CAR-T cell therapy is a relatively new cancer treatment that has shown promising results in many clinical trials. Its success can be attributed to the fact that it uses the patient's own immune system to fight their cancer. However, like all medical treatments, it is not without its risks and side-effects. In this blog post, we will explore the side-effects of CAR-T cell therapy and how they can be managed.

What is CAR-T Cell Therapy?

CAR T-cell therapy is a method of utilizing T cells, a type of white blood cell, to combat cancer by modifying them in a laboratory setting. This modification enables the T cells to locate and eliminate cancer cells. CAR T-cell therapy is occasionally referred to as a form of gene therapy involving the genetic alteration of T cells to enhance their ability to attack cancer. This treatment can prove highly beneficial in addressing certain types of cancer, particularly when other treatment options have become ineffective.

According to TechSci Research report “CAR-T Cell Therapy Market – Global Industry Size, Share, Trends, Opportunity, and Forecast, 2017-2027 Segmented By Product Type (Yescarta (Axicabtagene Ciloleucel), Kymriah (Tisagenlecleucel), Tecartus (Brexucabtagene Autoleucel), Breyanzi (Lisocabtagene Maraleucel), Abecma (Idecabtagene Vicleucel), Others), By Tumor Type (Hematological Malignancies, Solid Tumors), By Indication (Diffused Large B-Cell Lymphoma (DLBCL), Acute Lymphoblastic Leukemia (ALL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Others), By Treatment Type (Single Treatment, Combination Treatment), By Targeted Antigen (CD 19, BCMA (B-Cell Maturation Antigen), Others), By End User (Hospitals, Specialty Clinics, Ambulatory Surgical Centers, Others), By Region, By Company,” the Global CAR-T cell therapy market stood at USD1709.00 million in 2021 and is expected to grow at a CAGR of 64.66% during the forecast period. This can be attributed to the increasing prevalence of different types of cancer globally. Additionally, the approval of new CAR-T cell therapies such as ABECMA (idecabtagene vicleucel) has increased the demand for CAR-T cell therapies for the treatment of cancer. Additionally, the flourishing pharmaceutical research expenditure by the private and government industries across different regions is expected to drive market growth during the forecast period.

The market growth is driven by various factors, such as focus on personalized medicine, growing prevalence of cancer, and increase in cell therapy clinical studies.

How CAR T-cell therapy works?

Immune receptors and foreign antigens

The immune system recognizes foreign substances in the body by detecting proteins known as antigens on the surface of those cells. T cells, a type of immune cells, possess their own receptors that bind to foreign antigens and activate other components of the immune system to eliminate the foreign substance.

The interaction between antigens and immune receptors can be likened to a lock and key mechanism. Just as a lock requires the correct key to be opened, each foreign antigen possesses a unique immune receptor that is capable of binding to it.

Cancer cells also display antigens, however, if the immune cells lack the appropriate receptors, they are unable to attach to the antigens and assist in the destruction of the cancer cells.

Chimeric antigen receptors (CARs)

In CAR T-cell therapies, T cells are extracted from the patient's blood and genetically modified in the laboratory by introducing a gene encoding a receptor known as a chimeric antigen receptor or CAR. This receptor facilitates the attachment of T cells to a specific cancer cell antigen. Subsequently, the CAR T cells are reintroduced into the patient.

As different types of cancer possess distinct antigens, each CAR is designed to target a specific cancer antigen. For instance, certain forms of leukemia or lymphoma exhibit an antigen called CD19. CAR T-cell therapies developed to treat these cancers are engineered to bind specifically to the CD19 antigen and are not effective against cancers lacking the CD19 antigen.

Approved CAR T-cell therapies

CAR T-cell therapies are approved by the US Food and Drug Administration (FDA) to treat some kinds of lymphomas and leukemias, as well as multiple myeloma. CAR T-cell therapy is typically used after other types of treatment have been tried.

The U.S. Food and Drug Administration (FDA) has approved several CAR T-cell therapies for patients with certain blood cancers that do not respond to chemotherapy and other treatments. Furthermore, this therapy is utilized in the management of patients who experience a relapse of blood cancer after previous successful treatments.

