Can Il-2 be used to treat cancer?
Apr 25, 2016 · Interleukin-2 (IL-2) is one of the key cytokines with pleiotropic effects on immune system. It has been approved for the treatment of metastatic renal cell carcinoma and metastatic melanoma. Recent progress has been made in our understanding of IL-2 in regulating lymphocytes that has led to exciting new directions for cancer immunotherapy.
How does interleukin-2 (IL-2) affect lymphocytes?
IL-2 is a synthetic form of interleukin-2, a protein that the body produces naturally. Interleukin-2 was discovered more than 20 years ago. The U.S. Food and Drug Administration approved it in its synthetic form for treatment against cancer in 1992.
When was IL-2 approved for melanoma treatment?
The growth of large numbers of tumor-infiltrating lymphocytes with in vitro anti-cancer activity in IL-2 has led to the development of cell transfer therapies that are highly effective in patients with melanoma. The genetic modification of T cells with genes encoding αβ TCRs or chimeric Ag receptors and the administration of these cells after expansion in IL-2 have extended effective …
What is Interleukin-2 immune therapy?
IL-2 works as a systemic treatment to: Shrink melanoma tumors Kill melanoma cells
What is IL-2 chemo?
Aldesleukin is an immunotherpay drug. It is also known as interleukin 2 (IL-2) or by its brand name Proleukin. It is a treatment for kidney cancer that has spread to another part of the body (advanced kidney cancer). It is also used in clinical trials for other types of cancer.
What are the side effects of interleukin-2?
Side effects of IL-2 can include flu-like symptoms such as chills, fever, fatigue, and confusion. Some have nausea, vomiting, or diarrhea. Many people develop low blood pressure, which can be treated with other medicines.Dec 27, 2019
What does interleukin-2 do in cancer?
It increases the growth and activity of other T lymphocytes and B lymphocytes, and affects the development of the immune system. Aldesleukin (interleukin-2 made in the laboratory) is being used as a biological response modifier to boost the immune system in cancer therapy.
Why is IL-2 toxic?
The most common manifestation of IL-2 toxicity is capillary leak syndrome, resulting in a hypovolemic state and fluid accumulation in the extravascular space. Capillary leak syndrome can contribute significantly to development of oliguria, ischemia, and confusion.
What are the benefits of interleukins?
Interleukins regulate cell growth, differentiation, and motility. They are particularly important in stimulating immune responses, such as inflammation. Interleukins are a subset of a larger group of cellular messenger molecules called cytokines, which are modulators of cellular behaviour.
What is a cytokine storm?
Cytokine storm syndrome refers to a group of related medical conditions in which the immune system is producing too many inflammatory signals, sometimes leading to organ failure and death.Nov 4, 2021
What is interleukin treatment?
Immunotherapy is cancer treatment that stimulates the body's immune system to fight cancer, such as melanoma. Interleukin-2 is systemic therapy, which means that the treatment reaches all parts of your body through the bloodstream.
Is IL-2 an immunotherapy?
IL-2 was an early candidate for cancer immunotherapy and was approved for the treatment of metastatic renal cell carcinoma (1992) and later for metastatic melanoma (1998) by FDA.
What is the name of the doctor that treated cancer patients with IL-2 immunotherapy?
Theodore Logan, M.D., associate professor of clinical medicine at the IU School of Medicine and a physician scientist at the IU Simon Cancer Center, is an immunotherapy expert. He specializes in interleukin-2, a type of cytokine.Jun 20, 2016
Is Aldesleukin chemotherapy?
Until 2011, there were only two drugs approved by the US Food and Drug Administration (FDA) including dacarbazine, a chemotherapeutic agent, and aldesleukin, a cytokine therapy, also known as high-dose interleukin (IL)-2.Apr 7, 2015
What are cytokines made of?
Cytokines are a large group of proteins, peptides or glycoproteins that are secreted by specific cells of immune system. Cytokines are a category of signaling molecules that mediate and regulate immunity, inflammation and hematopoiesis.
What medications cause cytokine release syndrome?
