What is IO?
Immunotherapy is a fundamentally different approach to cancer treatment.
While traditional chemotherapy drugs display more general toxicity acting not only on cancer cells, but also normal cells, IO treatments unlock the body’s own immune system to fight cancer. In essence, IO is a broad therapeutic master plan to outsmart cancer, now becoming available in the clinic with an unprecedented number of new investigational drugs currently developed by established and emerging pharma companies in the world.
Immunotherapy in a nutshell
Immuno-oncology (IO) offers new promising treatment options for late stage cancer. Until recently, cancer treatments consisted of surgery, radiation therapy, chemotherapy and targeted therapy. While often effective in patients with early, non-metastatic cancers, these modalities generally fail to produce lasting benefits in patients with late-stage cancer.
Immunotherapy drugs have been approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for many cancer types. In most developed countries IO treatment has become standard of care for the treatment of several cancers, including metastatic melanoma, advanced non-small cell lung cancer, squamous cell carcinoma of the head and neck and renal cell carcinoma. IO therapies have been studied and approved inreasingly also as adjuvant therapy after surgery.
Traditional treatments, in particular chemotherapy, often have serious side effects due to non-tumor specific toxicity and these adverse effects can have tremendous negative impact on the patients’ quality of life. Cancer immunotherapy has revolutionized cancer treatment by offering treatment options for previously untreatable forms of cancer such as advanced lung cancer or metastatic melanoma. However, also immunotherapies can have serious adverse effects, which can affect skin, colon, endocrine organs, liver and lungs.
Types of immunotherapy
Rather than aiming treatments directly at the tumor, immunotherapies engage the immune system to recognize and eradicate tumor cells. Currently, the most commonly used immunotherapies in the clinic are immune checkpoint inhibitors (ICIs). Interaction of checkpoint receptor/ligand pairs on the surface of immune cells and/or target cells, for example PD1/PD-L1 and CTLA-4/B7-1/B7-2, causes inactivation of the immune cell. Immune checkpoint proteins thus function as fail-safe mechanisms that in normal physiology modulate the duration and amplitude of a physiological immune response by regulating the balance between co-stimulatory and inhibitory signals.
Cancer cells hijack immune checkpoints to avoid detection by the patient’s immune system. ICIs block the immune checkpoint proteins, thus releasing the brakes on the immune system and reinvigorating the anti-cancer immune response, which can lead to durable remission. Most ICIs used in the clinic are anti-CTLA-4 and anti-PD-1/PD-L1 antibodies.