What Is Interleukin-2 (IL-2) Cancer Treatment?

IL-2 treatment doesn’t attack cancer directly. It amplifies one of the body’s own immune signals so the immune system does the fighting. As one of the first immunotherapies, it has been used against advanced melanoma and kidney cancer since the 1990s.¹ It works for a minority of patients, but when it works fully, the result can be a remission measured in years rather than months.²

How IL-2 Turns Up the Immune System

Your body already makes IL-2. It was first discovered as a growth factor for T cells, the white blood cells that recognize and kill infected or abnormal cells.³ When T cells are activated, IL-2 helps them multiply into large numbers.⁴ It also makes killer T cells and natural killer cells better at destroying their targets.⁵ The drug version is a lab-made copy of this signal, given in doses far above what the body makes.

A tumor is made of the patient’s own altered cells, so the immune system often fails to treat it as a threat. IL-2 is meant to push T cells past that indifference. In animal research, IL-2 strengthened an immune response against the tumor that the body had already begun, and that is when tumors shrank.⁶ The goal is a much larger army of cancer-recognizing cells than the body would make alone, which is why the dose is so high. Because IL-2 never touches the cancer itself, results depend on the patient’s own immune cells. That is why responses can be slow and can last long after treatment ends.

The same signal also feeds the immune system’s brakes. IL-2 keeps alive a type of immune cell that calms immune reactions down.⁷ These brake cells carry a receptor part that grabs IL-2 especially tightly.⁸ At high doses IL-2 mainly drives attacking cells, while at low doses it mainly boosts brake cells.⁹

This tug-of-war partly limits how well standard IL-2 works. Many newer IL-2 drugs are designed to avoid the brake cells, and they come up later in this article.

Who Gets High-Dose IL-2 and How It Is Given

Aldesleukin (Proleukin) was approved for kidney cancer that has spread in 1992 and for melanoma that has spread in 1998.¹⁰ That was before targeted drugs and checkpoint-inhibitor immunotherapy existed, so today high-dose IL-2 is one option among several.¹¹ It is also given alongside some cell therapies made from a patient’s own tumor-fighting T cells, to help those cells multiply.¹² CAR-T cell therapy does not need added IL-2.¹³

The drug is given through a vein, usually every 8 hours at the highest dose the person can tolerate, as an inpatient.¹⁴ A typical hospital stay for a course lasts around 4 to 5 days.¹⁵ Doses are stopped or skipped when side effects become too strong, so people end up receiving different numbers of doses.

Because the treatment strains the heart, lungs and kidneys, candidates generally need good overall health and organ function. Doctors typically check heart and lung function before starting, and people with serious heart disease are often not good candidates. Ask your oncologist which tests they require.

Each stay is followed by a rest period of about a week or so before a second stay, and the pair of stays makes up a course. Scans afterward show whether a further course makes sense. It helps to plan for time off work and a caregiver for the weeks involved.

How Often IL-2 Works and How Long Results Last

In recent melanoma patients, all visible cancer vanished in 5% (a complete response), and tumors shrank substantially in another 10%.¹⁶ For kidney cancer, the numbers were 6% and 9%.¹⁷ In both cancers, about 6 in 10 patients saw their cancer keep growing despite treatment, and about 1 in 5 had cancer that held steady without growing.¹⁸

Tumor shrinkage is not the same as cure, while a complete response (all visible cancer gone) that lasts years may be. In a large group of patients, about 8 in 10 of those with a complete response were still cancer-free 3 to over 12 years later.¹⁹ A small group of people treated only with IL-2 have gone 5 years or more without their cancer returning.²⁰ In recent patients, half of those with melanoma lived longer than about 20 months, and half of those with kidney cancer lived longer than about 41 months.²¹

Newer checkpoint immunotherapies help more people and are easier to tolerate, so many people try them first. IL-2 is now often considered after or alongside them, and it can still be offered when other options have failed.

Doctors judge response by scans taken some weeks after treatment, not by how the patient feels in the hospital. Shrinkage can continue for a while after the last dose, so an early scan may not show the final result. How sick you feel during treatment does not show whether the drug is working.

There are a few clues about who responds. In one hospital’s experience, people who benefited more often had a larger drop in platelets during treatment, and they more often developed autoimmune side effects, such as thyroid or skin changes.²² These clues show up only during treatment, so no test yet predicts beforehand who will respond.

Side Effects and What Treatment Feels Like

High-dose IL-2 makes small blood vessels leaky so fluid seeps into tissues, a problem called capillary leak.²³ Blood pressure then drops, and many patients need drugs to raise it.²⁴ In one intensive care group, about 8 in 10 had fever and 7 in 10 had a fast heartbeat.²⁵ About 7 in 10 developed severe capillary leak in that group, though only 4 of 14 needed blood pressure drugs, typically for about 8 hours.²⁶

Day to day, the fluid shows up as quick weight gain and a puffy look, particularly in the face, hands and feet. Fluid can also collect in the lungs, which is one reason breathing and oxygen levels are watched closely. Once doses stop, the vessels tighten again and the body gets rid of the extra fluid, often through a lot of urination.

