Médicaments photodynamiques.

(Dec. 21, 2007) — Researchers from the Universities of Warwick, Edinburgh, Dundee and the Czech Republic’s Institute of Biophysics have discovered a new light-activated platinum-based compound that is up to 80 times more powerful than other platinum-based anti-cancer drugs and which can use "light activation" to kill cancer cells in much more targeted way than similar treatments.


Les chercheurs ont découvert un médicament à base de platinium activé par la lumière qui est jusqu'à 80 fois plus puissant que les autres médicaments à base de platinium et qui est plus ciblé que les autres à cause de son activation par la lumière.

The platinum-based compound known as "trans, trans, trans- [Pt(N3)2(OH)2(NH3)(py)]", or a light activated PtIV complex, is highly stable and non-toxic if left in the dark but if light falls upon it becomes much less stable and highly toxic to cancer cells. In fact it is between 13 and 80 times more toxic (depending on how and on which cells it is used) to cancer cells than the current platinum based anti-cancer drug Cisplatin. Moreover it kills the cells by a different mechanism of action, so it can also kill cisplatin-resistant cells.

Professor Peter Sadler, Chairman of the Chemistry Department of the University of Warwick, who led the research project said: "Light activation provides its massive toxic power and also allows treatment to be targeted much more accurately against cancer cells."

The compound could be used in particular to treat surface cancers. Patients could be treated in a darkened environment with light directed specifically at cancer cells containing the compound activating the compound’s toxicity and killing those cells. Normal cells exposed to the compound would be protected by keeping the patient in darkness until the compound has passed through and out of the patient.

The new light activated PtIV complex is also more efficient in its toxic action on cancer cells in that, unlike other compounds currently used in photodynamic therapy, it does not require the presence of significant amounts of oxygen within a cancer cell to become toxic. Cancer cells tend to have less oxygen present than normal cells.

Although this work is in its early stages, the researches are hopeful that, in a few years time, the new platinum compound could be used in a new type of photoactivated chemotherapy for cancer.

Même si le travail en est à ses premiers stages, les chercheurs croient que dans quelques années ils pourront utiliser le médicament.

(Nov. 10, 2007) — Combining light-activated cancer drugs with tumour-seeking antibodies could provide a more effective way of treating many cancers, according to new research.

Combiner des médicaments contre le cancer avec des anticorps qui cherchent les tumeurs pourrait s'avérer une thérapie plus efficace pour plusieurs cancers selon une nouvelle recherche.

The study 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.

L'étude décrit comment les scientifiques ont attaché 10 molécules de médicaments activés par la lumière à un anticorps qui reconnait et se niche dans les cellules canécreuses. Les chercheurs ont démontré que cette méthode est plus efficace que si les médciaments n'étaient pas attaché à un anticorps.

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.

PDT (photodynamic therapy) a été démontré plus efficace pour le cancer du de la et de la

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.

Toutefois, la thérapie courante photodynamique était limité parce que les médicaments activés par la lumière ne sont pas capables seuls de cibler spécifiquement les tumeurs. Cela veut dire que le médicament activé par la lumière peuvent circuler dans le corps du patient pour quelque temps après le traitement, laissant les patients sensibles à la lumière ĉe qui pourrrait faire des dommages. L'équipe de chercheurs pensent qu'ils peuvent résoudre ce problème en s'assurant que le médicament va directement aux cellules cancéreuses et n'affectent pas le reste du corps.

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."

"nous avons démontré que c'est possible d'Attacher ces molécules médicamenteuses à des anticorps sans détruire les capacités utiles de ces anticorps . nos résultats sont très prometteurs et nous espérons pouvoir amener cette étude en essais clinique dans un avenir proche. Notre travail étend l,application des PDT à beaucoup de cacners et nous sommes excités de pouvoir amener les PDT en essais cliniques.

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.

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.

La toxicité principale du PDT est la photosensitivité systémis post traitement. L'agent photosensible reste dans le système pour 6 semaines après le traitement dans quelques cas et quand il attteint la peau, les patients peuvent devenir très photosensible à la lumière ambiante même par temps nuageux, ce qui conduit à des coups de soleil.
*Journal article: 'Targeted photodynamic therapy with multiply-loaded recombinant antibody fragments', The International Journal of Cancer, published online 31 October 2007, scheduled for print December 2007.