Examples of CAR T-cell therapies currently approved include:

·         Tisagenlecleucel, also known as tisa-cel (Kymriah)

·         Axicabtagene ciloleucel, also known as axi-cel (Yescarta)

·         Brexucabtagene autoleucel, also known as brexu-cel (Tecartus)

·         Lisocabtagene maraleucel, also known as liso-cel (Breyanzi)

·         Idecabtagene vicleucel, also known as ide-cel (Abecma)

·         Ciltacabtegene autoleucel, also known as cilta-cel (Carvykti)

Many other CAR T-cell therapies (and similar types of treatment) are now being studied in clinical trials, in the hope of treating other types of cancer as well.

Side-effects of CAR T-cell therapies:

1. Cytokine Release Syndrome (CRS):

One of the most common side-effects of CAR-T cell therapy is cytokine release syndrome. This condition is caused by the rapid release of cytokines when the CAR-T cells attack cancer cells. Symptoms of CRS can range from mild to severe and can include fever, chills, fatigue, nausea, and difficulty breathing. In severe cases, CRS can lead to multi-organ failure and even death. To manage this side-effect, patients are monitored closely and given medication to control their symptoms. In extreme cases, patients may require admission to the intensive care unit.

2. Neurological Toxicity:

Another potential side-effect of CAR-T cell therapy is neurological toxicity. This can manifest as confusion, seizures, and difficulty speaking or walking. The exact cause of neurological toxicity is not well understood, but it is thought to be caused by the immune system attacking healthy nerve cells. Patients experiencing this side-effect will be closely Some of the effects of neurotoxicity may appear immediately, while others can take months or years to manifest. monitored, and medication may be used to control their symptoms.

3. Infections:

Infection is a major concern for patients undergoing CAR-T cell therapy. This is because the treatment weakens the immune system, leaving patients vulnerable to infections. Infections can be bacterial, viral, or fungal, and can occur at any stage of the CAR-T cell therapy process, from conditioning chemotherapy to infusion of the modified immune cells. The most common infections include febrile neutropenia, cytokine release syndrome (CRS), and neurotoxicity.

Febrile neutropenia occurs when the white blood cell count drops below normal, making it difficult for the body to fight off infections. This can lead to a fever and other symptoms like chills or sweating. Patients who experience febrile neutropenia need hospitalization and might require antibiotics or other medication.

CRS is a systemic inflammatory response that occurs due to the rapid release of cytokines from the modified immune cells activated by CAR-T cell therapy. CRS can cause a cascade of symptoms ranging from fever, fatigue, and headache to more severe symptoms such as tachycardia, hypotension, and respiratory distress. CRS can also lead to multiple organ failure and be fatal in severe cases.

4. Tumor Lysis Syndrome:

Tumor lysis syndrome is a side-effect that occurs when cancer cells are destroyed more quickly than the body can eliminate them. This can lead to the release of toxins into the bloodstream, which can cause kidney damage and other complications. To prevent this from happening, patients are monitored closely and given IV fluids to help flush out the toxins. Tumor lysis syndrome is a condition that affects both adult and pediatric oncology patients undergoing chemotherapy, although it can also occur spontaneously. The symptoms observed in patients with tumor lysis syndrome are primarily caused by the release of intracellular chemical substances, leading to impaired organ functions. This can result in acute kidney injury (AKI), fatal arrhythmia, and even death. Due to the highly lethal nature of this condition, it is crucial to identify patients at a high risk of developing tumor lysis syndrome and promptly initiate preventative therapy. Swift and early recognition of the renal and metabolic disturbances associated with tumor lysis syndrome, along with timely initiation of treatment, can potentially be life-saving for patients.

5. Blood Clots:

Finally, CAR-T cell therapy has been known to increase the patient's risk of developing blood clots. This is because the treatment can cause inflammation, which can contribute to the formation of blood clots. Patients may need to take blood thinners to prevent this from happening.

The U.S. Food and Drug Administration (FDA) has granted approval to multiple CAR T-cell therapies for individuals with specific blood cancers unresponsive to chemotherapy and other treatments. Additionally, this therapy is employed in the treatment of individuals experiencing the recurrence of blood cancer following successful prior treatments.

CAR T-cell therapy is offered through risk evaluation and mitigation strategies (REMS). REMS make sure that healthcare providers are certified to offer the therapy and have the know-how to manage any serious side effects.