Fever and shaking chills often start within hours of a dose, as though you were coming down with a bad flu. These reactions come in waves around each dose, which makes the pattern predictable for the team. Nurses can give medicines to ease fever, chills and aches, so speak up rather than tough it out. Many people also get nausea, diarrhea and itchy red skin. Kidney function often dips temporarily and is checked daily, and fatigue can last weeks after going home.

Patients and families often describe confusion, hallucinations and sleeplessness as the most alarming effects.²⁷ Reaction time, memory and attention can drop during the infusions.²⁸ For most people, thinking returns to normal within 10 days of the last dose.²⁹ Families should know beforehand that a loved one may not recognize them for a time.

Caregivers can help by staying with the patient as much as the unit allows, since familiar faces help with confusion. Tell nurses quickly about any new confusion or odd behavior.

Because IL-2 leaves the body within an hour or so of each dose, side effects usually ease quickly once doses stop.³⁰ In a registry of 362 recent patients, no one died from the treatment.³¹

Why the Hospital You Choose Matters

Experts say high-dose IL-2 needs trained staff, heart and oxygen monitoring, drugs to raise blood pressure, and a low number of patients per nurse.³² It may be given in an intensive care unit, a step-down unit, or a specialized cancer ward.³³ Some cancer centers give it on a general cancer ward with monitoring available when needed.³⁴

Across nearly 30,000 US patients, 0.4% died during their IL-2 hospital stay.³⁵ The death rate was 0.13% at high-volume hospitals and 1.31% at hospitals giving 20 or fewer courses a year.³⁶ Low-volume hospitals also had longer stays and higher charges, about $93,000 versus $62,000.³⁷ So it is worth asking how many IL-2 courses a hospital gives each year, and considering travel to a high-volume center.

These figures describe hospital groups across the country, so they cannot predict what will happen to one person. Sicker patients may also be treated at certain hospitals, so not all of the difference is necessarily down to the hospital itself.

Useful questions for a treatment center:

How many patients do you treat with high-dose IL-2 each year?
Which unit will I stay in, and who manages side effects overnight?
How do you handle low blood pressure and confusion?
What insurance approval and costs should I expect?

Newer IL-2 Drugs and Combinations

Some new IL-2 drugs are designed to skip the receptor part that brake cells grab, so they favor attacking cells.³⁸ One such design boosted attacking cells far more than brake cells in early research.³⁹ Attaching a coating called PEG makes IL-2 last 10 to 20 times longer in the blood.⁴⁰ Longer-lasting versions could be given less often than every 8 hours.⁴¹ A drug that lingers is also harder to stop if side effects get bad.

Another approach is delivering IL-2 to the tumor. Linking IL-2 to an antibody that homes in on tumors can deliver it where needed and lower body-wide inflammation.⁴² Injecting IL-2 straight into tumors can work well against the injected tumors at lower doses, without the severe body-wide side effects.⁴³ In melanoma with skin or under-skin tumors, weekly injections of one such drug cleared all treated tumors in 1 in 4 patients, most for 2 years or more.⁴⁴

Direct injection only works when the tumor can be reached, such as on or just beneath the skin. It can help the tumors that were treated, but it doesn’t reach hidden cancer elsewhere unless the immune response spreads. Antibody-linked versions try to solve this by traveling through the blood and gathering at tumors anywhere.

Adding IL-2 to two checkpoint drugs reawakened immune cells in patient tumor samples that had resisted those drugs.⁴⁵ In mice, that triple combination cured almost twice as many as checkpoint drugs alone.⁴⁶ These results come from lab and animal studies, not proof of benefit in patients.

For now, high-dose aldesleukin remains the approved IL-2 cancer drug. Some engineered versions have disappointed in later trials, so early promise is not a guarantee. If standard options are limited, ask your oncologist about clinical trials of newer IL-2 drugs. Trials are often listed on ClinicalTrials.gov and run at major cancer centers.

Low-Dose IL-2 Is a Different Treatment

Low doses of IL-2 expand and activate the brake cells, which can help control autoimmune diseases and inflammation.⁴⁷ In a trial in people with lupus, low-dose IL-2 raised brake-cell numbers, most at the higher test dose.⁴⁸ Reports about low-dose IL-2 for autoimmune disease do not describe cancer treatment.

Low-dose IL-2 is generally given as small injections, often in cycles, rather than as hospital infusions. It is mostly being studied in trials, so it is not a standard treatment for lupus or most other autoimmune conditions.