Immunotherapies – Uses and Effects

If you are considering immunotherapies or if immunotherapy has been prescribed for you, this page is designed to help you best understand what this treatment involves, what it is, and what it does. We provide the history, uses, effects on cancer, and side-effects. We believe that it is very helpful for each of us to understand what we're engaging in and what the effects are so that we can make the best choices possible and participate in ways that bring about our greatest level of health and recovery. There are certainly other immunotherapies available, and we will add those as well as we continue to build out the content on this website.

Table of Contents:

  1. 10 Prominent immunotherapies

Executive Summary

  • Immunotherapy is a type of cancer treatment that helps the body's immune system fight cancer. It works by either boosting the immune system or helping it recognize and attack cancer cells. There are several types of immunotherapies, each with its own unique way of working.

  • Pembrolizumab (Keytruda) and Nivolumab (Opdivo) are drugs that block a protein called PD-1, which cancer cells use to hide from the immune system. By blocking PD-1, these drugs allow the immune system to recognize and attack cancer cells. They're used to treat various types of cancer, including melanoma and lung cancer.

  • Ipilimumab (Yervoy) works by blocking a different protein called CTLA-4, which acts as an "off switch" for T cells, a type of immune cell. By blocking this off switch, Ipilimumab allows T cells to remain active and attack cancer cells. It's mainly used to treat melanoma.

  • Atezolizumab (Tecentriq) is similar to Pembrolizumab and Nivolumab, but it targets PD-L1 instead of PD-1. It's used to treat several types of cancer, including bladder cancer and certain types of breast cancer. Like other immunotherapies, it helps the immune system recognize and attack cancer cells.

  • CAR-T cell therapy, including drugs like Kymriah and Yescarta, is a groundbreaking treatment that involves modifying a patient's own T cells to fight cancer. The modified T cells are given back to the patient, where they can recognize and attack cancer cells. This therapy has shown promising results in certain blood cancers.

  • Durvalumab (Imfinzi) is another drug that targets PD-L1, similar to Atezolizumab. It's used to treat certain types of lung cancer and bladder cancer. By blocking PD-L1, it helps keep T cells active and able to fight cancer cells.

  • Sipuleucel-T (Provenge) is a unique immunotherapy used for prostate cancer. It involves taking a patient's own immune cells, exposing them to a protein found in prostate cancer, and then giving them back to the patient. This helps the immune system recognize and attack prostate cancer cells.

  • Avelumab (Bavencio) and Cemiplimab (Libtayo) are newer immunotherapies that also target the PD-1/PD-L1 pathway. They're used to treat various types of cancer, including a rare skin cancer called Merkel cell carcinoma and a common type of skin cancer called cutaneous squamous cell carcinoma.

  • While immunotherapies can be very effective, they can also cause side effects related to an overactive immune system. These can include inflammation in various parts of the body, such as the lungs, liver, or intestines. Doctors need to monitor patients closely and manage these side effects.

  • Immunotherapy is a rapidly evolving field, with new treatments being developed and tested all the time. Researchers are working on ways to make these treatments more effective, reduce side effects, and use them to treat more types of cancer. The success of immunotherapy has transformed cancer treatment and offers hope for many patients.

Here are 10 prominent immunotherapies, detailing their effects and uses:

Click the title of each immunotherapy treatment for more information.

Pembrolizumab (Keytruda)

  • Effect: PD-1 inhibitor that blocks the interaction between PD-1 and its ligands, preventing cancer cells from escaping immune detection.

  • Use: Used in melanoma, lung cancer, head and neck cancer, and more.

Atezolizumab (Tecentriq)

  • Effect: PD-L1 inhibitor that blocks the interaction between PD-L1 and PD-1, allowing the immune system to recognize and attack cancer cells.

  • Use: Used in bladder cancer, lung cancer, and triple-negative breast cancer.

Sipuleucel-T (Provenge)

  • Effect: A personalized vaccine that stimulates an immune response against prostate cancer cells.