Top 5 Companies in the Global CAR T-Cell Therapy Market

1.Novartis AG:

Novartis AG is currently the leader in the Car T cell therapy market. Their product, Kymriah, was the first FDA-approved Car T cell therapy for cancer treatment. It has shown impressive results in clinical trials, and the company is now investing further in improving its product and exploring treatment options for different types of cancers. Novartis AG is working on reducing the treatment cost of Kymriah, which has been one of the major hurdles for widespread use.

2. Gilead Sciences Inc.:

Gilead Sciences Inc. is another top company that has invested heavily in the Car T cell therapy market. Its product, Yescarta, is designed to treat non-Hodgkin's lymphoma. The drug has received FDA approval and has shown a high level of effectiveness in clinical trials. Gilead Sciences' focus on developing drug candidates to target various types of cancer is one of the key reasons behind its success.

3. Celgene Corporation:

Celgene Corporation has a strong pipeline of Car T cell therapy candidates. One of their leading products, bb2121, is in phase III clinical trials to treat multiple myeloma. The company is also testing other Car T cell candidates to treat a range of hematological and solid tumors. Celgene is known for its research and development capabilities, and it is expected to produce several key Car T cell therapy products in the coming years.

4. bluebird bio Inc.:

bluebird bio Inc. has been making significant strides in the Car T cell therapy market. The company is developing a range of Car T cell candidates, including bb21217, for multiple myeloma and bb2128, for solid tumors. Their gene editing and therapy technologies are some of the most advanced in the industry, and the company is confident about their products' effectiveness.

5. Juno Therapeutics:

Juno Therapeutics has been involved in Car T cell therapy research for a long time. Their leading product, JCAR017, has shown exceptional efficacy in treating diffuse large B-cell lymphoma and other hematological malignancies. The company's focus is on exploring Car T cell candidates to treat solid tumors too.

Cancers now Treated with CAR T-cell therapy:

B-cell acute lymphoblastic leukemia (ALL)

This cancer affects the immature B lymphocytes or white blood cells when they’re growing in the bone marrow. Providers typically treat it with chemotherapy and bone marrow transplant.

According to TechSci Research report “Japan CAR-T Cell Therapy Market, By Product Type (Yescarta (Axicabtagene Ciloleucel), Kymriah (Tisagenlecleucel), Tecartus (Brexucabtagene Autoleucel), Breyanzi (Lisocabtagene Maraleucel), Abecma (Idecabtagene Vicleucel), Others), By Tumor Type (Hematological Malignancies, Solid Tumors), By Indication (Diffused Large B-Cell Lymphoma (DLBCL), Acute Lymphoblastic Leukemia (ALL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Others), By Treatment Type (Single Treatment, Combination Treatment), By Targeted Antigen (CD 19, BCMA (B-Cell Maturation Antigen), Others), By End User (Hospitals, Specialty Clinics, Ambulatory Surgical Centers, Others) By Region, Competition, Forecast & Opportunities 2019-2029,” Japan CAR-T Cell Therapy Market stood at USD 66.06 million in 2023 and is expected to grow at a robust rate of 13.44% during the forecast period. This can be ascribed to the growing prevalence of different types of cancer and need to find an effective treatment for the same. Cancer continues to be a significant health challenge, necessitating innovative approaches to treatment.

Conclusion:

Car T cell therapy is a breakthrough strategy in cancer treatment that holds enormous potential to transform the lives of patients. It is a personalized, targeted, and highly effective approach to fight cancer cells in the body. By genetic engineering a patient's T cells, the body's own immune system, Clinicians can provide a more effective response to the cancer. The therapy has already shown to have an important role in the treatment of patients with leukemia, lymphoma, and multiple myeloma. Still, the future of Car T cell therapy looks bright, with new research and developments ongoing. There is optimism for the possibility of expanding Car T cell therapy's application to other types of cancers and improving the patients' response to the therapy. With time and continued investment, it may become a critical pillar in the fight against cancer.

CAR-T cell therapy is an exciting new cancer treatment that has shown great promise in clinical trials. However, it is essential to be aware of the potential side-effects that can occur with this treatment. While some side-effects may be severe, they can often be managed with close monitoring and medication. It is important to remember that not all patients will experience these side-effects and that the benefits of CAR-T cell therapy may outweigh the risks for many patients.