New targeted approach to light-activated cancer drugs

Combination approach yields positive results<em> - News Release</em>

Imperial College London News Release

For immediate release
Thursday 8 November 2007

Combining light-activated cancer drugs with tumour-seeking antibodies could provide a more effective way of treating many cancers, according to new research published in advance online in the International Journal of Cancer. 

The study, which is due to appear in the December issue of the journal, describes how scientists have successfully attached 10 light-activated drug molecules to an antibody which recognises and homes in on the cancerous cells. The researchers have shown that using this method means highly potent drug molecules are delivered to precise cancer targets much more effectively than if they are not attached to the antibody.

Using light-activated drugs to treat cancer is known as photodynamic therapy (PDT). This treatment involves focusing drugs on diseased tissues, and then illuminating the area with a cold laser which sets off a chain reaction in the cancerous tissue, converting oxygen to a highly toxic type of oxygen-like bleach, which destroys cells in the vicinity. PDT has been shown to be successful in treating head and neck, prostate and skin cancers.

However, current PDT is limited by the inefficiency with which the light-activated drugs are able to specifically target tumours. This can mean that the light-activated drugs can circulate in the patient's body for some time after the treatment, leaving patients light-sensitive and prone to skin damage. The research team behind the new study think their results show they can solve this problem by ensuring the drugs get straight to the cancerous cells, and do not affect the rest of the body.

Dr Mahendra Deonarain from Imperial College London's Department of Life Sciences, lead author on the paper, explains: "PDT is a very promising way to treat cancer because it leaves patients with very little cosmetic scarring and there are low chances of drug resistance. We have shown that it’s possible to use tumour-seeking antibodies, like the ones used in drugs like Herceptin and Rituxan, to deliver these potent drugs accurately to the site of the cancer, minimising the risk of healthy tissue getting accidentally damaged in the treatment process, and maximising the number of cancer cells that are destroyed."

The research team, led by scientists from Imperial and the Imperial spin-out company PhotoBiotics, has shown that their antibody-carrying light-sensitive drugs have effected complete tumour regression in an animal model. Dr Deonarain explains that the next step is to take the study forward into clinical trials:

"We have shown that it’s possible to attach these drug molecules to these targeting antibodies without destroying the useful properties of the antibody itself. Our initial results are extremely promising and we're hoping to take this forward into clinical trials in the near future. Our work is expanding the applications of PDT for many cancers and we're excited about moving towards making targeted PDT a clinical reality."

PhotoBiotics has 4 filed patents protecting this new technology and is currently completing further pre- clinical studies with a view to moving into clinical trials within the next three years.

For more information please contact:
Danielle Reeves, Imperial College London Press Office,
Tel: +44 (0)20 7594 2198
Mob: +44 (0)7803 886248
Email: Danielle.reeves@imperial.ac.uk

Notes to Editors:

1. The research paper is available here: http://www3.interscience.wiley.com/cgi- bin/fulltext/116837461/HTMLSTART

2. 'Targeted photodynamic therapy with multiply-loaded recombinant antibody fragments', The International Journal of Cancer, published online 31 October 2007.

Manpreet Bhatti (1), Gokhan Yahioglu (2, 3), Lionel R. Milgrom (2, 3), Mitla Garcia-Maya (1), Kerry A. Chester (4), Mahendra P. Deonarain (1).

1. Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, Exhibition Road, London, United Kingdom
2. PhotoBiotics, 21 Wilson Street, London EC2M 2TD, United Kingdom
3. Department of Chemistry, Faculty of Natural Sciences, Imperial College London, Exhibition Road, London, United Kingdom
4. Department of Oncology, Royal Free and University College Medical School, University College London, London, United Kingdom.

3. About Imperial College London

Rated as the world's fifth best university in the 2007 Times Higher Education Supplement University Rankings, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts over 12,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and management and delivers practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

With 66 Fellows of the Royal Society among our current academic staff and distinguished past members of the College including 14 Nobel Laureates and two Fields Medallists, Imperial's contribution to society has been immense. Inventions and innovations include the discovery of penicillin, the development of holography and the foundations of fibre optics.

This commitment to the application of our research for the benefit of all continues today with current focuses including interdisciplinary collaborations to tackle climate change and mathematical modelling to predict and control the spread of infectious diseases.

The College's 100 years of living science will be celebrated throughout 2007 with a range of events to mark the Centenary of the signing of Imperial's founding charter on 8 July 1907.

Website: www.imperial.ac.uk

4. About PhotoBiotics

Photobiotics is a spin-out company from Imperial College London set up in 2001 to develop novel biologically- targeted photodynamic therapeutic (PDT) agents. Created out of a unique, in-house and world-class expertise in chemistry, physics, and biotechnology, these new PDT agents will be able to specifically target and destroy tumours, a range of other proliferating tissues, and pathogenic organisms. Potential applications of this new technology include cancer, age-related macular degeneration (AMD), 'irresistible antibiotics' and many more.

PhotoBiotics' uniquely targeted approach to PDT will ensure the photosensitising agent specifically localises only in pathological tissues. This will greatly improve PDT's therapeutic margin, drastically reducing photosensitivity and therefore allow for its more effective use in a wide range of cancers and AMD. It will also enable PDT’s wider application in indications such as microbial infections, restenosis following angioplasty, and various proliferative skin conditions.

PhotoBiotics believes its unusually distinctive and multidisciplinary approach to PDT has the potential to offer strikingly improved treatment regimes that could replace conventional PDT and significantly extend its market penetration. Relatively few organisations worldwide have the skills to develop PDT technology, and PhotoBiotics is highly distinctive in possessing an integrated capability involving chemistry, laser physics and biology. The science is challenging and is delivering on its promise in a series of successful in vitro and in vivo trials. The founde rs have already established successful research collaborations. Accordingly PhotoBiotics will seek to align itself with other PDT and market focussed companies in cancer, ophthalmics and other markets researching, discovering and developing improved therapeutic modalities.

5. About PDT

PDT has an established niche in the treatment of certain cancers and in age related macular degeneration (AMD), which is a common cause of visual impairment in the over-50’s. However, PDT’s clinical development and use have been slow to evolve owing mainly to the novelty of the treatment regimen. Its growth has been further restricted by the technical limitations of existing approaches; specifically the therapeutic margin, which is the ratio of effective dose to toxic dose.

The main toxicity arising from current PDT is post-treatment systemic photosensitivity. The photosensitising agent remains in the system for up to six weeks post treatment in some cases, and when it reaches the skin, patients can become exquisitely photosensitive sensitive to ambient light even on cloudy days, leading to symptoms akin to acute sunburn in uncovered parts of the body.

Website: www.photobiotics.com