Cell and gene therapy

Cell therapy uses healthy cells that come from either your body or a donor to target and eliminate cancer or abnormal cells. In some cases, cells may be changed in a lab before being returned to your body to fight disease. For example, in some cell therapies for cancer, your immune cells are “trained” to find, target, and destroy cancer cells.

Common approaches include:

• CAR T cell therapy: Reprograms T cells to find and attack cancer cells.
• T cell receptor (TCR) therapy: Modifies T cells to recognize specific cancer markers in solid tumors.
• Tumor infiltrating lymphocyte (TIL) therapy: Uses immune cells from a tumor that are grown and strengthened in a lab.
• Bone marrow or stem cell transplant Replaces damaged or diseased blood-forming cells with healthy ones to rebuild your blood cells and immune system.

Gene therapy rewrites the “instruction manual” to change how genes work inside cells, and therefore how the cells themselves work. This can help the body make the right proteins or stop harmful ones. New genetic instructions are delivered through a modified, harmless virus or similar lab-designed material that can be picked up naturally by the body. This delivery system, called a vector, delivers a new healthy gene or can eliminate a defective gene, allowing cells to function normally or, in ways designed determined by the new gene designed by the scientists and clinicians, respond to the updated genetic code and make needed changes.

Common approaches include:

• Gene addition: Adds a working copy of a gene to replace a faulty one.
• Gene editing: Changes or repairs DNA within cells to correct genetic mistakes.
• In vivo therapy: Delivers genetic material directly into the body through an injection or infusion.
• Ex vivo therapy: Removes and modifies cells outside the body and then returns them.

Some treatments use both cell therapy and gene therapy approaches together. With this method, cells are removed, genetically changed in the lab, and returned to the body. These modified cells can fight disease and help create new, healthy cells. This approach is used for health conditions like cancer and sickle cell disease.

These therapies address a wide range of inherited and acquired conditions of the blood and immune system, including:

• Sickle cell disease
• Beta thalassemia
• Hemophilia B
• Aplastic anemia
• Myelodysplastic syndromes 

Cell therapy for cancer uses your own immune system as a powerful tool to find and destroy tumors. Care may include treatment for:

• Blood cancers, like leukemia, lymphoma, and multiple myeloma 
• Melanoma
• Synovial sarcoma 

Pioneering research at Penn Medicine led to one of the first gene therapies for inherited vision loss. Luxturna, an FDA-approved treatment, can improve vision in people born with Leber congenital amaurosis (LCA), a type of early onset retinitis pigmentosa. Inherited retinal disease care specialists replace missing or faulty genes in the eye with healthy ones to help slow or stop disease progression.

Genetic alteration brings new options to people with rare neurological conditions. The Penn Neurogenetics Therapy Center leads early-phase clinical trials of gene-based therapies for neurological disorders, including:

• Spinal muscular atrophy
• Cerebral adrenoleukodystrophy

For therapies that use modified blood or stem cells, the first few weeks after infusion focus on a process called engraftment. This is the critical period when the new, modified cells travel to the bone marrow and begin creating healthy red blood cells, white blood cells, and platelets. Your care team closely monitors your blood counts to make sure the cells are working properly.

Depending on the therapy, recovery may involve a hospital stay lasting several days or weeks. Other treatments are done in an outpatient setting with frequent follow-up visits. Some people may need to stay close to the medical center for a period of time, so side effects can be managed quickly and recovery can be closely monitored.

As your body adjusts to treatment, temporary side effects like fatigue, nausea, fever, or flu-like symptoms are common.

Cell and gene therapies can temporarily weaken your immune system while your body recovers. During this time, you may be more likely to get infections and may need to avoid crowds or people who are sick. Some people also take medications to help prevent infection and support immune recovery.

Your care team monitors your immune function, blood counts, and overall health through regular follow-up visits and testing. As your body begins producing healthy new cells, immune function and energy levels often improve over time.

Recovery continues after you leave the hospital or infusion center. It’s normal to feel tired as your body uses energy to heal and build new cells. Depending on your treatment and condition, you may gradually return to work, exercise, school, and other daily activities over several weeks or months.

Your care team will explain any temporary physical limitations and help guide your recovery. Rehabilitation, which can include physical therapy and nutrition support, may also be part of your care plan.

Cell and gene therapies often require long-term follow-up to monitor effectiveness and immune recovery. At Penn Medicine, we continue tracking your progress through regular visits, blood tests, imaging, and other evaluations based on your condition and treatment.

Some gene therapies are designed to create long-lasting genetic changes inside cells. Because these therapies are still relatively new, the FDA may recommend monitoring for many years after treatment, sometimes up to 15 years. This long-term follow-up helps track how well the therapy is working and watch for delayed side effects.