Understanding TILs, CAR-T and BiTEs Immunotherapy Treatments

Over the last several decades, cellular immunotherapy has emerged as a promising treatment option for many types of cancer. A form of biological therapy, immunotherapy uses substances found naturally in the body. More specifically, it works by harnessing the power of the body’s immune system, a complex network of cells, tissues and organs that protects against infection by fighting off harmful invaders, such as viruses, bacteria and cancer. 

Through extensive research, scientists have discovered that certain immune cells known as lymphocytes (T cells) have a natural ability to identify, target and destroy tumor cells. Tumor-infiltrating lymphocyte (TIL) therapy and chimeric antigen receptor (CAR)-T cell therapy are one-time cancer immunotherapies that capitalize on the power of these immune cells. 

Engineered in a laboratory, Bispecific T-cell engagers (BiTEs) are a specialized subtype of BsAbs, bispecific antibodies (BsAbs). BiTes are proteins with a unique dual-binding ability that allows them to simultaneously bind to two different antigens, one on a cancer cell and one on an immune cell. By bringing these cells together, bispecific antibodies can enhance the precision and effectiveness of the body’s natural immune response to tumors.

Tumor-infiltrating lymphocyte therapy

Initially a revolutionary treatment option for melanoma, TIL therapy leverages the cancer-fighting ability of white blood cells known as tumor-infiltrating lymphocytes (TILs). It is an important treatment option for:

• Head and neck squamous cell carcinoma
• Advanced melanoma
• Lung cancer
• Genitourinary cancers
• and is being evaluated for a growing list of other malignancies

How does TIL therapy work? 

TIL therapy begins with the surgical removal of at least one cancerous tumor, which may be primary or metastatic. Typically, the surgeon will choose the tumor that is easiest to access and remove. This approach can help ensure a quick recovery, allowing the patient to begin the next phase of treatment as soon as possible.

The surgically removed tumor tissue will be sent to a lab, where the TILs within it will be isolated from the other tumor cells. The TILs will then be cultured and expanded (multiplied) with interleukin-2 (IL-2), a protein that promotes rapid cell growth. 

Once a large quantity of TILs has been successfully produced, the patient will receive conditioning chemotherapy to prepare their body for TIL therapy. By creating a more hospitable environment for the reinfused TILs, conditioning chemo can increase the likelihood that the cells will survive and multiply.

The TILs will be infused to the patient via a chest port. After entering the bloodstream, these powerful immune cells can circulate throughout the body to seek and destroy widespread cancer cells.

TIL therapy takes several weeks to complete. This time frame includes surgery to remove the tumor, preparation of the TILs in a lab, conditioning chemotherapy and TIL infusion. Because chemo can weaken the patient’s immune system making them more susceptible to infection, the infusion component of TIL therapy is performed on an inpatient basis.

What are the side effects of TIL therapy? 

In addition to increased risk of infection, the conditioning chemotherapy and IL-2 used during TIL therapy may cause other temporary side effects, such as: 

• Weakness and fatigue
• Fever and chills
• Nausea, vomiting and diarrhea
• Low blood cell counts
• Dizziness and headaches 

Chimeric antigen receptor-T cell therapy (CAR-T)

Much like TIL therapy, CAR-T cell therapy involves collecting, boosting and reinfusing T cells to improve the immune system’s response to cancer. However, TIL therapy is polyclonal, which means it can target many cancer antigens at once, and those markers are not necessarily known at the time of treatment. On the other hand, CAR-T cell therapy is monoclonal, which means it can target only one specific protein that is known to be found on the surface of the cancer cells. Additionally, the immune cells used in CAR-T cell therapy must be genetically modified in a lab so they will recognize the marker.

What types of cancer can be treated with CAR-T cell therapy?

CAR-T cell therapy is FDA-approved for treating certain blood cancers, including:

• Relapsed and refractory acute lymphoblastic leukemia in pediatric and young adult patients
• Relapsed and refractory diffuse large B cell lymphoma in adults
• Relapsed and refractory follicular lymphoma
• Relapsed and refractory mantle cell lymphoma
• Multiple myeloma
• Primary mediastinal B cell lymphoma

Research and clinical trials are ongoing to evaluate the effectiveness of CAR-T cell therapy in treating other types of cancer, including solid tumors.

How does CAR-T cell therapy work?

