What is Cancer Immunotherapy?

Immunotherapy is a groundbreaking cancer treatment that capitalizes on the power of the body’s own immune system to identify, attack and destroy cancerous cells. Unlike chemotherapy and radiation therapy, which directly target tumor cells, immunotherapy amplifies the body’s natural immune response to cancer. By leveraging the immune system’s exquisite specificity, immunotherapies significantly cause less collateral damage to healthy cells. This novel treatment approach can be effective in treating various cancers, including melanoma, leukemia and lung cancer.

Due to its potential to achieve a long-lasting treatment response with fewer side effects than conventional therapies, immunotherapy represents a breakthrough in cancer care. It can be a valuable treatment option for many patients, particularly those who have not responded well to traditional therapies.

What are the types of cancer immunotherapy? 

Cancer immunotherapy can take several forms. Current options include tumor-infiltrating lymphocyte therapy, chimeric antigen receptor-T cell therapy and bispecific T-cell engager therapy.

Tumor-infiltrating lymphocyte (TIL) therapy

An advanced and highly personalized form of immunotherapy, TIL therapy harnesses the power of the patient’s own immune cells to fight cancer. As the immune system naturally responds to cancerous cells, certain immune cells (T cells) may infiltrate a tumor. TIL therapy involves extracting these TILs from the tumor, expanding them to a quantity of billions in a laboratory and then reinfusing the expanded TILs into the patient.

TIL therapy has shown promise in treating solid tumors, such as melanoma, lung cancer and other cancers that are resistant to conventional therapies. It works by boosting the number of cancer-fighting cells in the body, enhancing the ability of the immune system to recognize and destroy cancerous cells​.

How is TIL therapy administered?

TIL therapy is administered through a multi-step process:

• Tumor removal – During a surgical procedure, a surgeon will remove a tumor sample, which will be sent to a laboratory for processing.
• Lymphodepletion – In the meantime, the patient will receive lymphodepleting chemotherapy to temporarily reduce the number of immune cells in their body and create space for new TILs to thrive and function effectively.
• TIL expansion – In the lab, the TILs in the tumor tissue will be isolated, cultured and expanded over several weeks, increasing the number of T cells that can recognize and target the tumor.
• TIL reinfusion – The expanded TILs will be intravenously reinfused into the patient’s body, where they will act as an army of immune cells specifically designed to seek out and destroy the cancer cells.
• Interleukin-2 (IL-2) support – After TIL reinfusion, the patient may receive IL-2, a cytokine that can boost the activity of the T cells and help them attack the tumor more effectively.

The entire process is conducted in a controlled medical environment with close monitoring to manage any side effects and ensure treatment effectiveness. 

What are the benefits and possible side effects of TIL therapy?

The benefits of TIL therapy include:

• Individualized cancer treatment – Because TIL therapy uses the patient’s own immune cells, it is highly personalized and can target the specific tumor cells in the patient’s body​.
• Effectiveness for solid tumors – TIL therapy has shown promise in treating several types of solid tumors, including melanoma, lung cancer and cervical cancer, some in cases where conventional treatments were ineffective​.
• Potential for long-lasting remission – After TIL therapy, some patients experience a durable response with long-term cancer control, even for metastatic cancer.

Side effects of TIL therapy that may develop shortly after TIL infusion are usually minor when compared to the side effects associated with many other cancer treatments. Your doctor will monitor you for signs like:

• Fever
• Low blood pressure
• Difficulty breathing
• Fatigue
• Immune-related side effects

TIL therapy is a promising but still evolving treatment, and further research is needed to refine its application and broaden its availability. Current limitations and challenges include:

• Complex and lengthy preparation – TIL therapy requires harvesting T cells from a patient’s tumor, expanding the cells in a laboratory and then reinfusing them. This labor-intensive process can take up to several weeks, during which time the cancer may progress​.
• Limited availability – Currently, TIL therapy is available only in a few specialized cancer centers, primarily for clinical trials. Because this advanced treatment requires highly specialized expertise and equipment, its widespread use is restricted.
• Suitability only for certain cancers – Although TIL therapy has shown promise in treating some solid tumors, such as melanoma, its effectiveness in other cancer types, including some lung cancers, is still being evaluated. It may not be suitable for cancers that do not allow TILs to naturally infiltrate the tumor​.
• Side effects and toxicity – Some patients experience severe side effects, such as CRS and immune-related toxicities, which require close medical monitoring. The use of IL-2 to support TILs can also cause significant side effects, including low blood counts and organ inflammation​.
• Challenges in consistent efficacy – While some patients achieve long-lasting remission with TIL therapy, the response rate can vary, and not all patients benefit. Many factors, such as the tumor type and the patient’s immune response and overall health, can affect the success of TIL therapy.