  • Use: Used in metastatic hormone-resistant prostate cancer.

Tisagenlecleucel (Kymriah)

  • Effect: A CAR-T cell therapy designed to target CD19, a protein on the surface of certain types of leukemia and lymphoma.

  • Use: Approved for B-cell acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL).

Nivolumab (Opdivo)

  • Effect: Another PD-1 inhibitor, similar to Pembrolizumab, allowing T cells to recognize and attack cancer cells.

  • Use: Used in melanoma, lung cancer, kidney cancer, and others.

CAR-T Cell Therapies (Kymriah, Yescarta)

  • Effect: Utilizes genetically engineered T cells with chimeric antigen receptors (CAR) to target specific cancer antigens.

  • Use: Used in certain types of lymphoma and acute lymphoblastic leukemia (ALL).

Avelumab (Bavencio)

  • Effect: A PD-L1 inhibitor, which helps to boost immune response against cancer cells.

  • Use: Approved for Merkel cell carcinoma and urothelial carcinoma.

Ipilimumab (Yervoy)

  • Effect: CTLA-4 inhibitor that enhances T-cell activation and proliferation, promoting an immune response against cancer cells.

  • Use: Commonly used in melanoma, often in combination with Nivolumab.

Durvalumab (Imfinzi)

  • Effect: Another PD-L1 inhibitor, enhancing T-cell function to better target cancer cells.

  • Use: Used in bladder cancer and Stage III non-small cell lung cancer (NSCLC) that can't be removed by surgery.

Cemiplimab (Libtayo)

  • Effect: PD-1 inhibitor, similar in action to Pembrolizumab and Nivolumab.

  • Use: Approved for cutaneous squamous cell carcinoma.

These immunotherapies have diverse mechanisms of action that generally work by boosting the immune system's ability to detect and fight cancer. The use of these therapies is often guided by specific genetic or protein markers present within the cancer. Immunotherapies have provided new options for previously hard-to-treat cancers and are being actively investigated in various combinations and settings to further enhance their efficacy. Side effects related to immune activation, such as autoimmune reactions, are unique challenges in the administration of these therapies and require careful management.

History:

Pembrolizumab was approved by the FDA in 2014. Its development marked a turning point in cancer therapy, providing a new way to treat cancer by harnessing the immune system. It became the first PD-1 inhibitor approved in the United States.

Pembrolizumab (Keytruda)

Pembrolizumab (Keytruda) is an immunotherapy drug that has brought about significant changes in cancer treatment. Here's a comprehensive look:

Mechanism of Action – Cancer Cells:

Pembrolizumab's mechanism centers around the inhibition of the PD-1 pathway:

  • PD-1 Blockade: By binding to PD-1, Pembrolizumab blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

  • Enhancing Immune Response: By inhibiting PD-1, it boosts the T cells' ability to recognize and attack cancer cells, overcoming the "brakes" that cancer cells apply to the immune system.

  • Promoting Tumor Infiltration: It can increase the infiltration of immune cells into the tumor, promoting a more effective immune attack.

Use:

Pembrolizumab has a broad spectrum of uses, including:

  • Melanoma: Both unresectable and metastatic.

  • Non-Small Cell Lung Cancer: Especially when tumors express PD-L1.

  • Head and Neck Squamous Cell Cancer: As primary treatment or after failure of other treatments.

  • Hodgkin's Lymphoma: In relapsed or refractory cases.

  • Bladder Cancer: Particularly urothelial carcinoma.

  • Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Cancers: Regardless of the tissue of origin.

Chemistry:

Pembrolizumab is a humanized monoclonal antibody. It specifically targets the programmed death receptor-1 (PD-1), a protein that plays a key role in regulating the immune system's response to cells, including cancer cells.

Mechanism of Action – Healthy Cells:

While Pembrolizumab is designed to enhance the immune system's ability to fight cancer, this activation can also lead to autoimmune-like side effects:

  • Immune-Related Adverse Effects: These can affect almost any organ system, including the skin (rashes), gastrointestinal tract (colitis), liver (hepatitis), and endocrine glands (thyroiditis).

