The immune system is the body’s natural defence system that helps protect from infections and diseases. When a foreign organism enters the body, the immune system recognises it and then attacks it, preventing it from causing harm. However, with cancer cells, the process is different.1 The immune system doesn’t always recognise cancer cells because they disguise themselves as normal cells. T-cells, white cells that are part of the immune system, have been a major focus in research due to their ability to therapeutically manipulate antitumour immunity.2 Innovative new therapies are now using this pathway in an attempt to slow the progression of certain tumours, including blood cancers.
T-cells have a protein on their surface called programmed death-1 (PD-1), which is known as a “checkpoint” to determine whether they should attack tumour cells, or shut themselves down. However, many cancers have found ways to manipulate this checkpoint. For example when PD-1 binds with a programmed death-ligand 1 (PD-L1) on another cell, the T-cell becomes inactivated, hence losing its ability to fight.2
New immunotherapy research is examining whether antibodies that block the PD-1/PD-L1 pathway can awaken and reactivate T-cells so they can once again kill tumour cells.3 There are existing therapies designed to work with the immune system to combat cancer, but PD-1 and PD-L1 inhibitors may hold a unique potential for some hard-to-treat cancers.3
“It’s really the first time the field is seeing very clear mechanistic single-agent activity, particularly in tumours that historically have not been very responsive to immunotherapy,” said Robert Hershberg, Senior Vice President, Immuno-Oncology at Celgene Corporation. “I think there’s very little doubt now that the future of oncology is inextricably linked to the immune system.”
While targeted therapies effectively shut down just one target within cancer cells, immunotherapy has more widespread effects, working with the body’s immune system as a whole to make it more difficult for the cancer to survive.1
Early clinical research suggests that at least some solid tumour cancers, including melanoma, respond to immunotherapy.3 A new collaboration between AstraZeneca and Celgene will now examine whether blood cancer patients, who are in need of new treatment options, might also benefit.4
The early findings in blood cancers have been promising.3 Blood cancers affect the blood, bone marrow and lymphatic system and tend to fall into three main groups: leukaemia, lymphoma and myeloma.5 Myeloma cells, for example, have been shown to have high levels of PD-L1.6 Also, high response rates to an investigational anti-PD-L1 antibody have been recently noted for patients with Hodgkin’s lymphoma.
In the future, combination therapy with PD-1 and PD-L1 antibodies could be even more advantageous.
2 Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews Cancer 12, 252-264 (April 2012)
3 McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Medicine 2013; 2(5): 662–673
4 Celgene corporation enters into strategic immune-oncology collaboration with AstraZeneca to develop PDL-1 inhibitor program for patients with serious blood cancers. Press release: 24 April 2015. Available from: http://files.shareholder.com/downloads/AMDA-262QUJ/182752263x0x823517/0791D850-A74F-4601-B936-0DD830FD826E/CELG_News_2015_4_24_General_Releases.pdf
5 Anthony Nolan. What is blood cancer. Available from: http://www.anthonynolan.org/patients-and-families/blood-cancers-and-blood-disorders/what-blood-cancer [Last accessed May 2015]
6 Atanackovic D, Luetkens T and Kroger N. Coinhibitory molecule PD-1 as a potential target for the immunotherapy of multiple myeloma. Leukemia (2014) 28, 993–1000
7 Shi L et al. The role of PD-1 and PD-L1 in T-cell immune suppression in patients with haematological malignancies. Journal of Hematology & Oncology 2013, 6:74
Date of Preparation: June 2015