What are the prospects for TIL therapy?

The prospects for TIL therapy are encouraging, with ongoing research showing its potential as a transformative treatment for various cancers. Through clinical trials, scientists are investigating its broader applicability and the early results have been positive, especially in cancers that have not responded well to other treatments. Additionally, improvements in the production process and advancements in technology may make it more accessible in the future, and streamlining the cell expansion process and reducing the time required for treatment could help more patients benefit from TIL therapy.

The development of next-generation TIL therapies, such as genetically modified TILs with improved function and persistence, holds significant promise. These modifications—such as incorporating cytokines or knocking out inhibitory genes using clustered regularly interspaced short palindromic repeats (CRISPR) technology—could reduce side effects and improve treatment outcomes.

Chimeric antigen receptor (CAR)-T cell therapy

CAR-T cell therapy is a cutting-edge immunotherapy that modifies a patient’s own T cells to enhance their ability to recognize and attack cancer cells. After being extracted from the patient, the T cells are genetically engineered in a laboratory to express a CAR on their surface. The CAR is a synthetic receptor specifically designed to target proteins (antigens) found on the surface of cancer cells. Once reinfused into the patient, the modified T cells—now equipped with the CAR—can better identify and destroy cancer cells by binding to the targeted antigens, even if the cancer has previously evaded detection by the immune system​.

This advanced technology has shown considerable success, particularly in treating certain blood cancers, such as leukemia and lymphoma. Research is ongoing, and scientists continue to evaluate its effectiveness for other cancers.

How is CAR-T cell therapy administered?

CAR-T cell therapy is administered through a multi-step process:

• T cell collection – The patient's T cells will be collected through leukapheresis, which involves drawing blood and separating its components to isolate the T cells.
• T cell modification – In a laboratory, the T cells will be genetically modified to add a CAR, which will help them recognize and bind to cancer cells.
• Lymphodepletion – Before CAR-T cell infusion, the patient may receive a short course of lymphodepletion chemotherapy to temporarily reduce the number of immune cells in their body and create a more favorable environment for the CAR-T cells to expand and work effectively.
• CAR-T cell infusion – In a process similar to a blood transfusion, the modified CAR-T cells will be intravenously reinfused into the patient.
• Monitoring and supportive care – Following infusion, the patient will be closely monitored for side effects, such as CRS and neurological symptoms, which are potentially serious but can be managed with supportive care in a hospital setting.

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

CAR-T cell therapy can provide significant benefits, especially for patients with difficult-to-treat cancer. Examples include:

• A high level of effectiveness for blood cancers – CAR-T cell therapy has shown remarkable success in treating certain blood cancers, including B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). Many patients who did not respond to traditional treatments achieved long-term remission​.
• Personalized cancer therapy – Because the patient’s own T cells are modified, CAR-T cell therapy is highly individualized, allowing for targeted treatment specific to the patient’s tumor.
• Potential for long-lasting remission – After infusion, CAR-T cells can remain in the body and continue to provide immune protection against the cancer, offering the possibility of durable remission​.

That said, the potential for side effects requires careful monitoring and management. These include:

• CRS – A common and serious side effect of CAR-T cell therapy, CRS can occur if the infused CAR-T cells trigger an overly robust immune response. Symptoms can range from fever and low blood pressure to shortness of breath and organ dysfunction. If not properly managed, CRS can be life-threatening​.
• Neurological toxicities – During CAR-T cell therapy, some patients experience immune effector cell-associated neurotoxicity syndrome (ICANS), which can cause neurological issues such as mental confusion, difficulty speaking and seizures.
• Increased risk of infections – CAR-T cell therapy can weaken the immune system both during and after treatment, making the patient more susceptible to infection​.
• Low blood cell levels – Lymphodepletion chemotherapy before CAR-T cell infusion can temporarily reduce blood cells counts, increasing the risk of anemia, excessive bleeding and infection​.

What are the limitations and challenges of CAR-T cell therapy?

