’s power to identify and eliminate harmful cells, empowering the patient’s own biology to mount a targeted attack.
The Therapeutic Process
The therapeutic process begins with collecting a patient’s immune cells. This initial step, leukapheresis, involves drawing blood. A specialized machine separates white blood cells, including T cells, from other blood components, returning the rest to the patient.
After collection, isolated T cells go to a specialized laboratory for modification and expansion. There, cells are genetically engineered to express new receptors that recognize specific markers on disease cells, like cancer cells. These modified cells are then multiplied extensively to ensure a sufficient quantity for therapeutic effect.
Before re-infusion, a preparatory step involves chemotherapy. This pre-treatment, called lymphodepletion, reduces existing immune cells in the patient’s body. This “space” allows the newly infused cells to engraft and expand more effectively, enhancing their ability to target the disease.
The final stage involves infusing the prepared cells back into the patient, similar to a blood transfusion. These re-infused cells circulate throughout the body, seeking and destroying target disease cells. The entire process, from collection to re-infusion, can take several weeks, with close patient monitoring.
Major Types of Adoptive Cell Therapy
Chimeric Antigen Receptor (CAR) T-cell therapy is a major form of adoptive cell therapy, particularly for blood cancers. This method genetically engineers a patient’s T cells to produce a synthetic receptor called a Chimeric Antigen Receptor (CAR). This CAR enables T cells to directly recognize specific proteins, or antigens, on the surface of cancer cells, such as CD19 or BCMA, without needing another immune cell to “present” the target.
Once infused, CAR T cells bind to targeted cancer cells, triggering them to activate, multiply, and destroy malignant cells. This direct recognition mechanism makes CAR T cells effective against specific types of leukemia, lymphoma, and multiple myeloma where these surface markers are consistently expressed. Their continuous proliferation within the patient’s body makes them a persistent therapy against cancer.
Tumor-Infiltrating Lymphocyte (TIL) therapy uses T cells that have naturally migrated into a patient’s tumor. These T cells are already primed to recognize the cancer’s unique characteristics. A portion of the patient’s tumor is surgically removed, and the TILs are extracted from this tissue in a laboratory.
After isolation, these naturally occurring anti-tumor T cells are grown to vast numbers outside the body using growth factors like interleukin-2 (IL-2). Once expanded, these TILs are re-infused into the patient, where they bolster the body’s existing immune response against the tumor. This approach capitalizes on the immune system’s intrinsic ability to identify and infiltrate cancerous tissues.
T-Cell Receptor (TCR) therapy is another form of adoptive cell therapy, distinct from CAR-T cells in its targeting mechanism. This therapy modifies a patient’s T cells to express a specific T-cell receptor (TCR) that recognizes cancer-related proteins. Unlike CARs that target surface antigens, TCRs recognize small protein fragments, called peptides, presented on the cell surface by Major Histocompatibility Complex (MHC) molecules.
This capability allows TCR T cells to target proteins on the cell surface and those inside the cancer cell, displayed via MHC. Targeting intracellular antigens expands the range of potential cancer targets, making TCR therapy relevant for solid tumors where many unique cancer proteins reside within the cell. However, TCR therapy requires a match between the patient’s MHC type and the engineered TCR, which can limit its universal applicability.
Conditions Treated with Adoptive Cell Therapy
Adoptive cell therapy has achieved success in treating various blood cancers, which affect the blood, bone marrow, and lymph nodes. It has demonstrated effectiveness in specific types of leukemia, such as acute lymphoblastic leukemia, and various forms of lymphoma, including certain types of large B-cell lymphoma. This therapy has also shown promise in treating multiple myeloma, a cancer of plasma cells.
The efficacy in blood cancers is partly due to the accessibility of cancer cells circulating in the blood or residing in the bone marrow, making them easier targets for the infused immune cells. For instance, CAR T-cell therapies targeting CD19 have transformed the treatment landscape for certain B-cell malignancies. These therapies offer an option for patients who have not responded to conventional treatments.
While blood cancers have seen primary uses, research and clinical trials are exploring adoptive cell therapy for solid tumors, which are abnormal tissue masses without cysts or liquid areas. Conditions like metastatic melanoma, non-small cell lung cancer, and gynecologic cancers are under investigation. Treating solid tumors presents a greater challenge because their complex microenvironment can suppress immune cell activity and physical barriers can hinder cell infiltration.
Despite these challenges, early results in some solid tumors, particularly melanoma with TIL therapy, have been encouraging. Ongoing research aims to overcome the hurdles posed by solid tumors, potentially through combination therapies or by enhancing the persistence and infiltration capabilities of engineered cells. Expanding ACT’s reach to a wider range of solid tumors remains a significant focus.
Beyond cancer, research is exploring the potential of adoptive cell therapy for non-cancerous conditions. Early investigations suggest applications in autoimmune diseases, such as lupus, where the immune system mistakenly attacks healthy tissues. Chronic infections are another area where ACT’s ability to precisely target specific cells could offer new therapeutic avenues.
Patient Experience and Side Effects
After adoptive cell infusion, patients undergo close monitoring, often requiring a hospital stay. This monitoring allows healthcare teams to observe the patient’s response and promptly manage potential side effects. The duration of inpatient monitoring varies, but patients are advised to remain near their treatment center for approximately 28 days following infusion.
One common side effect of adoptive cell therapy is Cytokine Release Syndrome (CRS). This occurs when activated, engineered immune cells release many signaling molecules called cytokines into the bloodstream, leading to a systemic inflammatory response. Symptoms of CRS can range from fever, fatigue, and muscle aches to more severe manifestations like low blood pressure and difficulty breathing.
While CRS can be serious, it is manageable with supportive care and specific medications, such as tocilizumab, which blocks the action of a key cytokine called IL-6. The severity of CRS can vary among patients, and medical teams are skilled in identifying and treating it to prevent more serious complications.
Another potential side effect is Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which affects the brain and nervous system. ICANS symptoms can appear as confusion, difficulty speaking (aphasia), tremors, headaches, or seizures. These neurological effects can occur alongside CRS or independently.
ICANS is temporary and treatable, often with corticosteroids or other interventions. Close neurological monitoring is a standard part of post-infusion care to detect symptoms early. While rare, severe cases of ICANS can lead to more serious neurological complications, highlighting the importance of specialized medical oversight during recovery.