The immune system, also known as the body’s defense force, is truly remarkable. It identifies and destroys threats, including malignant (cancerous) cells. Among the many components of this system, white blood cells (WBCs) take the lead in combating disease-causing microbes and cells.
A subset of WBCs called lymphocytes has two types of immune cells:
- T cells can attack and kill infected or abnormal cells
- B cells make antibodies that bind to foreign targets for elimination.
These immune cells are in charge of recognizing and eliminating diseases, including cancer. However, tumors are notorious for evading detection by exploiting the immune checkpoints on the surface of T and B cells. These checkpoints (a type of protein) switch off immune attacks to protect healthy tissue. Cancer cells hijack these signals to hide from the immune system.
Immunotherapy boosts and strengthens the immune system so it’s better at eradicating cancer. In practice, these treatments enlist the body’s natural defenses to attack malignant cells, either by stimulating immune cells or by adding lab-designed proteins (antibodies or receptors) that target tumors.
The result? Nothing short of extraordinary. In many cases, immunotherapy shrinks tumors even when conventional treatments have failed.
Types of Immunotherapy: How Doctors “Train” the Immune System to Fight Cancer
Each one of the following harnesses the immune system differently:
1. Monoclonal Antibodies
Monoclonal antibodies (MoAbs) are lab-made proteins that act similarly to human antibodies in the immune system. Some antibodies work by blocking the signals that malignant cells need to grow; others flag the cancer cells so that the patient’s immune cells can attack them.
Common Types of Monoclonal Antibodies
Rituximab is a form of monoclonal antibody used to treat certain blood cancers like non-Hodgkin lymphoma. It binds to a protein on the surface of lymphoma cells. Once attached, the immune system recognizes those cells as abnormal and removes them.
Trastuzumab is another example, which oncologists use to address breast cancers that produce too much of a protein called HER2. This anti-HER2 drug helps slow or stop all four stages of HER2-positive breast cancer and some HER2-low breast cancers.
Some MoAbs deliver medicine straight to cancer cells. Ado-trastuzumab emtansine (T-DM1) is a leading example, which combines trastuzumab with a low dose of chemotherapy. This way, the drug delivers chemotherapy into the cancer cell instead of wreaking havoc on the whole body.
Side Effects
Because monoclonal antibodies target cancer cells more precisely than standard chemotherapy, patients typically experience fewer side effects. Specifically, about 30–50% of cancer patients experience mild side effects from immunotherapy, while severe side effects happen to less than 5% of people. By comparison, 66.7% experience six or more side effects from chemotherapy, while 97.4% experience at least one side effect from radiation therapy.
2. Immune Checkpoint Inhibitors
Immune checkpoints operate as “brakes” on the immune response. In healthy tissue, they turn off T cells to prevent “autoimmunity,” or when the immune system mistakenly identifies healthy cells, tissues, and organs as foreign invaders. However, tumors exploit these checkpoints to hide from T cells. Checkpoint inhibitor drugs are antibodies that block these brakes and free the T cells to attack cancer.
Common Types of Immune Checkpoint Inhibitors
The first checkpoint approved was ipilimumab, which blocks the inhibitory receptor CTLA-4 on T cells. Since the early 2010s, antibodies blocking PD-1 (nivolumab, pembrolizumab) or its partner PD-L1 (atezolizumab, durvalumab, avelumab) have been approved for many cancers, including but not limited to melanoma, lung, kidney, bladder, head and neck, and Hodgkin lymphoma.
A relatively new addition is relatlimab, which blocks LAG-3 (another checkpoint). In a melanoma trial, nivolumab + relatlimab nearly doubled progression-free survival compared to nivolumab alone (10.1 vs 4.6 months), which convinced the U.S. FDA to approve the combination. Blocking LAG-3 and PD-1 together unleashes an immune response by taking off two brakes.
These drugs train T cells to attack cancer cells by stopping the off-signals that would shut them down. When effective, they can produce dramatic and long-lasting remissions. For instance, in metastatic non-small-cell lung cancer with PD-L1 tumors, checkpoint inhibitors have become standard front-line therapy because they improved survival from 16.3% (chemotherapy) to 31.9% with pembrolizumab. They are also compatible for concomitant use with chemotherapy or targeted therapy.
Side Effects
Checkpoint inhibitors can cause immune-related adverse events (irAEs) because the activated immune system may attack normal organs. Patients may experience inflammation in the form of rashes or dermatitis, colitis (diarrhea), hepatitis (liver enzymes rise), pneumonitis (lung inflammation causing cough or shortness of breath), and endocrinopathies (thyroiditis or adrenalitis causing hormone issues). Mild reactions like fatigue, itchy rash, or thyroid changes are also common.
As for the likelihood of a patient encountering side effects, a 2024 systematic review found that 40% of patients on checkpoint inhibitors experienced some immune-related side effect, and about 20% had a serious (grade 3-4) event. Rates are lower for single-agent PD-1/PD-L1 therapy (~30%) and higher (~46%) when combining multiple immunotherapies.
Managing these side effects may require additional immune-suppressing treatments, and, in some cases, steroids. Patients and healthcare teams must discuss these risks before proceeding with treatment.
