Immunotherapy In-Depth

Immunotherapy has the potential to treat all cancers.

Immunotherapy enhances the immune system’s ability to recognize, target, and eliminate cancer cells, wherever they are in the body, making it a potential universal answer to cancer.

Immunotherapy has been approved in the U.S. and elsewhere as a first-line of treatment for several cancers, and may also be an effective treatment for patients with certain cancers that are resistant to prior treatment. Immunotherapy may be given alone or in combination with other cancer treatments. As of December 2019, the FDA has approved immunotherapies as treatments for nearly 20 cancers as well as cancers with a specific genetic mutation

Immunotherapy may be accompanied by side effects that differ from those associated with conventional cancer treatments, and side effects may vary depending on the specific immunotherapy used. In most cases, potential immunotherapy-related side effects can be managed safely as long as the potential side effects are recognized and addressed early.

• Cancer immunotherapy treats the patient—by empowering their immune system—rather than the disease itself like chemotherapy and radiation. Patients may be tested for biomarkers that may indicate whether cancer immunotherapy would be an effective treatment.
• Side effects of immunotherapy may results from stimulation of the immune system and may range from minor inflammation and flu-like symptoms, to major, potentially life-threatening conditions similar to autoimmune disorders.
• Common side effects may include but are not limited to skin reactions, mouth sores, fatigue, nausea, body aches, headaches, and changes in blood pressure.

Conventional cancer treatments also have a range of side effects with a wide range of severity.

• Chemotherapy is intended to target fast-growing cancer cells, so it may damage other fast-growing normal cells in your body. Common side effects may include but are not limited to hair loss, nausea, diarrhea, skin rash, and fatigue.
• Radiation uses radioactive particles to destroy cancer cells in a localized area, so it may damage other healthy cells in that area. Side effects may be associated with the area of treatment, such as difficulty breathing when aimed at the chest, or nausea when aimed at the stomach. Skin problems and fatigue are common.
• The goal of surgery is to remove the cancerous tumor or tissue and varies according to the type of surgery performed. Common side effects may include but are not limited to pain, fatigue, swelling, numbness, and risk of infection.

Cancer immunotherapy offers the possibility for long-term control of cancer.

Immunotherapy can “train” the immune system to remember cancer cells. This “immunomemory” may result in longer-lasting and potentially permanent protection against cancer recurrence.

Clinical studies on long-term overall survival have shown that the beneficial responses to cancer immunotherapy treatment can be durable—that is, they continue even after treatment is completed.

Cancer immunotherapy originated in the late 1890s with a cancer surgeon named Dr. William B. Coley (1862–1936). He discovered that infecting cancer patients with certain bacteria sometimes resulted in tumor regression and even some complete remissions. Advances in cancer immunology since Coley’s time have revealed that, in patients that responded to his treatment, his bacterial toxin therapy stimulated their immune systems to attack the tumors.

While Coley’s approach was largely dismissed during his lifetime, his daughter, Helen Coley Nauts, discovered his old notebooks and founded the Cancer Research Institute in 1953 to support research into his theory. In 1990, the FDA approved the first cancer immunotherapy, a bacteria-based tuberculosis vaccine called Bacillus Calmette-Guérin (BCG), which was shown to be effective for patients with bladder cancer.

While many of our cells grow and divide naturally, this behavior is tightly controlled by a variety of factors, including the genes within cells. When no more growth is needed, cells are told to stop growing.

Unfortunately, cancer cells acquire defects that cause them to ignore these stop signals, and they grow out of control. Because cancer cells grow and behave in abnormal ways, this can make them stand out to the immune system, which can recognize and eliminate cancer cells through a process called immunosurveillance.

However, this process isn’t always successful. Sometimes cancer cells develop ways to evade and escape the immune system, which allows them to continue to grow and metastasize, or spread to other organs. Therefore, immunotherapies are designed to boost or enhance the cancer-fighting capabilities of immune cells and tip the scales in the immune system’s favor.

