Over the last few years, new breakthroughs in lung cancer treatment have occurred through the results from clinical trials with immunotherapy. Several “new” agents are developed specifically targeting the immune mechanisms involved when the cancer is trying to avoid the patients’ immune system.

However, antibodies are developed to block specific “escape mechanisms,” so the immune system can be activated and fight the malignant process.

No small battle

Most advanced in clinical studies and, which have resulted in very encouraging results, in lung cancer and other cancers’ treatment are antibodies, which block the reaction between the cancer cells and specific lymphocytes (T-cells).

When cancer cells are recognized by T-lymphocytes—an important component in the normal immune system—specific receptor proteins are activated both on cancer cells and T-lymphocytes, among them the Programmed Death 1 (PD-1) Protein on T-lymphocytes and its counterpart on cancer cells, the Programmed Death Ligand 1 (PD-L1). The connection between those proteins will lead to suppression of the T-lymphocyte function, which is the opposite of what you want in order to fight the cancer process.

The antibodies developed by several pharmaceutical companies, which block the connection of PD-1 and PD-L1, result not in suppression of the T-lymphocytes but activation of the T-lymphocytes and the immune system. This, in turn, leads to blocking the progression of cancer cells and eventually kills the cancer cells.

"Antibodies are developed to block specific 'escape mechanisms,' so the immune system can be activated and fight the malignant process."

Agents of good

Several anti-PD-L1/PD-1 antibodies are developed and several have already demonstrated very encouraging effects both in lung cancer and other cancers, such as melanoma and renal cell carcinoma. In lung cancer, the results from clinical studies are from patients who previously failed previous treatments like chemotherapy. However, with immunotherapies the prognosis for many lung cancer patients in this situation has been changed significantly, particularly patients with advanced Non-Small Cell Lung Cancer (NSCLC), whose tumors express the special protein (PD-L1) on the tumor cells.

Two agents in this family have already been approved by the FDA, namely pembrolizumab (Keytruda, Merck) and nivolumab (Opvidio, BMS). Yet several other similar agents are under clinical development and expected to get approval within the next 2 years. While the clinical results so far, which have led to FDA approvals, are for patients who have failed previous treatment such as chemotherapy, clinical studies for first-line therapy are ongoing and preliminary data is very encouraging. It could well be expected that when results are ready these agents will also demonstrate with great effect, as first-line therapy available for use in patients with advanced NSCLC.

The side effects from the immune therapy agents are modest compared to conventional chemotherapy. Few patients (less than 5 percent) will eventually develop more serious side effects from the immune therapy. Meanwhile, clinical studies that combine immune therapy with other agents continue to take place and offer wider realms of comfort for the future of this harrowing diagnosis.