  • Infusion Reactions: Some patients may experience reactions during or after the infusion.

Conclusion:

Pembrolizumab represents one of the pioneering efforts in the field of immunotherapy, showing remarkable effectiveness across a wide variety of cancers. By blocking PD-1, it enables the immune system to attack cancer more effectively. However, this also means that careful monitoring and management of immune-related side effects are essential. Its use continues to expand, and ongoing research is exploring its potential in combination with other therapies and in various settings and stages of cancer.

History:

Nivolumab was approved by the FDA in 2014, shortly after the approval of Pembrolizumab. It became the first PD-1 inhibitor approved for the treatment of advanced melanoma, and its approval opened doors to more research and development in immunotherapies targeting the PD-1/PD-L1 pathway.

Nivolumab (Opdivo)

Nivolumab (Opdivo) is another remarkable immunotherapy that has become a cornerstone in modern cancer treatment. Here's an in-depth look:

Mechanism of Action – Cancer Cells:

Nivolumab works by targeting the PD-1 pathway:

  • PD-1 Blockade: By binding to PD-1, Nivolumab prevents the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which are often overexpressed on cancer cells.

  • Restoring Immune Response: This blockade removes the “brakes” on the immune system, allowing T cells to recognize and attack cancer cells more effectively.

Promoting Anti-Tumor Activity: This enhanced immune response can shrink tumors and even lead to long-term control or cure in some patients.

Use:

Nivolumab is used in several types of cancer, including:

  • Melanoma: Both as a single agent and in combination with Ipilimumab.

  • Non-Small Cell Lung Cancer: Especially in cases where tumors express PD-L1.

  • Kidney Cancer: Often in combination with other agents like Ipilimumab.

  • Hodgkin's Lymphoma: In cases that have relapsed or become refractory after other treatments.

  • Head and Neck Cancer: For recurrent or metastatic cases.

Bladder Cancer: Particularly for urothelial carcinoma.

Chemistry:

Nivolumab is a fully human monoclonal antibody. It specifically binds to the programmed death-1 (PD-1) receptor, which is present on T cells and some other immune cells.

Mechanism of Action – Healthy Cells:

Nivolumab’s action isn't without potential side effects, as stimulating the immune system can cause it to attack normal tissues:

  • Immune-Mediated Side Effects: These can occur in any organ system and may require immunosuppressive treatment. Examples include colitis, hepatitis, pneumonitis, and endocrinopathies.

  • Infusion Reactions: Some patients might experience reactions during or after infusion.

Conclusion:

Nivolumab has significantly impacted the treatment landscape across various cancer types. Its ability to unleash the immune system's potential to fight cancer has led to remarkable outcomes, especially in cancers previously considered difficult to treat. Its development has not only improved patient outcomes but also spurred further innovation in the field of immunotherapy. Like other immune checkpoint inhibitors, careful monitoring and management of immune-related adverse effects are vital for its safe and effective use. The ongoing research into Nivolumab continues to expand its applicability, with more indications and combination therapies being explored.

History:

Ipilimumab was approved by the FDA in 2011, becoming the first approved therapy to target CTLA-4, a crucial immune checkpoint. Its approval marked a significant shift in cancer treatment, highlighting the importance of engaging the immune system to fight tumors.

Ipilimumab (Yervoy)

Ipilimumab (Yervoy) has played a pioneering role in the field of cancer immunotherapy. Here's a detailed look:

Mechanism of Action – Cancer Cells:

Ipilimumab functions by interacting with the CTLA-4 pathway:

  • CTLA-4 Blockade: CTLA-4 is a protein that acts as an "off-switch" for T cells. Ipilimumab binds to CTLA-4, blocking this off-switch.

  • Enhancing Immune Response: By blocking CTLA-4, Ipilimumab increases T-cell activation and proliferation, boosting the immune system's ability to attack cancer cells.