Immunotherapy treatments can be broken down into five types:

1. Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers (known as antigens) on cancer cells, in order to disrupt cancerous activity, especially unrestrained growth. Some targeted antibody-based immunotherapies, known as antibody-drug conjugates (ADCs), are equipped with anti-cancer drugs that they can deliver to tumors. Others, called bi-specific T cell-engaging antibodies (BiTEs), bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. All targeted antibody therapies are currently based on monoclonal antibodies (clones of a parent bonding to the same marker(s)).
2. Adoptive cell therapy takes a patient’s own immune cells, expands or otherwise modifies them, and then reintroduces them to the patient, where they can seek out and eliminate cancer cells. In CAR T cell therapy, cancer-fighting T cells are modified and equipped with specialized cancer-targeting receptors known as CARs (chimeric antigen receptors) that enable superior anti-cancer activity. Natural killer cells (NKs) and tumor-infiltrating lymphocytes (TILs) can also be enhanced and reinfused in patients.
3. Oncolytic virus therapy uses viruses that are often, but not always, modified in order to infect tumor cells and cause them to self-destruct. This can attract the attention of immune cells to eliminate the main tumor and potentially other tumors throughout the body.
4. Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Cancer vaccines can be made from a variety of components, including cells, proteins, DNA, viruses, bacteria, and small molecules. Some versions are engineered to produce immune-stimulating molecules. Preventive cancer vaccines inoculate individuals against cancer-causing viruses and bacteria, such as HPV or hepatitis B.
5. Immunomodulators govern the activity of other elements of the immune system to unleash new or enhance existing immune responses against cancer. Some, known as antagonists, work by blocking pathways that suppress immune cells. Others, known as agonists, work by stimulating pathways that activate immune cells. Checkpoint inhibitors target the molecules on either immune or cancer cells, telling them when to start or stop attacking a cancer cell. Cytokines are messenger molecules that regulate maturation, growth, and responsiveness. Interferons (IFN) are a type of cytokine that disrupts the division of cancer cells and slows tumor growth. Interleukins (IL) are cytokines that help immune cells grow and divide more quickly. Adjuvants are immune system agents that can stimulate pathways to provide longer protection or produce more antibodies (they are often used in vaccines, but may also be used alone).

Chemotherapy is a direct form of attack on rapidly-dividing cancer cells, but this can affect other rapidly dividing cells including normal cells. When patients respond, the treatment’s effects happen immediately. These direct effects of chemotherapy, however, last only as long as treatment continues.

Immunotherapy treats the patient’s immune system, activating a stronger immune response or teaching the immune system how to recognize and destroy cancer cells. Immunotherapy may take more time to have an effect, but those effects can persist long after treatment ceases.

As of March 2022, the U.S. Food and Drug Administration had approved over 60 immunotherapies that together cover almost every major cancer type:

