Research
Immune Modulation (IM®) - Beyond Microwave Ablation
Either used alone or as an adjuvant with existing treatments, microwave immune-modulating (IM®) activation actions can be inducing, enhancing, or suppressing an immune response and the effects can be local to systemic from the point application. This offers innovation in many areas of intervention across the following fields of medicine:
- Gynaecology
- Dermatology
- Pre-cancer
- Oncology
- Cardiovascular
Displacement of existing destructive and surgical interventions is possible by harnessing the immune system of the patient to restore tissues to pre-disease state and treating the condition, not just the symptoms. In the case of viral infection by HPV, microwave IM® also disrupts the replication cycle[1]. IM® is achieved by raising the temperature of the target tissues in an accelerated manner into the fever range (also known as hyperthermia region) for a brief duration of between 2-60 seconds. Emblation has unique IP coverage for the treatment of the conditions listed and also for the design of microwave elements needed to achieve IM® in the diseased tissues.
By transforming the way microwave energy is being used in global healthcare and redefining the role medical devices play in the management of complex conditions, Emblation's product pipeline is truly unique – presenting opportunities for both commercialisation and strategic collaborations.
[1] "Growth potential and apoptosis is inhibited by localised topical microwave energy in HPV16-positive cervical tumour cells in 3D tissue culture models" M. Conley, A. Stevenson, S. Graham. EUROGIN 2018, Lisbon (2018).
Oropharyngeal squamous cell carcinoma (OPSCC) is a subset of squamous cell carcinoma (SCC) associated with human papillomavirus infection (HPV). These changes start after sexual transmission of HPV and develop over many years in a similar way to pre-cancer of the cervix.
The regions affected are: base of the tongue, lingual and palatine tonsils, hypopharynx, and soft palate.
While the rate of head and neck cancer has decreased in recent decades, the prevalence of OPSCC has risen dramatically. In the USA, 3 of 4 newly diagnosed oropharyngeal carcinomas are HPV-positive, and the prevalence has already overtaken that of HPV related cervical cancer. The American Cancer Society estimates that in 2018 there will be 51,500 patients diagnosed with oral cavity or oropharyngeal cancer, and an estimated 10,000 people will die of these cancers. Population-level incidence of HPV-positive oropharyngeal cancers increased by 225% from 1988 to 2004, and there continues to be around a 20% annual growth of incidence. A recent study found the prevalence of any oral HPV among male adults in the USA aged 18–69 was 11.5% (approximately 12 million male individuals). Before the cancer is detected, the dysplastic HPV region in the oral cavity can linger for many years, and there remains an estimated 500,000 males with pre-cancer in the oral cavity.
Treating tissues in-situ by microwave could stop the virus replication and simultaneously recruit the body's immune system to heal the infected cells, restoring the tissues without the need for disfiguring, invasive surgery.
DescriptionBarrett's oesophagus is the most common pre-cancerous condition of the oesophagus. It is a condition where the lining cells of the oesophagus become abnormal.
The areas of dysplasia in the oesophagus are similar to the infected transition regions in cervical pre-cancer and OPSCC. Chronic reflux over many years is the main cause of this pre-cancer.
Medicinal treatments can reduce the impact of further damage by reflux but most subsequent interventions are focussed on killing the abnormal cells. Traditional coagulation methods effectively ablate cells, but can lead to scar tissue and increase the risk of rupturing the tissue wall.
Microwave energy can deliver protective, anti-inflammatory and restorative effects when delivering hyperthermia range temperatures[2,3]. With local immune system recruitment initiated by microwave treatment, restoration of the tissue is possible without the traditional invasive side effects.
[2] "Fever-range hyperthermia improves the anti-apoptotic effect induced by low pH on human neutrophils promoting a proangiogenic profile", Díaz et al., Cell Death & Disease Volume 7, Page e2437 (2016) doi.org/10.1038/cddis.2016.337
[3] "Inducible protective processes in animal systems XV: Hyperthermia enhances the Ethyl methanesulfonate induced adaptive response in meiotic cells of grasshopper Poecilocerus pictus", Egyptian Journal of Medical Human Genetics, Volume 17, Issue 2, April 2016, Pages 173-184 doi.org/10.1016/j.ejmhg.2015.11.002
Inflammation and Thrombosis in Coronary arteries remain a risk despite stenting and drug interventions. There is still no known therapy to reverse Atherosclerosis.
Atherosclerosis is a syndrome primarily caused by the inflammatory response in blood vessels (in particular arteries) to the build-up of lipids, cholesterol crystals and calcified plaques. Without treatment, these vessels can become blocked either by the build-up of deposited lipids, cholesterol crystals and plaques or through the formation and subsequent rupture of a thrombus. Thrombus rupture can lead to a clot either at the site of an atherosclerotic plaque or further downstream, causing a cerebral infarction in the carotid artery (commonly known as a stroke), or acute myocardial infarction in the cardiac arteries (commonly known as a heart attack).
Bare metal stents used to treat this condition peaked in the USA in the early 2000s with more than 600,000 fitted annually. The switch to drug eluting stents peaked in 2006 with over 700,000 stents fitted.
Microwave energy can deliver protective, anti-inflammatory and restorative effects when delivering hyperthermia range temperatures. The treatment could promote endothelialisation and reduce late thrombosis risks.