  • Potential for Long-Term Control: Some patients treated with Ipilimumab experience lasting tumor control, pointing to an ongoing immune response against the tumor.

Use:

Ipilimumab has been utilized in different types of cancer, including:

  • Melanoma: It was initially approved for advanced melanoma and has since been used in adjuvant settings as well.

  • Renal Cell Carcinoma: Often used in combination with Nivolumab.

Colorectal Cancer: Specifically for those with certain genetic features like microsatellite instability-high (MSI-H).

Chemistry:

Ipilimumab is a monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a receptor on T cells.

Mechanism of Action – Healthy Cells:

While Ipilimumab's action is vital for stimulating the immune system against cancer, it can also cause the immune system to attack normal tissues:

  • Immune-Related Adverse Effects: Side effects can affect various organs, including the skin (rash), gastrointestinal tract (colitis), liver (hepatitis), and endocrine glands (thyroid or pituitary dysfunction).

Severe Toxicities: Rarely, severe or even fatal immune-related adverse effects may occur.

Conclusion:

Ipilimumab has been a trailblazer in the field of cancer immunotherapy, showing that targeting immune checkpoints could translate to meaningful clinical benefits. Its mechanism of blocking CTLA-4 to stimulate an immune response against cancer cells has paved the way for subsequent therapies targeting other checkpoints like PD-1. As with other immunotherapies, the unique side effect profile necessitates careful monitoring and may require immunosuppressive medications to manage. Ipilimumab's introduction has had a lasting impact on the landscape of cancer treatment, and ongoing research is examining its potential in various combinations and cancer types.

Atezolizumab (Tecentriq)

Atezolizumab (Tecentriq) is another important immunotherapy that has found its place in modern oncology. Let's dive into the details:

History:

Atezolizumab was approved by the FDA in 2016, making it one of the first immunotherapies to target the PD-L1 pathway. It has since been a key player in various therapeutic strategies.

Mechanism of Action – Cancer Cells:

Atezolizumab's mode of action involves the PD-L1 pathway:

  • PD-L1 Blockade: By binding to PD-L1, Atezolizumab prevents it from interacting with PD-1 and B7.1, receptors found on T cells.

  • Enhancing Immune Response: This blockade helps T cells recognize and attack cancer cells, thereby augmenting the body's immune response against tumors.

Restoring Anti-Tumor Immunity: It may restore the anti-tumor activity of specific immune cells, such as TILs (tumor-infiltrating lymphocytes).

Use:

Atezolizumab has been approved for a variety of cancer types:

  • Bladder Cancer: Particularly for urothelial carcinoma, in both locally advanced and metastatic settings.

  • Non-Small Cell Lung Cancer (NSCLC): Especially when tumors express PD-L1.

  • Triple-Negative Breast Cancer (TNBC): Used in combination with chemotherapy for PD-L1-positive metastatic TNBC.

Small Cell Lung Cancer (SCLC): In combination with chemotherapy for extensive-stage SCLC.

Chemistry:

Atezolizumab is a monoclonal antibody that binds to programmed death-ligand 1 (PD-L1), which is expressed on many cancer cells and immune cells.

Mechanism of Action – Healthy Cells:

While Atezolizumab's action is essential in stimulating the immune system, it may cause unintended consequences:

  • Immune-Related Adverse Effects: Similar to other checkpoint inhibitors, side effects can involve various organs like the skin, gastrointestinal tract, liver, and endocrine system.

Potential Severe Reactions: Rare, but serious, side effects might occur, requiring careful management and potential discontinuation of the therapy.

Conclusion:

Atezolizumab has proven to be a valuable addition to the toolkit of cancer immunotherapies. Its unique action on the PD-L1 pathway provides a complementary approach to other PD-1 and CTLA-4 inhibitors. The ability to target PD-L1 specifically allows for a broad spectrum of applications across various types of cancer, sometimes in combination with other treatments like chemotherapy. The continuing research into Atezolizumab's mechanism of action, efficacy, and safety profile is likely to lead to further refinements and expansions in its therapeutic applications. As with other immunotherapies, clinicians must be mindful of its unique immune-related side effects, managing them proactively to maximize patient outcomes.