1. Aldesleukin (immunomodulator) for kidney cancer and melanoma
2. Alemtuzumab (targeted antibody) for leukemia
3. Amivantamab (bispecific antibody) for lung cancer
4. Atezolizumab (checkpoint inhibitor) for bladder, liver, and lung cancer, and melanoma
5. Avelumab (checkpoint inhibitor) for bladder, kidney, and skin cancer (Merkel cell carcinoma)
6. Axicabtagene ciloleucel (CAR T cell therapy) for lymphoma
7. Bacillus Calmette-Guérin [BCG] (vaccine) for bladder cancer
8. Belantamab mafodotin-blmf (antibody-drug conjugate) for multiple myeloma
9. Bevacizumab (targeted antibody) for brain, cervical, colorectal, kidney, liver, lung, and ovarian cancer
10. Blinatumomab (bi-specific T cell-engaging antibody) for leukemia
11. Brentuximab vedotin (antibody-drug conjugate) for lymphoma
12. Brexucabtagene autoleucel (CAR T cell therapy) for leukemia and lymphoma
13. Cemiplimab (checkpoint inhibitor) for lung cancer and skin cancer (basal cell carcinoma and cutaneous squamous cell carcinoma)
14. Cetuximab (targeted antibody) for colorectal and head and neck cancer
15. Ciltacabtagene autoleucel (CAR T cell therapy) for multiple myeloma
16. Daratumumab (targeted antibody) for multiple myeloma
17. Denosumab (targeted antibody) for sarcoma
18. Dinutuximab (targeted antibody) for pediatric neuroblastoma
19. Dostarlimab (checkpoint inhibitor) for uterine (endometrial) cancer
20. Durvalumab (checkpoint inhibitor) for lung cancer
21. Elotuzumab (targeted antibody) for multiple myeloma
22. Enfortumab vedotin-ejfv (antibody-drug conjugate) for bladder cancer
23. Gemtuzumab ozogamicin (antibody-drug conjugate) for leukemia
24. Granulocyte-macrophage colony-stimulating factor, or GM-CSF (immunomodulator) for neuroblastoma
25. Hepatitis B Vaccine (Recombinant) (preventive vaccine) for liver cancer
26. Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine, Recombinant (preventive vaccine) for cervical, vulvar, vaginal, and anal cancer
27. Human Papillomavirus 9-valent Vaccine, Recombinant (preventive vaccine) for cervical, vulvar, vaginal, anal, and throat cancer
28. Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant (preventive vaccine) for cervical cancer
29. Ibritumomab tiuxetan (antibody-drug conjugate) for lymphoma
30. Idecabtagene vicleucel (CAR T cell therapy) for multiple myeloma
31. Imiquimod (immunomodulator) for skin cancer (basal cell carcinoma)
32. Inotuzumab ozogamicin (antibody-drug conjugate) for leukemia
33. Interferon alfa-2a (immunomodulator) for leukemia and sarcoma
34. Interferon alfa-2b (immunomodulator) for leukemia, lymphoma, and melanoma
35. Ipilimumab (checkpoint inhibitor) for colorectal, liver, and lung cancer, and melanoma and mesothelioma
36. Isatuximab (targeted antibody) for multiple myeloma
37. Lisocabtagene maraleucel (CAR T cell therapy) for lymphoma
38. Loncastuximab tesirine​ (antibody-drug conjugate) for lymphoma
39. Margetuximab (targeted antibody) for breast cancer
40. Mogamulizumab (targeted antibody) for lymphoma
41. Naxitamab-gqgk (targeted antibody) for neuroblastoma
42. Necitumumab (targeted antibody) for lung cancer
43. Nivolumab (checkpoint inhibitor) for bladder, colorectal, esophageal, GEJ, head and neck, kidney, liver, lung, and stomach cancer, lymphoma, melanoma, and mesothelioma
44. Obinutuzumab (targeted antibody) for leukemia and lymphoma
45. Ofatumumab (targeted antibody) for leukemia
46. Panitumumab (targeted antibody) for colorectal cancer
47. Peginterferon alfa-2b (immunomodulator) for melanoma
48. Pembrolizumab (checkpoint inhibitor) for bladder, breast, cervical, colorectal, esophageal, head and neck, kidney, liver, stomach, lung, and uterine cancer as well as lymphoma, melanoma, and any MSI-H or TMB-H solid cancer regardless of origin
49. Pertuzumab (targeted antibody) for breast cancer
50. Pexidartinib (immunomodulator) for tenosynovial giant cell tumor
51. Polatuzumab vedotin (antibody-drug conjugate) for lymphoma
52. Poly ICLC (immunomodulator) for skin cancer (squamous cell carcinoma)
53. Ramucirumab (targeted antibody) for colorectal, esophageal, liver, lung, and stomach cancer
54. Relatlimab (checkpoint inhibitor) for melanoma
55. Rituximab (targeted antibody) for leukemia and lymphoma
56. Sacituzumab govitecan-hziy (antibody-drug conjugate) for bladder and breast cancer
57. Sipuleucel-T (vaccine) for prostate cancer
58. Tafasitamab (targeted antibody) for lymphoma
59. Tebentafusp-tebn (bispecific antibody) for melanoma
60. Tisagenlecleucel (CAR T cell therapy) for leukemia (including pediatric) and lymphoma
61. Tisotumab vedotin (antibody-drug conjugate) for cervical cancer
62. Trastuzumab (targeted antibody) for breast, esophageal, and stomach cancer
63. Trastuzumab deruxtecan (antibody-drug conjugate) for breast, esophageal, and stomach cancer
64. Trastuzumab emtansine (antibody-drug conjugate) for breast cancer
65. T-VEC (oncolytic virus) for melanoma