30.10.2007 16:05



Des chimistes de l'Uni de Neuchâtel, de l'EPFL et du CHUV ont développé une arme contre le cancer. Ils ont combiné un médicament rendant les cellules cancéreuses sensibles à la lumière avec des composés chimiques d'un métal, le ruthénium.

Ces entités ont été synthétisées à l'Institut de chimie de l'Université de Neuchâtel, indique celle-ci mardi dans un communiqué. Les premiers tests biologiques à l'Ecole polytechnique fédérale et au CHUV ont montré d'"excellents résultats" sur des cellules de mélanome.
Potentiel confirmé
Les molécules à base de métaux, en particulier celles issues du platine, sont beaucoup utilisées comme anticancéreux, mais avec un inconvénient de taille: les effets secondaires. Le ruthénium, qui fait partie du même groupe chimique que le platine, semble apporter des solutions à ce problème, notent les chercheurs. Un potentiel confirmé par des études cliniques.

Quant à la lumière, généralement un rayon laser, elle détruit les cellules cancéreuses rendues sensibles à son action par un médicament. Breveté, le nouveau plan d'attaque de l'Université de Neuchâtel, combinant lumière et composés organo-métalliques, permet "d'espérer un jour voir ces produits administrés à des patients", conclut le communiqué.

Apparemment ils ont convoqué une deuxième conférence de presse pour faire baisser les attentes.


Posted: October 30, 2007

LONDON (Reuters) - Using ultraviolet light may one day offer a "double whammy" to kill cancer cells by better focusing antibody-based drugs and triggering the body's own defenses to eliminate tumors, researchers said on Tuesday.

In two studies with mice, a British team cloaked antibodies -- the immune system proteins that tag germs and cancer cells for elimination -- with an organic oil that blocked them from reacting until illuminated with ultraviolet light.

The researchers used engineered immune system proteins called monoclonal antibodies. They are made to home in on proteins known to be overactive in tumor cells.

When the light unblocked the organic coating, the antibodies switched on and attracted killer T-cells to attack the tumor, said Colin Self, a researcher at Newcastle University, who led the studies.

The technique can help prevent damage to healthy tissue because the covered antibodies are dormant in the body unless lit up, Self said.

"What happens in cancer is the body can't mount a response to cure cancer," he said. "This is a way of waking the system up. The antibodies will have their local effect but the hope in all of this is you are bringing in the whole immune system."

So far there are about 20 approved monoclonal antibody-based drugs used to fight cancer and other diseases.

The technique could work with any of these treatments to fight a whole range of cancers, so long as doctors are able to find a way to shine a light on a tumor, Self said.

"You are getting a double whammy," he said. "A stronger effect and you can direct the antibody."

While the studies show promise, the technique is years away for human use and faces a long regulatory road and tough clinical trials before any approval, said David Glover, an independent pharmaceutical consultant.

Même si les études sont prometteuses, la technique est encore à des années d'une utilisation chez les humains et a à passer de difficilles tests avant d'être approuvé, a dit David Glover, un pharmacien indépendant.

"There are a lot of hurdles ahead," Glover told a news conference. "We do not want people to think there is a magic bullet right around the corner.

'Il y a beaucoup d'obstacles devant" a dit GLover dans une nouivelle conférence "nous ne voulons pas que les gens pensent que nous avons la balle magique très proche de nous."

The next step is initial clinical trials in skin cancer patients, which Self said he hoped to begin early in 2008, provided he could find funding for the research.

La prochaine étape ce sont les essais chez les personnes ayant le cancer de la ce que Self dit espérer début 2008 s'il peut trouver des fonds.

Scientists at Newcastle University have developed a cancer fighting technology which uses UV light to activate antibodies which very specifically attack tumours.

Les scientifiques ont développé une nouvelle technologie qui utilise la lumière UV pour activer des anticorps qui attaquent très spécifiquement des tumeurs.

Therapeutic antibodies have long been recognised as having excellent potential but getting them to efficiently target tumour cells has proved to be very difficult.