CAR-T (Chimeric Antigen Receptor T-cell)

CAR-T (Chimeric Antigen Receptor T-cell) therapies are groundbreaking cancer treatments that utilize a patient's own immune system to fight cancer. Two of the most notable CAR-T therapies are Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel). Here’s an in-depth look:

History:

  • Kymriah: Approved by the FDA in 2017, Kymriah became the first CAR-T cell therapy to receive commercial approval. It initially was approved for pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

  • Yescarta: Also approved in 2017, Yescarta was initially indicated for adult patients with relapsed or refractory large B-cell lymphoma.

Mechanism of Action – Cancer Cells:

Both therapies work through similar mechanisms:

  • T-cell Modification: Patient's T cells are collected and genetically modified to express a CAR that can recognize CD19 on cancer cells.

  • T-cell Expansion: These modified T cells are multiplied in the laboratory.

  • Infusion Back into the Patient: The CAR-T cells are then infused back into the patient, where they can locate and destroy CD19-expressing cancer cells.

Use:

Kymriah:

  • B-cell ALL: For pediatric and young adult patients with relapsed or refractory disease.

  • Diffuse Large B-cell Lymphoma (DLBCL): For adult patients with relapsed or refractory DLBCL.

Yescarta:

  • Large B-cell Lymphoma: Including DLBCL, primary mediastinal large B-cell lymphoma, and transformed follicular lymphoma, for adult patients with relapsed or refractory disease.

Chemistry:

CAR-T therapies involve genetic modification of a patient's T cells to express a chimeric antigen receptor (CAR) that targets a specific antigen on cancer cells.

  • Kymriah: Targets CD19, a protein on the surface of B cells.

  • Yescarta: Also targets CD19.

Mechanism of Action – Healthy Cells:

The targeting of CD19 also affects normal B cells, leading to B-cell aplasia. The process may also trigger:

  • Cytokine Release Syndrome (CRS): A systemic inflammatory response that can range from mild to life-threatening.

  • Neurotoxicity: Including confusion, seizures, and severe encephalopathy.

Conclusion:

CAR-T cell therapies represent a significant advancement in cancer treatment, offering hope to patients with previously untreatable or relapsed diseases. The process involves a complex procedure of modifying the patient's own T cells, which then act as “living drugs” to target and kill cancer cells. Both Kymriah and Yescarta have shown promising results in specific hematological malignancies.

However, these therapies also present significant challenges, including the potential for severe or fatal side effects such as CRS and neurotoxicity. The requirement for specialized manufacturing and handling, along with high costs, can limit access to these innovative treatments. Ongoing research is directed at refining the technology, reducing risks, and expanding the application of CAR-T therapies to other types of cancer. The lessons learned from the development and implementation of Kymriah and Yescarta are guiding the next generation of cell-based immunotherapies.

Durvalumab (Imfinzi)

Durvalumab (Imfinzi) is another prominent immunotherapy drug that has been applied in various therapeutic scenarios. Let's break down the details:

History:

Durvalumab was granted approval by the FDA in 2017, adding another option in the rapidly advancing field of immunotherapy, particularly for certain patients with bladder cancer and lung cancer.

Mechanism of Action – Cancer Cells:

Durvalumab acts on the PD-L1 pathway, having effects including:

  • PD-L1 Blockade: By binding to PD-L1, Durvalumab prevents it from interacting with the PD-1 receptor on T cells.

  • Enhancing Immune Response: This action keeps T cells activated, allowing them to target and attack cancer cells.

  • Restoring Immune Surveillance: It may help restore the ability of the immune system to recognize and destroy cancer cells that have exploited the PD-1/PD-L1 pathway to evade immune detection.