CRS can be triggered by infections or be associated with drugs such as monoclonal antibodies (e.g., rituximab), conventional chemotherapy, and immunotherapies with chimeric antigen receptor T (CAR T) cells (Shimabukuro-Vornhagen et al., 2018).May 4, 2020
What is IL-2?
This helps the body fight cancer. IL-2 is a synthetic form of interleukin-2, a protein that the body produces naturally. Interleukin-2 was discovered more than 20 years ago. The U.S. Food and Drug Administration approved it in its synthetic form for treatment against cancer in 1992.
What is IL-2 used for?
What IL-2 Is Used For: Cancers treated with IL-2 include renal cell (kidney) and melanoma, a skin cancer. Note: If a drug has been approved for one use, physicians sometimes elect to use this same drug for other problems if they believe it may be helpful.
What is the trade name for Aldesleukin?
Proleukin ® is the trade name for the generic drug name Aldesleukin. IL-2 and Interleukin-2 are other names for Aldesleukin. In some cases, health care professionals may use the trade name Proleukin ® or other names IL-2 and Interleukin-2 when referring to the generic drug name Aldesleukin.
How often is IL-2 given?
The high-dose regimen involves giving the drug intravenously (into a vein) every eight hours, as tolerated, for up to 15 doses.
How many episodes of vomiting in 24 hours?
Nausea that interferes with eating and is not relieved by medications prescribed by your doctor. Vomiting (more than 4 to 5 episodes within a 24-hour period).
What are the side effects of IL-2?
The following are common (occurring in greater than 30%) side effects for patients taking IL-2: Fever and chills or flu-like symptoms. The severity decreases over time, particularly in low-dose regimens. Generalized flushing (redness) of the face and body, or skin rash.
How to avoid infection?
Wash your hands often . You may be at risk of infection so try to avoid crowds or people with colds, and report fever or any other signs of infection immediately to your healthcare provider. Maintain good nutrition. If you experience symptoms or side effects, be sure to discuss them with your health care team.
What is IL-2 in immunotherapy?
Interleukin-2 (IL-2), also known as aldesleukin or PROLEUKIN®, is an immunotherapy treatment for people with advanced and metastatic melanoma. IL-2 is a naturally occurring protein that is produced by a specific type of white blood cell, a T lymphocyte.
What is IL-2 used for?
IL-2 used for melanoma therapy is manufactured into a product called aldesleukin, a drug used to boost the immune system to fight cancer cells.
What is interleukin 2?
Interleukin-2 (IL-2, Aldesleukin, PROLEUKIN®) Immunotherapy is cancer treatment that stimulates the body’s immune system to fight cancer, such as melanoma . Interleukin-2 is systemic therapy, which means that the treatment reaches all parts of your body through the bloodstream. Systemic cancer treatments fight advanced and metastatic cancers, ...
How does IL-2 work?
IL-2 works as a systemic treatment to: Shrink melanoma tumors. Kill melanoma cells. As an immunotherapy, IL-2 stimulates your immune system, which has an immunological “memory.”. That means that IL-2 may help your immune system continue to attack melanoma cells even after your treatment ends. Physicians now have extensive experience ...
When was IL-2 approved?
The U.S. Food and Drug Administration (FDA) approved IL-2 in 1998 to treat patients with stage IV (metastatic) melanoma. In stage IV melanoma, cancer cells have spread to organs and other parts of the body.
What is the treatment for metastatic cancer?
Systemic cancer treatments fight advanced and metastatic cancers, which have spread to other parts of the body. Interleukin-2 is an immunotherapy that activates the immune system to kill melanoma cells and shrink tumors wherever they develop in the body.
Is IL-2 a serious drug?
Melanoma treatments, like IL-2, have side effects, which can sometimes be serious. Patients should talk with their physician to learn more about the side effects of IL-2 and other melanoma treatment options.
What is IL-2 in cancer?
Interleukin-2 (IL-2) is one of the key cytokines with pleiotropic effects on immune system. It has been approved for the treatment of metastatic renal cell carcinoma and metastatic melanoma. Recent progress has been made in our understanding of IL-2 in regulating lymphocytes that has led to exciting new directions for cancer immunotherapy.