Current limitations of CAR-T cell therapy include:

• Effectiveness limited to certain cancers – CAR-T cell therapy is primarily effective in treating blood cancers, such as leukemia and lymphoma. Thus far, its success in treating solid tumors has been limited, mainly because solid tumors present unique challenges, such as a hostile tumor microenvironment and physical barriers that can make it difficult for CAR-T cells to penetrate and attack cancer cells effectively​.
• Potentially severe side effects – While highly effective, CAR-T cell therapy carries the risk of serious side effects, such as CRS and neurological toxicities. Managing these side effects requires intensive monitoring and specialized care, which limits the therapy to major medical centers with expertise in handling these complications.
• Limited duration of effectiveness – While CAR-T cell therapy can lead to long-lasting remission, not all patients experience a durable response. In some cases, the cancer recurs, and the CAR-T cells may lose their effectiveness over time​.
• Manufacturing complexity – Producing CAR-T cells is a time-consuming and labor-intensive process that involves collecting the patient’s T cells, genetically modifying and expanding them in a lab and then reinfusing them into the patient. This process can take several weeks, which may not be feasible for a patient with an aggressive, rapidly progressing cancer.
• High cost and limited accessibility – CAR-T cell therapy can be expensive, making it difficult for some patients to access and benefit from the treatment, especially in regions where healthcare coverage is limited​. Additionally, the complex manufacturing process further restricts its widespread availability​.

These challenges underscore the need for more research to improve the efficacy and accessibility of CAR-T cell therapy.

What are the prospects for CAR-T cell therapy?

The prospects for CAR-T cell therapy are promising, with ongoing research and advancements aimed at:

• Expanding its application beyond blood cancers – Researchers continue to explore the potential of CAR-T cell therapy in treating solid tumors, such as lung, breast and brain cancers. Challenges, such as tumor microenvironment barriers, are being addressed through novel strategies, such as combining CAR-T cell therapy with other treatments and engineering T cells to better survive and function within solid tumors.
• Creating next-generation CAR-T cells – Scientists are working to develop CAR-T cells with enhanced capabilities, such as targeting multiple cancer antigens simultaneously and resisting suppression by the tumor environment. For instance, CRISPR technology could improve CAR-T cell longevity and efficacy.
• Reducing side effects – Researchers are working to address the severe complications of CAR-T cell therapy, such as CRS and neurological symptoms. Strategies include creating “switchable” CAR-T cells that can be turned off in case of toxicity and modifying the dosage and timing​ of treatment.
• Broadening accessibility – Efforts are underway to streamline the manufacturing process for CAR-T cell therapy to make the treatment more accessible and less costly. Strategies include developing off-the-shelf CAR-T cells from healthy donors (allogeneic CAR-T cell therapy) as an alternative to using the patient’s own T cells, which could reduce costs and treatment time.

Bispecific T-cell engager (BiTE) therapy

Bispecific T-cell engagers (BiTEs) are lab-engineered proteins designed to enhance the ability of the body’s immune system to target and destroy cancer cells. This innovative approach to cancer immunotherapy works by linking T cells—a critical component of the immune system—to cancer cells. 

BiTEs have two binding sites: one end attaches to the CD3 receptor on T cells, while the other binds to a specific tumor-associated antigen found on cancer cells, such as DLL3 or CD19. This dual-binding capability brings the T cells into proximity with the cancer cells, facilitating a precise immune attack. Once linked, the T cells become activated and release cytotoxic molecules that directly pursue and eliminate the cancer cells. This process bypasses the typical limitations of T cell recognition, allowing the immune system to home in on cancer cells more efficiently and accurately.

How is BiTE therapy administered?

Typically, BiTE therapy is administered via intravenous (IV) infusion. The duration and frequency of the infusions can vary depending on the specific BiTE therapy and cancer type. For example, some patients receive a continuous IV infusion over several days or weeks in a hospital. The treatment must be administered under careful medical supervision because it can trigger a strong immune response that requires monitoring both during and after the infusions. The goal of BiTE therapy is to continuously engage the patient’s T cells with cancer cells, facilitating an ongoing immune attack on the tumor.

What are the benefits and possible side effects of BiTE therapy?

The potential benefits of BiTE therapy include:

• Enhanced immune response – BiTE therapy effectively redirects the patient’s T cells to target and destroy cancer cells by directly linking them to specific tumor antigens. This can enhance the ability of the immune system to fight cancer, even in cases where it might not naturally recognize the cancer cells.
• Precise tumor targeting – BiTEs are designed to specifically seek out tumor-associated antigens, minimizing any damage to healthy cells.
• Effectiveness for treatment-resistant cancers – BiTE therapy has shown success in treating tumors that are resistant to other treatments, such as certain leukemias and lung cancers, providing a new option for some patients with limited treatment choices​.