Checkpoint inhibitors are most effective when tumors have multiple mutations or contain immune cells. Patients need testing for biomarkers like PD-L1 expression or MSI status to predict whether they will benefit from this type of immunotherapy. However, not every patient responds. For instance, even in MSI-high colorectal cancer, which is highly responsive, studies showed that less than half of patients have long-lasting responses to a single PD-1 drug. Combining checkpoints (PD-1 with CTLA-4 or LAG-3) or adding chemotherapy improves the chances of response in some cancers.
3. Cancer Vaccines
Cancer vaccines come in two general categories:
- Preventive vaccines: These vaccines protect against cancer-causing viruses. The HPV vaccine (Gardasil), for example, defends against human papillomaviruses that cause cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancers. The hepatitis B vaccine, on the other hand, averts chronic infections that can lead to liver cancer. While these vaccines do not treat cancer, they reduce the risk of virus-driven cancers.
- Therapeutic cancer vaccines: Healthcare providers administer these vaccines to people already diagnosed with cancer. They introduce tumor-associated antigens, or patient-specific neoantigens, to activate immune cells. An early example is sipuleucel-T (Provenge) for metastatic prostate cancer. This personalized vaccine uses the patient’s immune cells pulsed with a prostate antigen. It was FDA-approved in 2010 based on a trial showing a modest survival extension in advanced prostate cancer.
More recently, personalized mRNA vaccines have shown promise. For instance, combining pembrolizumab with Moderna’s mRNA-4157 vaccine, which encodes neoantigens from the patient’s tumor, reduced melanoma’s 2-year recurrence risk by 44% compared to pembrolizumab alone. However, such vaccines are expensive (around $100,000 each) and are still seeking approval, but dozens of trials are underway. One review notes that there were over 60 mRNA-based cancer vaccines in development by 2024–2025, with first approvals anticipated by 2029.
Side Effects
Cancer vaccines generally have mild side effects. The most common are soreness, redness, or swelling at the injection site. Some patients develop a low-grade fever, chills, or fatigue for a short period. These reactions are signs of the immune system responding. Serious complications are rare, and doctors monitor patients closely to ensure the vaccine doesn’t trigger unexpected immune problems.
Overall, cancer vaccines are safer compared to chemotherapy or radiation.
4. Adoptive Cell Therapies (CAR T and TIL)
In adoptive cell therapy, doctors extract immune cells from a patient or donor, genetically modify them to be better at targeting and removing cancer cells, and then reintroduce them into the body to fight cancer.
Common Types of Adoptive Cell Therapies
There are two main treatments:
CAR T-Cell Therapy
In this approach, a specialist collects T cells from the patient’s blood and genetically engineers them to express a Chimeric Antigen Receptor (CAR) that targets a protein associated with cancer. After which, they expand and reinfuse these CAR T-cells into the body.
As of 2025, six CAR T-cell therapies have received FDA approval, all for the treatment of blood cancers. Examples include tisagenlecleucel (Kymriah) for acute lymphoblastic leukemia and axicabtagene ciloleucel (Yescarta) for large B-cell lymphoma.
CAR T-cell treatments have achieved high remission rates in refractory leukemia and lymphoma, with up to 50–80% of patients responding. However, due to its complexity, CAR T-cell treatments in the U.S. can cost between $500,000 and $1,000,000.
Side Effects
The most common side effect of CAR T-cell treatments is cytokine-release syndrome (CRS). Symptoms typically begin with high fever, chills, and fatigue. As it progresses, patients may develop low blood pressure, rapid heartbeat, difficulty breathing, or confusion. In the most severe cases, CRS can lead to organ failure if doctors fail to treat it quickly.
Another potential side effect is neurological toxicities. Patients may experience difficulty speaking, tremors, or trouble with memory and concentration. In more serious cases, seizures or loss of consciousness can occur.
Doctors can manage these reactions in the hospital, often using anti-IL-6 drugs.
Tumor-Infiltrating Lymphocyte (TIL)
TIL is a relatively new approach for treating solid tumors. Doctors extract T cells that have naturally penetrated a tumor biopsy, then expand those tumor-reactive T cells in the lab before infusing them back.
In February 2024, the FDA approved Lifileucel (Iovance’s AMTAGVI), the first TIL therapy, for melanoma that has progressed after checkpoint inhibitors. In the Lifileucel trial, 30% of heavily pre-treated patients had tumor shrinkage, and 40% of those responders were progression-free at one year.
As with any new medication, and with treatments in general, the trial’s participants encountered side effects, mostly due to the preparatory chemotherapy and high-dose interleukin-2 given with the treatment. Common toxicities included anemia, fevers, and drops in blood counts. Notably, Lifileucel did not cause the severe CRS or neurotoxicity observed with CAR T cells.
5. Cytokine Therapy
High-dose cytokines like interleukin-2 (IL-2) and interferon-alpha (IFN-α) were among the first immunotherapies.
- IL-2 induces complete remissions in some patients with advanced melanoma or kidney cancer. However, one of its severe side effects is capillary leak syndrome, wherein fluid leaks from blood vessels into tissues, causing very low blood pressure and swelling.
