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.

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Immunotherapy in a nutshell

Immuno-oncology

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.