CAR-T cell therapy is a highly specialized and personalized treatment that begins with the collection of white blood cells from the patient’s blood. During a leukapheresis procedure, blood will be drawn through an intravenous (IV) line and passed through an apheresis machine, which will separate the T cells within it from the other blood components. The other blood components will be immediately reinfused to the patient via a second IV line. Leukapheresis can take up to several hours. When the procedure is complete, the isolated T cells will be sent to a lab for processing.

In the lab, the T cells will be genetically altered to add a custom CAR. This special receptor will bind to a specific marker found on the surface of the tumor cells. Because different cancers have different markers, the CAR must be tailored to the tumor. The genetically modified T cells will then be duplicated and prepared for reinfusion into the patient. 

To prepare the patient’s body for the reinfusion of the CAR-T cells and heighten the effectiveness of the treatment, conditioning chemotherapy may be administered beforehand.

What are the side effects of CAR-T cell therapy?

During the leukapheresis procedure, the patient may experience numbness, tingling sensations or muscle spasms due to a temporary drop in blood calcium. Usually, these effects can be managed by taking calcium, which may be administered by mouth or through an IV line.

While CAR-T cell therapy can be effective against certain difficult-to-treat cancers, it can sometimes cause potentially serious side effects, such as cytokine release syndrome (CRS), a severe immune system response triggered by the excessive release of certain chemicals (cytokines) into the bloodstream. Symptoms of CRS can include:

• Weakness and fatigue
• Difficulty breathing
• Fever, chills and other flu-like symptoms
• Nausea, vomiting and diarrhea
• Low blood cell counts
• Dizziness and headaches
• Muscle and joint pain
• Rapid heartbeat

In many cases, the side effects of CAR-T cell therapy can be managed with medication.

Bispecific T Cell Engagers (BiTEs)

Widely considered to be the next generation of monoclonal antibodies, bispecific antibodies take the monoclonal antibody treatment approach one step further.

 Engineered to bind to two different antigens at the same time—one on a tumor cell and one on an immune cell—these drugs have a dual-binding ability that can bring cancer-fighting immune cells into close proximity with tumor cells, further enhancing the immune system’s ability to fight cancer. BiTEs are a specialized subtype of BsAbs, which may signal a new era in cancer treatment.

What types of cancer can be treated with BiTEs?

BiTEs are being developed and used to treat several types of cancer, including:

• Acute lymphoblastic leukemia – Bispecific antibodies such as Blincyto (blinatumomab) can target CD19 on B cells and CD3 on T cells.
• Non-Hodgkin lymphoma (NHL) – Bispecific antibodies are being explored to target specific markers on B cells in various subtypes of NHL.
• Multiple myeloma – Bispecific antibodies targeting B cell maturation antigen (BCMA) on myeloma cells and CD3 on T cells are currently under study in clinical trials.
• Certain solid tumors – Researchers are investigating bispecific antibodies for treating lung cancer, colorectal cancer and ovarian cancer.

How do BiTEs work?

BiTEs can improve the likelihood of a successful attack against cancer by bringing the body’s own cancer-fighting cells directly into contact with the cancer cells and linking them together with a flexible linker peptide.

BiTEs are produced “off the shelf.” In other words, the patient’s cells are not needed to produce the drugs. Therefore, the patient does not have to travel to a designated site or undergo a medical collection procedure before the modified immune cells can be manufactured. This can lead to quicker treatment.

Usually, BiTEs treatment is administered via infusion into a vein. However, in some cases, the treatment can be administered subcutaneously (injected under the skin).

What are the side effects of BiTEs?

Like CAR T-cell therapy, BiTEs treatment may cause CRS, which is potentially serious and requires immediate medical attention. Other possible side effects of BiTEs include: 

• Mild inflammatory response due to T cell activation
• Fever, chills and other flu-like symptoms
• Low white blood cell counts (neutropenia)
• High C-reactive protein (CRP) counts

World-class care at Moffitt Cancer Center

Leading the charge to usher in a new era of cancer treatment, Moffitt was the first cancer center in the world to treat more than 1,000 patients with CAR-T cell therapy. Through extensive research and clinical trials, our dedicated scientists and clinicians are pioneering next-generation TIL therapies, CAR-T cell therapies and bispecific antibodies to harness the power of the immune system in the fight against cancer.

If you would like to learn more about immunotherapy for cancer, you can request an appointment with a specialist at Moffitt by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.