Possible side effects of BiTE therapy include:

• CRS – A common and potentially serious complication of BiTE therapy, CRS can occur if the T cells release too many cytokines, which can cause symptoms such as fever, fatigue, low blood pressure and, in severe cases, organ dysfunction.
• Neurological toxicity – ICANS, a group of neurological symptoms associated with BiTE therapy, can cause mental confusion, seizures and speech difficulties.
• Gastrointestinal distress – Other common side effects include fatigue, nausea, decreased appetite, and gastrointestinal issues such as constipation​.

While BiTE therapy can offer significant benefits for targeting difficult-to-treat cancers, careful monitoring is required to manage its potential side effects.

What are the limitations and challenges of BiTE therapy?

While BiTE therapy represents a significant advancement in cancer treatment, it does have some limitations, such as:

• Short half-life and continuous infusion requirement – Because BiTE molecules break down quickly in the body, the treatment often necessitates continuous IV infusion over several days or weeks to maintain therapeutic levels of the drug. This can present logistical challenges for some patients.
• Limited effectiveness for certain cancers – Due to the complexity of the solid tumor microenvironment and the physical barriers that can prevent T cells from efficiently reaching and infiltrating the tumor, BiTEs are less effective for solid tumors than blood cancers.
• Potentially severe side effects – BiTE therapy can trigger CRS and neurological toxicity, both of which can lead to serious complications that require immediate medical attention​.
• Development of resistance – Over time, some patients develop resistance to BiTE therapy as the cancer cells alter or reduce the expression of the targeted antigen, making it more difficult for the BiTE to bind and engage the T cells​.
• Limited target availability – BiTE therapy relies on the presence of specific tumor-associated antigens for targeting. Not all cancers express these antigens, limiting the range of cancers that BiTEs can effectively​ treat.

These challenges highlight the need for further research to further improve BiTE therapy, particularly for treating solid tumors and managing side effects.

What are the prospects for BiTE therapy?

The prospects for BiTE therapy are promising, with ongoing research aimed at expanding its use beyond blood cancers. Scientists are currently exploring strategies to overcome the challenges inherent in treating solid tumors, such as enhancing T-cell infiltration into tumor sites and modifying the tumor microenvironment. Additionally, new BiTEs targeting different tumor-associated antigens could broaden the range of cancers that can be treated. 

Advances in engineering more stable BiTE molecules with longer half-lives could reduce the need for continuous infusions, making the therapy more convenient for patients​. Despite challenges such as CRS and neurological toxicities, the potential for BiTEs to provide a targeted and effective cancer treatment remains strong, and ongoing clinical trials are expected to continue to enhance its effectiveness​.

Chemotherapy vs. immunotherapy 

The key difference between chemotherapy and immunotherapy lies in each treatment’s mechanism of action. Used as a first-line therapy for many types of cancer, chemotherapy is a systemic treatment that utilizes chemical agents (drugs) to destroy rapidly dividing cells throughout the body, including cancer cells. However, chemo is not specific to cancer cells. Instead, the treatment affects all fast-growing cells, including healthy cells in the hair follicles and gastrointestinal tract. For this reason, chemotherapy often causes disruptive side effects, such as nausea, vomiting and hair loss. 

In contrast, immunotherapy is a more targeted approach to cancer treatment, focusing on boosting the body’s natural immune response to cancer while sparing healthy cells. Additionally, as a form of precision medicine. immunotherapy can be accurately tailored to the specific patient and cancer.

The prospects for cancer immunotherapy

The future of cancer treatment is likely to see more combined therapies that integrate both chemotherapy and immunotherapy to improve patient outcomes. By combining the direct cell-destroying effects of chemotherapy with the immune-boosting capabilities of immunotherapy, these treatments can work synergistically to target cancer cells more effectively. For instance, after chemotherapy reduces the size of a tumor, immunotherapy can recognize and attack the remaining cancer cells more efficiently. Furthermore, immunotherapy may help prevent a recurrence by improving the immune system’s long-term memory of cancer cells. This combined approach is being actively explored in clinical trials and could potentially lead to a positive treatment response and long-lasting remission in a wide range of cancers.

Benefit from world-class care at Moffitt Cancer Center

Moffitt has been a driving force in getting several cellular immunotherapies approved by the U.S. Food and Drug Administration (FDA), and we continue to lead the way in expanding the immunotherapy options for our patients. 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.