Use:

Durvalumab has found applications in various cancer types:

  • Urothelial Carcinoma: Particularly for patients with disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment.

  • Non-Small Cell Lung Cancer (NSCLC): Approved for the treatment of unresectable Stage III NSCLC, following chemoradiation therapy, showing no disease progression.

Chemistry:

Durvalumab is a human monoclonal antibody that targets the protein PD-L1 (programmed death-ligand 1).

Mechanism of Action – Healthy Cells:

Like other immunotherapies that target the PD-1/PD-L1 pathway, Durvalumab may also affect healthy cells:

  • Immune-Related Adverse Effects: These can include inflammation of the lungs (pneumonitis), liver (hepatitis), colon (colitis), hormonal glands (endocrinopathies), skin (dermatitis), and more.

  • Severe Side Effects: Rare but severe immune-related adverse effects may occur and require careful management, possibly involving immunosuppressive medications.

Conclusion:

Durvalumab has added to the arsenal of immunotherapies targeting the PD-1/PD-L1 pathway, providing options for patients with specific types of cancer like urothelial carcinoma and NSCLC. By selectively targeting PD-L1, Durvalumab has enabled new strategies that enhance the immune response against tumors, although it also comes with a unique spectrum of immune-related side effects. These side effects, while manageable with careful monitoring and intervention, represent an ongoing challenge and area of study. Durvalumab's role in cancer treatment continues to evolve, with ongoing trials examining its effectiveness in various combinations, settings, and cancer types, reflecting the dynamic nature of immunotherapy research.

Sipuleucel-T (Provenge) is a distinctive immunotherapy used to treat certain cases of prostate cancer. Let’s delve into the details of this unique therapy:

Sipuleucel-T (Provenge)

History:

Sipuleucel-T was approved by the FDA in 2010, making it one of the first cancer immunotherapies to receive regulatory approval. It was a significant milestone in the field of immunotherapy, offering a new treatment option for men with metastatic castration-resistant prostate cancer (mCRPC).

Mechanism of Action – Cancer Cells:

Sipuleucel-T works by activating the patient's immune system against prostate cancer cells:

  • Activation of Immune Cells: Patients' immune cells are collected, exposed to PA2024, and then reinfused into the patient. The GM-CSF portion helps the cells to mature and present the antigen more effectively.

  • Targeting Prostate Cancer: By presenting the PAP antigen, which is expressed in prostate cancer cells, the activated immune cells can stimulate a broader immune response against the tumor.

Use:

Sipuleucel-T is indicated for the treatment of asymptomatic or minimally symptomatic mCRPC.

Chemistry:

Sipuleucel-T is a cellular immunotherapy, meaning it's made from the patient's own immune cells. It consists of autologous peripheral blood mononuclear cells (including antigen-presenting cells) activated with a recombinant protein known as PA2024, which consists of prostatic acid phosphatase (PAP) linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).

Mechanism of Action – Healthy Cells:

Since Sipuleucel-T is specifically designed to target a prostate cancer antigen, its effects on healthy cells are generally limited:

  • Mild Side Effects: Common side effects are typically mild to moderate and can include chills, fever, fatigue, nausea, and headache.

  • Infusion Reactions: Some patients may experience reactions related to the infusion process, which can be managed with standard supportive care.

Conclusion:

Sipuleucel-T represents a unique approach to cancer immunotherapy, being one of the first cellular therapies approved for cancer treatment. By utilizing the patient's own immune cells and activating them with a specific prostate cancer antigen, it offers a personalized treatment strategy for men with mCRPC. Unlike some other immunotherapies, Sipuleucel-T's side effect profile is relatively mild, reflecting its targeted approach. Its approval set the stage for subsequent advances in cellular immunotherapy, such as CAR-T cell therapies, demonstrating the potential for using the immune system as a potent weapon against cancer. Ongoing research may further refine and expand the application of Sipuleucel-T and similar approaches in prostate cancer and other malignancies.

