Immuno-Oncology (Immunotherapy for Cancer)

What Is Immunotherapy?

Immunotherapy refers to treatments that influence the human immune system. A distinction is made between four different methods:

• Stimulating
• Suppressing
• Substituting
• Modulating

Stimulatory therapies include vaccinations and the administration of general immune stimulants. The immune system is stimulated to provide more defense mechanisms in more white blood cells and specific antibodies. White blood cells are part of the congenital immune system and generally fight anything foreign in the body, such as pathogenic bacteria. Antibodies are produced by a subspecies of white blood cells called B-cells and bind specifically to a type of cell or virus. This binding immobilizes the invaders and renders their toxins harmless. In addition, this binding helps other immune cells to detect and eliminate foreign substances. Vaccinations bring dead or weakened pathogens into the organism so that the body is stimulated to synthesize defense cells and antibodies against specifically this type of pathogen. Immunostimulants can be the body's substances, such as interleukins or interferons, secreted by the body after an infectious illness such as a cold. But certain bacteria and plants also produce such immunostimulants, strengthening the body's defenses after extraction and preparation.

Suppressive treatments are commonly used for autoimmune diseases, allergies, and after organ transplants. In autoimmune diseases and allergies, a misdirected and exaggerated immune response to harmless and endogenous substances occurs. The goal in treating these diseases is to shut down the immune system so that it does not cause damage to the patient's organism. After organ transplantation, the transplant is rejected because it is recognized as foreign by the body's immune cells. To prevent this reaction, the immune system must also be suppressed.

In the substitutive procedure, missing and deficient antibodies are supplied to the body. This occurs with passive vaccination or with the administration of monoclonal antibodies that specifically bind to the desired structures and destroy or render them harmless. An example of this is the drug Abciximab, which binds to the surface of platelets, preventing their aggregation. Abciximab is used successfully in specific patient groups to avoid heart attacks.

Modulating procedures include desensitization and immunoadsorption. However, desensitization is still the only causal therapy for allergies. For this purpose, small amounts of the allergy-causing substance, the so-called allergen, are administered to the body, and the dose is increased at each session so that the immune system can get used to the harmless substance and the immune response becomes increasingly weaker. Immunoadsorption is mainly used in the treatment of autoimmune diseases. Blood is taken from the patient in this process, and antibodies against the body's structures are filtered out in adsorbers machines.

Which Procedures Are Used in Cancer Therapy?

Three classic forms of treatment and their combinations are used to treat oncological diseases:

• Chemotherapy
• Surgical resection
• Radiotherapy

In chemotherapy, drugs are usually applied into the bloodstream to multiply cells throughout the body rapidly. However, by adding various DNA errors, these cells are damaged. In addition, since tumor cells divide quickly in the body and cells of the mucous membranes and hair follicles, these tissues are also attacked by chemotherapy.

A solid tumor can be removed in surgical resection. In this process, diseased tissue is removed with a safety margin of healthy tissue. The removed tissue is always examined pathologically for further histological clarification of the tumor. Subsequently, further therapeutic measures can be determined.

In radiation therapy, photon or proton beams are explicitly directed at the tumor to be treated, which damages the DNA of the tumor cells to varying degrees, depending on the cell's cycle phase during irradiation. In addition, since the radiation passes through other tissues before reaching the tumor, it can cause side effects such as radiodermatitis after breast irradiation or continence disorders after prostate irradiation.

In addition to the three classic treatment methods, newer procedures have also become established in the daily routine in clinical practice when treating cancer. These include:

• Immunotherapy
• A therapy with radiopharmaceuticals

How Does Immunotherapy Work for Cancer?

The immune system significantly impacts cancer, but unfortunately, most cancers can evade the immune system. Oncologic immunotherapy addresses this issue by applying stimulatory and substitutive therapies.

Stimulating Immunotherapy

The stimulating procedure can be divided into specific and non-specific therapy. The former stimulates only certain cells in the body or activates the immune system only against particular target structures. In contrast, the non-specific treatment stimulates the immune system as a whole. Promising in this approach is the administration of so-called immune checkpoint inhibitors. Tumor cells can alter these checkpoints of the immune system so that immune response does not appear. By administering the checkpoint inhibitors, this effect of the tumor cells can be prevented.

Passive Cancer Immunotherapy

Passive cancer immunotherapy involves treatment with monoclonal antibodies. This refers to antibodies directed against a single surface structure (epitope). The body's antibodies play only a minor role in the defense against cancer cells since the organism does not recognize them as foreign or dangerous. However, monoclonal antibodies play a role in both the diagnosis and therapy of cancer. Marked antibodies can be used to detect specific epitopes and associated particular cells. This diagnostic step provides information about the size, distribution, and localization of the tumor disease. In 1997, the first monoclonal antibody for therapeutic purposes, Rituximab, was approved in the United States. Therapeutic antibodies bind to surface structures specific to the tumor cell or messenger substances responsible for tumor growth. One effect of antibodies is the cross-linking of tumor cells into complexes, which triggers growth-inhibiting or degrading signals in the tumor cells. Another effect is the binding of the antibodies against growth signals so that growth is inhibited or stopped.

What Cancers Can Be Treated with Immunotherapy?

Immune checkpoint inhibitors are currently used to treat the following diseases, among others:

• Melanoma
• Non-small cell lung cancer (NSCLC)
• Clear cell renal cancer
• Squamous cell carcinoma

The following monoclonal antibodies are currently used to treat diseases (the list is not complete). The suffix -mab stands for three letters of the words monoclonal antibody.

• Alemtuzumab: acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL)
• Bevacizumab: colorectal cancer, breast cancer, NSCLC
• Cetuximab: colorectal cancer, head, and neck tumors
• Dinutuximab: neuroblastoma
• Ipilimumab: malignant melanoma
• Nivolumab: malignant melanoma and NSCLC
• Ofatumumab: CLL
• Olaratumab: sarcoma
• Panitumumab: epithelial growth factor (EGF)-receptor-expressing tumors
• Pembrolizumab: mesothelioma, malignant melanoma, NSCLC
• Rituximab: non-Hodgkin's lymphoma
• Ramucirumab: advanced gastric and colon cancer
• Trastuzumab: breast cancer, gastric cancer

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