Adoptive immunotherapy uses a patient’s own immune cells to combat diseases, primarily cancer. This cellular therapy involves collecting immune cells, modifying them in a laboratory, and then reinfusing them into the patient. This personalized treatment allows for a targeted attack against diseased cells, leveraging the body’s natural defense mechanisms.
Harnessing the Immune System
The immune system is a complex network of cells and organs designed to protect the body from foreign invaders and abnormal cells, including cancer cells. Lymphocytes, a type of white blood cell, are central to this defense. T-cells, for example, are lymphocytes that can recognize and attack foreign or abnormal cells. Natural Killer (NK) cells also play a role as part of the innate immune system, capable of eliminating infected or malignant cells without prior activation.
Despite these capabilities, the immune system sometimes struggles to eliminate cancer effectively. Cancer cells can develop mechanisms to evade detection by immune cells, such as tricking the immune system or activating “checkpoint” processes that halt the immune response. This evasion allows tumors to grow and spread. Adoptive immunotherapy aims to overcome these limitations by enhancing the number and function of immune cells, or by redirecting them to specifically target cancer cells.
Key Types of Adoptive Immunotherapy
CAR T-cell Therapy
Chimeric Antigen Receptor (CAR) T-cell therapy involves genetically engineering a patient’s T-cells to detect and destroy cancer cells. Scientists introduce a gene for a Chimeric Antigen Receptor (CAR) onto the surface of these T-cells. This CAR allows modified T-cells to specifically recognize and bind to certain proteins, or antigens, found on cancer cell surfaces. Once bound, CAR T-cells activate, proliferate, and release cytotoxic molecules to directly kill cancer cells, while also stimulating other immune responses. This therapy has shown success, particularly in treating certain blood cancers like leukemia and lymphoma.
Tumor-Infiltrating Lymphocyte (TIL) Therapy
Tumor-Infiltrating Lymphocyte (TIL) therapy utilizes T-cells that have naturally migrated into a patient’s tumor. These TILs are often already fighting the cancer but may be insufficient in number or suppressed by the tumor’s microenvironment. A piece of the patient’s tumor is surgically removed, and the TILs are isolated. These isolated cells are then expanded to billions in a laboratory. The expanded, highly active TILs are then reinfused into the patient, where they can seek out and destroy cancer cells throughout the body.
T-cell Receptor (TCR) Therapy
T-cell Receptor (TCR) therapy involves genetically engineering T-cells to express a specific T-cell Receptor that can recognize intracellular cancer proteins. Unlike CAR T-cells which target surface antigens, TCRs recognize small protein fragments, called peptides, presented on the cell surface by Major Histocompatibility Complex (MHC) molecules. This allows TCR T-cells to target a broader range of cancer antigens, including those hidden inside the cell, making them promising for solid tumors. The patient’s T-cells are harvested, modified in the lab with the engineered TCR gene, and then expanded before being reinfused.
Natural Killer (NK) Cell Therapy
Natural Killer (NK) cell therapy harnesses the innate immune system’s NK cells, which can recognize and kill abnormal cells without prior activation or specific antigen presentation. NK cells can be sourced from either the patient (autologous) or a healthy donor (allogeneic), a notable difference from T-cell therapies. The collected NK cells are then expanded in the laboratory to increase their numbers and enhance their cancer-fighting capabilities. Sometimes, NK cells are further modified to express Chimeric Antigen Receptors (CARs) to specifically target certain cancer cells, similar to CAR T-cell therapy.
The Treatment Process
The journey for a patient undergoing adoptive immunotherapy typically begins with apheresis. During this process, a patient’s blood is drawn, and a machine separates out the immune cells, returning the remaining blood components to the body. This collection usually takes a few hours.
Once collected, the immune cells are transported to a specialized laboratory for processing. Depending on the therapy type, these cells may be genetically engineered, for instance, to introduce a CAR or a specific TCR. Following modification, the cells are expanded to vast numbers in a controlled environment. This expansion phase can take several weeks.
Before reinfusion, patients often receive a preparatory regimen, which may include a brief course of chemotherapy. This conditioning chemotherapy helps reduce existing immune cells, creating a more favorable environment for the newly infused cells to engraft and multiply. After conditioning, the engineered or expanded cells are infused back into the patient, similar to a blood transfusion. Following infusion, patients are closely monitored in the hospital for a period, often a minimum of two weeks, to track their response and manage potential side effects.
Patient Outcomes and Considerations
Adoptive immunotherapy has shown significant responses in patients with certain cancers, with some achieving long-term remission. For instance, adoptive transfer of tumor-infiltrating lymphocytes (TILs) has shown objective tumor regressions in approximately 50% of patients with metastatic melanoma. TCR T-cell therapy has shown objective clinical responses in patients with metastatic melanoma and synovial sarcoma. NK cell transfer immunotherapy, when added to standard treatment for solid cancers, has increased overall clinical response rates by 44% and complete response rates by 67%.
Despite these outcomes, patients may experience potential side effects. Cytokine Release Syndrome (CRS) is a common adverse event, occurring as activated immune cells release inflammatory chemicals into the bloodstream. Symptoms can range from fever and fatigue to low blood pressure and difficulty breathing. Immune effector cell-associated neurotoxicity syndrome (ICANS) involves effects on the nervous system, with symptoms like confusion, language difficulties, and seizures.
These side effects typically appear within one to three weeks after cell infusion, though delayed onset can occur, and ICANS often accompanies CRS. Medical teams closely monitor patients for these and other general side effects, such as fatigue, rash, or infections. Management strategies for CRS often involve medications like tocilizumab, sometimes combined with corticosteroids, while ICANS is primarily managed with corticosteroids. Close medical supervision and supportive care are provided to address these considerations.