Avelumab (Bavencio)

Avelumab, marketed under the brand name Bavencio, is another notable immunotherapy agent used in the treatment of cancer. Here's a comprehensive look:

History:

Avelumab was approved by the FDA in 2017. This made it the first fully human anti-PD-L1 monoclonal antibody to be approved, providing new options for patients with specific cancers.

Mechanism of Action – Cancer Cells:

Avelumab works by interfering with the interaction between PD-L1 and its receptors (PD-1 and B7.1):

  • Blocking PD-L1: Avelumab binds to PD-L1, preventing it from interacting with PD-1 and B7.1 receptors on T cells.

  • Enhancing Immune Response: By inhibiting this pathway, Avelumab helps to restore the T cells' ability to detect and attack cancer cells.

  • Inducing Anti-Tumor Immunity: It can promote an adaptive immune response against tumors expressing PD-L1, thereby having a broader effect on the tumor environment.

Use:

Avelumab has been approved for various indications, including:

  • Merkel Cell Carcinoma (MCC): For adult and pediatric patients 12 years and older with metastatic MCC.

  • Urothelial Carcinoma: For patients with locally advanced or metastatic urothelial carcinoma with progression during or after platinum-containing chemotherapy.

  • Renal Cell Carcinoma (RCC): In combination with axitinib, for first-line treatment of advanced RCC.

Chemistry:

Avelumab is a human IgG1 monoclonal antibody that targets the PD-L1 protein, which is a component of a critical immune checkpoint pathway.

Mechanism of Action – Healthy Cells:

As with other immunotherapies targeting the PD-1/PD-L1 pathway, Avelumab may affect normal tissues:

  • Immune-Related Adverse Effects: These can include immune-mediated pneumonitis, hepatitis, colitis, endocrinopathies, nephritis, and other inflammatory conditions.

  • Infusion-Related Reactions: Some patients may experience reactions during or following the infusion, which generally can be managed with appropriate interventions.

Conclusion:

Avelumab represents an essential development in the field of immunotherapy, particularly for patients with certain hard-to-treat cancers like MCC. By selectively targeting the PD-L1 protein, it leverages the body's own immune system to recognize and destroy cancer cells. However, the activation of the immune system also presents challenges in terms of managing immune-related side effects. Ongoing clinical trials continue to investigate the potential of Avelumab in various combinations and settings, reflecting the evolving landscape of cancer immunotherapy and the pursuit of more effective, personalized treatments. The success of Avelumab adds to the growing body of evidence supporting the role of immune checkpoint inhibitors in cancer therapy, expanding options for patients and informing future research.

History:

Cemiplimab was approved by the FDA in 2018, adding to the growing list of immune checkpoint inhibitors in the field of cancer treatment. It was the first drug approved specifically for advanced cutaneous squamous cell carcinoma (CSCC).

Cemiplimab (Libtayo)

Cemiplimab, marketed under the brand name Libtayo, is an immunotherapy used to treat certain types of cancer. Here's an in-depth look at this therapy:

Mechanism of Action – Cancer Cells:

Cemiplimab's primary mechanism of action includes:

  • PD-1 Blockade: By binding to PD-1, Cemiplimab prevents this receptor from interacting with its ligands, PD-L1 and PD-L2.

  • Reactivating T cells: This blockade enables the activation of T cells, leading to increased immune responses against cancer cells expressing PD-L1.

  • Enhancing Anti-Tumor Response: By boosting the body's ability to target cancer cells, Cemiplimab may enhance overall anti-tumor immunity.

Use:

Cemiplimab has been approved for the following indications:

  • Cutaneous Squamous Cell Carcinoma (CSCC): For the treatment of patients with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation.

  • Non-Small Cell Lung Cancer (NSCLC): More recently, it has been used in first-line treatment for patients with NSCLC expressing PD-L1, expanding its therapeutic scope.

Chemistry:

Cemiplimab is a human monoclonal antibody that targets the PD-1 receptor. It's part of the class of drugs known as immune checkpoint inhibitors.