What is IL-2?
Interleukin-2 (IL-2) is one of the key cytokines with pleiotropic effects on immune system. It has been approved for the treatment of metastatic renal cell carcinoma and metastatic melanoma.
What is IL-2 in medicine?
Interleukin-2 (IL-2) is a potent human protein that can activate and also dampen the body’s immune response . Nearly 30 years after the US Food and Drug Administration first approved IL-2 to treat melanoma and kidney cancer, a host of pharma and biotech companies are racing to the clinic with engineered versions of the protein that they hope will be safer and more precise than those in use today. Others are trying to harness IL-2’s immune-suppressive power to treat autoimmune diseases.
What is the purpose of IL-2?
Several companies are trying to engineer the interleukin-2 (IL-2) protein to steer its activity toward T cells that kill cancer or T cells that block autoimmune responses. Here are some examples.
What is the drug that stimulates the immune system?
But there was a drug called Proleukin that, for better or worse, gripped his attention. Proleukin, also called aldesleukin, was a therapeutic version of interleukin-2 (IL-2), a small human protein called a cytokine that could attach to specific kinds of immune cells and stimulate them to grow and divide.
Does IL-2 stimulate T cells?
Natural IL-2 stimulates both effector and regulatory T cells to multiply, providing an army that allows the immune system to do its job, but with checks and balances. Indeed, providing checks and balances seems to be IL-2’s most fundamental task, Spangler says.
What is the IL-2 antibody?
Now, Umaña says, Roche is working on an IL-2-antibody construct that attaches to two points on the same T cell: the β and γ parts of the IL-2 receptor as one point, and PD-1, an immune-regulating protein that many cancer immunotherapies attempt to override to make T cells more effective at killing, as the other.
Can IL-2 stimulate effector cells?
What this means for IL-2 as a therapy is that building an IL-2-like compound that stimulates mainly effector cells to grow could spur a potent anticancer immune response, Spangler says. And building an artificial IL-2 to preferentially stimulate regulatory cells could create something that mainly fights autoimmunity.
What is NL 201?
NL-201, Neoleukin’s IL-2-mimicking compound, came out of the Institute for Protein Design at the University of Washington. Carl Walkey, an executive at Neoleukin who was previously at the institute, says the team used computational biology to envision what an ideal IL-2 would look like as a cancer treatment.
What are the side effects of IL-2?
Side effects of IL-2 can include flu-like symptoms such as chills, fever, fatigue, and confusion. Some have nausea, vomiting, or diarrhea. Many people develop low blood pressure, which can be treated with other medicines.
What is the purpose of interleukin 2?
Interleukins. Interleukins are a group of cytokines that act as chemical signals between white blood cells. Interleukin-2 (IL-2) helps immune system cells grow and divide more quickly. A man-made version of IL-2 is approved to treat advanced kidney cancer and metastatic melanoma. IL-2 can be used as a single drug treatment for these cancers, ...
What are the different types of interferons?
Interferons are chemicals that help the body resist virus infections and cancers. The types of interferon (IFN) are named after the first 3 letters of the Greek alphabet: 1 IFN-alfa 2 IFN-beta 3 IFN-gamma
What is a chemokine?
A chemokine can make immune cells move toward a target. There are different kinds of chemokines, including interleukins, interferons, tumor necrosis factors, and growth factors. Some cytokines can be made in a lab and are used to treat cancer. Some are used to help prevent or manage chemotherapy side effects.
Does interferon cause fatigue?
Low white blood cell counts (which increase the risk of infection) Skin rashes. Thinning hair. These side effects can be severe and can make treatment with interferon hard for many people to tolerate. Most side effects don’t last long after the treatment stops, but fatigue can last longer.
What are the effects of IL-2?
Common neurologic adverse events associated with IL-2 are confusion, somnolence, disorientation, anxiety, and dizziness. [1,21] Patients receiving IL-2 may also experience altered sleep patterns; behavioral changes, such as agitation and combativeness; vivid dreams; paranoia; or emotional lability. [8] Many of these symptoms may be caused by medications used to treat other IL-2-induced symptoms (eg, meperidine for chills in an opiate-naive patient, phenothiazine for nausea).