- IFN-α is a laboratory-made version of a natural protein that the immune system leverages to combat infections and cancer. In some patients, it helped slow cancer or reduce the chance of recurrence. However, since it has a tendency to cause flu-like symptoms, fatigue, and depression, doctors rarely use it as an immunotherapy for melanoma and some types of lymphoma today, especially since newer immunotherapies, like checkpoint inhibitors, are more effective and safer.
IL-2 and IFN-α are FDA-approved treatments for melanoma, hairy cell leukemia, follicular lymphoma, acquired immunodeficiency syndrome (AIDS)-associated Kaposi’s sarcoma, and renal cell carcinoma. However, as one review notes, they “have largely been superseded by alternative immunotherapies, particularly checkpoint blockade” due to better efficacy and tolerability. Newer versions of cytokine therapy, including engineered IL-2 that preferentially expands T cells without activating capillary-leak pathways, are under investigation and aim to preserve effectiveness while reducing side effects.
6. Oncolytic Viruses
These engineered viruses not only infect and kill tumor cells, but they also stimulate immunity. Talimogene laherparepvec (T-VEC) is an example of a modified herpes virus approved for advanced melanoma. Oncologists inject it straight into tumors, causing them to burst and release tumor antigens. Clinical researchers are working to expand this approach to other cancers in trials.
Side effects are mild to moderate. The most common include flu-like symptoms, along with redness or soreness at the injection site. Because the virus works inside the tumor, some patients notice swelling or irritation around the treated area.
More serious side effects are uncommon. In rare cases, the virus can cause infection in healthy tissues or spread in people with weakened immune systems. For this reason, doctors avoid using oncolytic virus therapy in patients with severe immune deficiency or active infections.
7. Intravesical BCG
For bladder cancer, doctors may order a treatment called Bacillus Calmette-Guérin (BCG) after surgery. BCG is a weakened form of the bacteria used in the tuberculosis vaccine. When doctors place it into the bladder through a catheter, it triggers a local immune reaction. The immune system becomes more active in the bladder lining and attacks any remaining cancer cells after surgery.
Physicians have used BCG for decades, and it’s still one of the most effective treatments for early-stage bladder cancer. Patients receive it once a week for several weeks, and sometimes as maintenance treatments over the course of many months.
Most side effects remain limited to the bladder and urinary tract. Common ones include burning during urination, frequent urination, or mild fever. In rare cases, the bacteria can spread beyond the bladder and cause infection.
Reassurance NOT to Fear the Side Effects of Immunotherapy
Although immunotherapy can cause side effects, ocologists have developed ways to manage them. Doctors recognize its risks and take preventive steps, including regular symptom checks and blood tests. If side effects occur, most improve once treated, and many patients can continue therapy safely.
Top Three Benefits of Immunotherapy
Immunotherapy has revolutionized the field of cancer treatment by improving prognoses and survival rates for millions of people worldwide. While side effects and limitations remain, clinical researchers are on a mission to overcome them, continuing to make progress in improving current breakthroughs while developing new immunotherapy approaches.
At present, immunotherapy prevails over conventional cancer with the following advantages:
1. More Targeted Action, Fewer Side Effects
Immunotherapy helps the immune system find proteins that exist mainly on cancer cells. When drugs or engineered immune cells attach to those proteins, they leave most normal cells unharmed. In contrast, chemotherapy damages rapidly dividing cells whether they’re cancerous or not. As a result, immunotherapy usually causes fewer common chemotherapy side effects such as hair loss, nausea, vomiting, and nerve damage.
2. Potential for Long-Lasting Protection
The immune system can remember threats through a process called immunological memory. If treatment successfully trains the immune system to recognize a cancer cell, the body may continue to fight those cells even after therapy ends. Some patients with melanoma, kidney cancer, or lymphoma stay cancer-free years after stopping immunotherapy. This advantage sets immunotherapy apart from other treatments that may only work while patients are actively receiving them.
3. New, Effective Options When Standard Treatments Fail
For patients whose cancers don’t respond to chemotherapy or radiation, immunotherapy is another path. For example, checkpoint inhibitors have worked in patients with advanced lung cancer who had already tried chemotherapy. CAR T-cell therapy has helped patients with lymphoma and leukemia whose cancers did not respond to other treatments. For these individuals, immunotherapy may prolong survival or even produce remission when few other options exist.
The New Hope Unlimited Approach
Few treatment centers understand that every cancer diagnosis is unique like we do. That’s why our team reviews each patient’s medical history, tumor characteristics, and immune profile to determine whether immunotherapy is appropriate. Then, we’ll use results from clinical trials and current medical guidelines to recommend the treatments most likely to work, whether it involves checkpoint inhibitors, monoclonal antibodies, or a completely different approach. Our goal is to maximize the benefits of immunotherapy while minimizing risks.
If you or a loved one is seeking safer, less-invasive treatment options, we’re here to answer your questions and create a plan for your specific diagnosis. Contact New Hope Unlimited to learn how immunotherapy and other personalized therapies can give your immune system the strength to fight back.