Emblation is engaged with the University of Glasgow's Institute of Cardiovascular & Medical Sciences and Institute of Infection, Immunity & Inflammation.
The most common types of skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Non-melanoma skin cancers (NMSC) rarely spread to other parts of the body and SCC can form from Actinic keratosis (AK), a type of pre-cancerous skin lesion.
BCC
Basal cell carcinoma (BCC) is a cancer that begins in the lower part of the epidermis (the outer layer of the skin). Cumulative DNA damage from UV exposure leads to mutations and accounts for most BCC origins. Typically there is a 20 to 50 year latency between initial UV damage and any tumour onset. In the USA, 4.3 million cases of BCC are diagnosed each year.
AK
Actinic keratosis (AK) are also known as solar keratosis due to the origin of their formation being driven by over-exposure of skin to the sun. Abnormalities in DNA synthesis in keratinocytes in the skin around the lesion suggest that there is a gradual stepwise progression from sun-damaged epidermis, to squamous cell carcinoma. In total there are more than 5 million AK treatments carried out in the USA every year with an annual increase of 6%.
Traditional treatment options for BCC and AK are often invasive, involving excision, laser, cryotherapy, and photodynamic therapy, where scarring is common. Other treatments require strict adherence over many months and can be uncomfortable for patients.
Emblation is engaged in clinical research with Dermatologists at the University of Dundee's Division of Cancer Research and Ninewells Hospital, Dundee UK.
Cervical intra-epithelial neoplasia (CIN) is a pre-cancerous lesion that describes changes in the squamous epithelium cells of the cervix. These changes are caused by the HPV virus after sexual transmission and develop over many years.
Distinct types of the HPV family such as HPV-16 are among the strongest human carcinogens (World Health Organization class I carcinogen) and are responsible for all cervical cancers.
The American Cancer Society estimates 13,000 new cases of invasive cervical cancer in 2018, with a predicted 4,000 deaths. However, the volumes of cervical pre-cancers are considerably more common, with an excess of 1 million annual CIN treatments in the US alone.
Traditional treatment options are invasive, whereby cervical tissue is removed, leading to side effects such as post-procedural pain. Treating tissue in-situ using microwave IM® could remove the need for traditional invasive surgery.
Emblation is engaged with HPV experts at the University of Glasgow's MRC-Centre for Virus Research.
Anogenital intra-epithelial neoplasia (AIN) is a pre-cancerous lesion affecting the squamous epithelial cells of the anus. These changes are caused by the HPV virus after sexual transmission and develop over many years.
Much in the same way as the cervix is susceptible to the HPV virus, so is the anus. Left undiagnosed or untreated, anal cancer will develop.
Traditional treatment options are invasive whereby anal tissue is removed because the body has been unable to detect the infection and fight it with its immune system. Invasive interventions on the anus often lead to short term pain and side effects whilst adverse events or complications with the colon are also possible. Treating tissue in-situ using microwave IM® could remove the need for traditional invasive surgery.
Emblation is engaged with HPV experts at the University of Glasgow's MRC-Centre for Virus Research.
Infection with non-oncogenic, low-risk human types of HPV (mainly types 6 and 11) is associated with development of genital warts. The HPV infection occurs after sexual transmission and the warts may develop months after initial contact.
In men, genital warts can grow on the penis, near the anus, or between the penis and the scrotum. In women, genital warts may grow on the vulva and perineal area, in the vagina and on the cervix. Genital warts vary in size and may not even be visible to the naked eye.
During 2013–2014, the prevalence of any genital HPV for adults aged 18–59 was 45.2% in men and 39.9% in women – with 90 million cases in the USA alone.
Working with the University of Glasgow's MRC-Centre for Virus Research we are at the forefront of microwave-viral interactions, see our joint press release.
Melanoma is a disease where malignancy (cancer) forms in melanin cells found in the epidermis.
Cumulative damage from UV exposure and genetic disposition leads to mutations in a number of oncogenes in melanocytes (cells that colour the skin) found in the basal layer. What makes melanoma more dangerous than other skin cancers is its predisposition to invade nearby tissues and spread to other parts of the body (metastasise).
Melanoma is treated with a combination of surgery, traditional cytotoxic chemotherapy, targeted therapies, and immune-based therapies. Melanoma leads to substantial direct medical care costs with over 180,000 annual cases in the USA alone.
Emblation is engaged in clinical research with Dermatologists at the University of Southampton.
Atherosclerosis in other arteries of the body away from the heart can also follow the same aetiology. Areas treated with the same methodology of balloon and stent include carotid, aorta, iliac, femoral, popliteal and tibial arteries.
Atherosclerosis is a syndrome primarily caused by the inflammatory response in blood vessels to the build-up of lipids, cholesterol crystals and calcified plaques. Without treatment these vessels can become blocked, either by the build-up of deposited lipids, cholesterol crystals and plaques, or through the formation and subsequent rupture of a thrombus.
Annual treatments in the USA in the peripheral region using stents and balloons totals 1.4 million, with subsequent restenosis accounting for 15% of these interventions.
Microwave energy can deliver protective, anti-inflammatory and restorative effects when delivering hyperthermia range temperatures. The treatment could promote endothelialisation and reduce late thrombosis risks.
Emblation is engaged with the University of Glasgow's Institute of Cardiovascular & Medical Sciences and Institute of Infection, Immunity & Inflammation.
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