What are the toxicities of IL-2?
IL-2 administration causes a broad range of cardiopulmonary toxicities, with hypotension, tachycardia, and dyspnea being the most common. [1] Hypotension and tachycardia often develop within 2 hours of the first dose, progressing in severity as therapy continues. [8] Hypotension usually reverses within 48 hours after IL-2 discontinuation. [8] The results of early clinical trials show that high-dose IL-2 produced grade 3/4 hypotension requiring vasopressor support in up to 81% of patients. [5] A more recent study shows that only 31% of patients required vasopressor support.
How does IL-2 cause capillary leak syndrome?
IL-2 toxicity is mediated through lymphoid infiltration, a well-described capillary leak syndrome, and the local effects of secondary cytokines. [8] The complex mechanism of action whereby IL-2 induces capillary leak syndrome is postulated to involve a series of steps, including induction of circulating cytokines, such as tumor necrosis factor-alfa (TNF-a) and other interleukins; generation of complement-activation products; neutrophil activation; and activation of endothelial-cell antigens. [8] After IL-2 administration, induced cytokines are released, leading to increased capillary permeability and decreased vascular resistance, which results in a shift of fluid from the bloodstream into the extravascular space. This fluid shift ultimately leads to a hypovolemic state and excessive fluid in the extravascular space. Capillary leak syndrome-associated fluid accumulation in the extravascular spaces may manifest as generalized edema, weight gain, pulmonary congestion, pleural effusions, and ascites. [8] Capillary leak syndrome-associated hypovolemia may cause decreased blood flow to the kidneys, gut, heart, and brain, resulting in oliguria, ischemia, and confusion. Usually, capillary leak syndrome affects more than one organ system simultaneously, contributing to the toxicity often observed in patients receiving high-dose IL-2. The release of cytokines after IL-2 administration has also been implicated as the cause of flu-like symptoms, such as fever, chills, myalgias, and arthralgias.
Where does IL-2 infection occur?
Most IL-2-related infections occur in the urinary tract or at the site of venous catheter placement , with Staphylococcus aureus and S epidermidis being the most commonly isolated pathogens. [8,16] Patients receiving IL-2 therapy are also at risk of infection, because IL-2 causes a reversible and profound defect in neutrophil chemotaxis. [16] Patients with persistent fevers despite routine administration of antipyretics and those with signs and symptoms of infection should be promptly assessed, undergo testing to identify the causative organism, receive empiric antibiotic therapy, and, if appropriate, have the indwelling catheter removed. IL-2 therapy should be withheld until the symptoms of infection resolve and culture results are negative.
What are the hematologic abnormalities of IL-2?
Hematologic abnormalities, including anemia, leukopenia, and thrombocytopenia, are common during IL-2 therapy, but are rarely severe or dose limiting. Baseline and routine (at least daily) assessment of complete blood counts are used to identify changes in hematologic parameters that would require treatment. The results of one large study showed that 14% of patients receiving high-dose IL-2 developed anemia requiring red blood cell transfusions. [25] Severe leukopenia occurred in only 1.5% of patients and was not associated with an increased risk of infection; however, alterations in neutrophil function caused by a profound chemotactic defect are common and associated with the development of infection. [16]
How long does it take for a chill to develop after taking IL-2?
Chills, fever, and malaise are among the most common and predictable adverse events associated with high-dose IL-2. Typically, chills develop within 1 to 2 hours of the first or second dose and are treated with repeated doses of meperidine and warm blankets.
Is IL-2 toxic to the body?
High-dose IL-2 efficacy and toxicity are dose- and schedule-dependent. [8] High-dose IL-2 administered as an IV bolus is more toxic than low-dose IL-2 administered as either an IV bolus or subcutaneously. [9] Continuous IV infusion of high-dose IL-2 is more toxic than bolus administration of the same doses. [8] IL-2-related toxicities are generally reversible after therapy discontinuation, resolving within 2 to 3 days of therapy completion. [8] Long-term sequelae due to IL-2 toxicity are rare, but may occur, especially in patients whose toxicities are not managed appropriately.