Immunotherapy for Head and Neck Cancer

Oral and oropharyngeal cancer (commonly referred to as head and neck cancer; HNSCC), grouped together, is the sixth most common cancer in the world, with more than 400,000 new cases each year. HNSCC is the second most common malignancy in Malaysia encompassing 13.2% of the total cancer incidence. In the UK, incidence of HNSCC has risen dramatically since the late 1970s (+92%) to over 7500 cases/year. Management of HNSCC patients is often by a costly multidisciplinary approach involving surgery and/or radiotherapy followed by reconstruction and rehabilitation. Treatment results in considerable physical and psychological morbidity and may not prolong life. The 5-year survival rates for HNSCC have been relatively static for decades at around 50-60%. It is clear than new treatments are required. Immunotherapy represents the most promising new cancer therapy for several decades. These treatments harness the power of the patient's immune system to fight the cancer, in the same way that the immune system might fight a virus. Cancers are recognised by the immune system as foreign' because they express proteins (antigens) not usually found in normal tissues. Some patients have a strong immune response against their cancer, causing immune cells (killer lymphocytes) to attack and destroy cancer cells. Immunotherapeutic drugs have been designed to boost this response, enhancing lymphocyte killing, and these have produced exciting clinical results in lots of cancer types. However, in most HNSCC patients, cancers do not provoke a strong immune response. By turning cancer antigens into powerful vaccines we can make the immune system recognise and react to the cancer; by combining the vaccines with other immunotherapeutic drugs, our hope is that we can generate an overwhelming immune attack against the cancer. The Cancer Research Malaysia (CRM) team have identified two novel cancer antigens (MAGED4B, FJX1) present in HNSCC in Malaysian patients. Notably, these cancer antigens are also expressed by UK HNSCC patients. The purpose of this study is to make vaccines against these antigens, using a novel vaccine design developed by the University of Southampton (UoS) that has previously been tested clinically. The new vaccines will be tested in a humanised mouse cancer model developed by the CRM team. The vaccines will be combined with several types of immunotherapeutic drugs designed to boost lymphocyte killing power, to identify the most effective combination. The UoS team has extensive experience in examining patients' immune responses to cancer, and will examine the visibility of MAGED4B/FJX1 antigens to the immune system of HNSCC patients. Finally, the UoS team will develop new mouse models of HNSCC which will form the basis for immunotherapy testing in future studies. If successful, the results from this pre-clinical study will be used to develop early phase clinical testing of vaccine combinations in both countries.