Mechanism of Action – Healthy Cells:

As with other drugs targeting the PD-1 pathway, Cemiplimab can have effects on normal tissues:

  • Immune-Related Adverse Effects: Including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions. These result from the generalized activation of the immune system.

  • Infusion-Related Reactions: Which can be managed with appropriate medical interventions.

Conclusion:

Cemiplimab represents a vital addition to the options available for patients with advanced CSCC, a cancer for which there were previously limited treatment choices. Its success in treating this specific type of skin cancer exemplifies the promise of personalized cancer immunotherapy. By selectively targeting the PD-1 pathway, it provides a mechanism to unleash the body's immune response against cancer cells. However, this can also lead to immune-related side effects that require careful management. Ongoing studies continue to explore the full potential of Cemiplimab in various cancers and treatment settings, reflecting the dynamic and patient-centric approach of modern oncology. The ongoing success of Cemiplimab and other immune checkpoint inhibitors underscores the importance of understanding the complex interactions between the immune system and cancer, driving further innovations in cancer treatment.

Tisagenlecleucel, marketed as Kymriah, is a remarkable advancement in the field of cancer treatment, particularly as one of the first FDA-approved chimeric antigen receptor T-cell (CAR-T) therapies. Here's a comprehensive exploration of this innovative therapy:

Tisagenlecleucel (Kymriah)

History:

Tisagenlecleucel was approved by the FDA in 2017, marking a significant milestone in cancer treatment. It was the first CAR-T cell therapy approved, heralding a new era of personalized cancer immunotherapy.

Mechanism of Action – Cancer Cells:

The primary mechanism of action of Tisagenlecleucel includes:

  • Targeting CD19: The CAR expressed on the modified T cells specifically binds to the CD19 antigen, found on B-cell leukemias and lymphomas.

  • Activating T Cells: Once bound to CD19, the CAR-T cells become activated and kill the target cells.

  • Inducing Immune Memory: Modified T cells may persist in the body, providing potential long-term immune surveillance against the cancer.

Use:

Tisagenlecleucel has been approved for:

  • Pediatric and Young Adult Acute Lymphoblastic Leukemia (ALL): Specifically for refractory ALL or ALL that has relapsed at least twice.

  • Adult Relapsed or Refractory Large B-Cell Lymphoma: Including diffuse large B-cell lymphoma (DLBCL) and other related subtypes, after two or more lines of systemic therapy.

Chemistry:

Tisagenlecleucel is a CAR-T cell therapy, which means it's made from a patient's own T cells that have been genetically modified to express a specific chimeric antigen receptor (CAR) that targets the CD19 antigen, a protein found on B cells.

Mechanism of Action – Healthy Cells:

The targeting of CD19 can also affect healthy B cells:

  • B-Cell Aplasia: Since CD19 is present on healthy B cells, the therapy can lead to their depletion, causing a condition known as B-cell aplasia. This requires careful monitoring and management.

  • Cytokine Release Syndrome (CRS): A potentially severe side effect, CRS results from the rapid activation and expansion of CAR-T cells, leading to high levels of inflammatory cytokines.

  • Neurologic Events: Some patients may experience neurological side effects, the cause of which is still not entirely understood.

Conclusion:

Tisagenlecleucel represents a transformative approach in the treatment of specific B-cell malignancies, particularly for patients who have exhausted other treatment options. By utilizing a patient's own T cells and reengineering them to target CD19, this therapy has shown remarkable success in clinical trials. However, it also comes with unique challenges, such as CRS and neurological events, requiring specialized care and facilities capable of managing these complex side effects. The success of Tisagenlecleucel has paved the way for further research into CAR-T cell therapies, leading to the development of additional products and ongoing trials exploring their use in various cancers. The emergence of CAR-T cell therapy exemplifies the cutting-edge intersection of genetic engineering, immunology, and oncology, offering hope for many patients with previously untreatable cancers.