New immunotherapies are being developed and immunotherapy clinical trials are under way in nearly all forms of cancer.

People with mild autoimmune diseases are able to receive most immunotherapies. Typically, autoimmune treatment is adjusted and a checkpoint immunotherapy, such as those targeting the PD-1/PD-L1 pathway, is used. However, each patient should speak with his or her doctor regarding the options that are most appropriate.

People with HIV who are receiving effective anti-viral treatment and whose immune systems are functioning normally may respond to cancer immunotherapy and are therefore eligible to receive immunotherapy, both as a standard of care and as part of a clinical trial.

The administration and frequency of immunotherapy regimens vary according to the cancer, drug, and treatment plan. Clinical trials can offer many valuable treatment opportunities for patients. Discuss your clinical trial options with your doctor.

Immunotherapy treatments may take longer to produce detectable signs of tumor shrinkage compared to traditional therapies. Sometimes tumors may appear to grow on scans before getting smaller, but this apparent swelling may be caused by immune cells infiltrating and attacking the cancer. Many patients who experience this phenomenon, known as pseudoprogression, often report feeling better overall.

In certain cancer types, immune-related side effects may be linked with treatment success—specifically, melanoma patients who develop vitiligo (blotched loss of skin color)—but for the vast majority of patients, no definitive link has been established between side effects and immunotherapy’s effectiveness.

For more than 65 years, the Cancer Research Institute (CRI) has been the pioneer in advancing immune-based treatment strategies against cancer. It is the world’s leading nonprofit organization dedicated exclusively to saving more lives by fueling the discovery and development of powerful immunotherapies for all types of cancer.

CRI provides financial support to scientists at all stages of their careers along the entire spectrum of immunotherapy research and development: from basic discoveries in the lab that shed light on the fundamental components and mechanisms of the immune system and its relationship to cancer, to efforts focused on translating those discoveries into lifesaving treatments that are then tested in clinical trials for cancer patients.

Cancer immunology studies the relationship between cancer and the body’s immune system, including its innate ability to prevent or eliminate cancer cells, called immunosurveillance. Research shows that the body’s natural defense mechanisms can recognize and target cancer cells. Cancer immunologists focus on developing immunotherapies to boost those natural defenses.

Cancer immunotherapies also are known as biologic therapy, biotherapy, or biological response modifier therapy, and include checkpoint blockade, cancer vaccines, monoclonal antibodies, oncolytic virus therapy, T cell transfer, and other immune-modulating drugs such as cytokines and other adjuvant therapies. These effective ways for preventing, managing, or treating different cancers can be used in conjunction with surgery, chemotherapy, or radiation.

The earliest forms of what would later be considered the start of cancer immunotherapy originated with research done by Dr. William B. Coley (1862-1936), a cancer surgeon and father of CRI founder Helen Coley Nauts. He discovered that “killed” bacteria stimulated the immune system to attack cancer cells. Modern cancer immunology is based on more recent advances in scientific understanding of the immune system’s various components, their function, and their role in cancer control. Cancer immunology is a relatively young field, but advances in treatment are aided by donor support.

• Read our timeline of milestones in the field.
• Learn what immunotherapy is.
• Discover which immunotherapies are available for different cancers.
• Find out how different types of immunotherapy work.
• Get to know the scientists and patients behind the progress.
• Search for patient-specific resources.