Les anticorps thérapeuthiques ont longtemps été reconnu pour avoir un excellent potentiel mais les employer à cibler spécifiquement les tumeurs cancéreuses a été prouvé être très difficille.

Now, Professor Colin Self and Dr Stephen Thompson from Newcastle University have developed a procedure to cloak antibodies which can then be activated by UV-A light and so can be targeted to a specific area of the body just by shining a probe at the relevant part.

Les chercheurs ont développé une procédure pour confiner les anticorps qui peuvent être activer par les rayons uv-a et ainsi peuvent être activer à certains endroits du corps en éclairant les régions voulues.

This procedure maximizes the destruction of the tumour while minimising damage to healthy tissue.

Cette procédure maximise la destruction des cellules cancéreuses et épargne les tisssus sains.

Professor Self says, "I would describe this development as the equivalent of ultra-specific magic bullets. This could mean that a patient coming in for treatment of bladder cancer would receive an injection of the cloaked antibodies. She would sit in the waiting room for an hour and then come back in for treatment by light. Just a few minutes of the light therapy directed at the region of the tumour would activate the T-cells causing her body's own immune system to attack the tumour."

Le professeur Self a dit "Je décrirais ce développement comme l'équivalent d'une balle magique ultra-spécifique. Cela voudrait dire qu'un patient pourrait venir un traitement du cancer de la vessie, recevoir une injection, attendre une heure et revenir pour le traitement avec la lumière.

Un traitement avec la lumi;re de quelques minutes suffirait à activer le médicament et les cellules-T qui attaqueraient la tumeur.


The details are contained in two papers* published online in the journal ChemMedChem.

The Newcastle University researchers demonstrate in the first paper the procedure of coating the surface of a protein, such as an antibody, with an organic oil which is photocleavable, a process called "cloaking". This prevents the antibody reacting within the body unless it is illuminated.

When UV-A light is shone onto the cloaked antibody it is activated. The activated antibody binds to T-cells, the body's own defence system, triggering the T-cells to target the surrounding tissue.

In the second paper, they demonstrate that when the cloaked antibodies are activated by light near a tumour, the tumour is killed. This work means that antibodies can be targeted to kill cancer tumours with much greater specificity giving fewer side effects.

These cloaked antibodies can be used alone, or in conjunction with the many antibodies already produced against a wide variety of cancers as bispecific complexes. These complexes are formed from two antibodies, one antibody binds to a tumour marker, the other with a T-cell. The T-cell binding end remains inactive until re-activated by light. This means when the bispecific antibody binds to healthy tissues away from light, it cannot activate T-cells, resulting in far fewer side effects.

Professor Self says, "This opens up so many possible applications for example, for patients who are undergoing surgery for prostate cancer. After the surgeon has removed the bulk of a tumour, the patient could then be injected with bispecific antibodies and a light shone at the affected area which would target the patient's own immune system to the tumour site."

"Cela ouvre beaucoup de possibilités d'applications par exemple, pour les patients qui subissent une chirurgie de la prostate, après que le chirurgien a enlevé la grosse partie de la tumeur, le patient pourrait être injecté avec des anticorps et une lumière pourrait être appliqué à la région spécifique ce qui amènerait le système immunitaire à réagir sur le site de la tumeur.

"This is therefore a very specific treatment and while our work indicates that sunlight doesn't activate these antibodies, patients may have to be advised to avoid direct sunlight for a short period after treatment."

A key challenge facing doctors as they treat patients suffering from cancer or other diseases resulting from genetic mutations is that the drugs at their disposal often don't discriminate between healthy cells and dangerous ones -- think of the brute-force approach of chemotherapy, for instance. To address this challenge, Florida State University researchers are investigating techniques for using certain molecules that, when exposed to light, will kill only the harmful cells.

Le défi auquel les docteurs font face lorsqu'ils traitent des patients souffrant du cancer ou d'autres maladies c'est que les médicaments à leur disposition ne discriment pas entre les cellules malades et saines.
Pensez à la force brutale de la chimiothérapie par exemple. Pour répondre à ce défi, les chercheurs cherchent des techniques pour utiliser certaines molécules qui, lorsqu'exposer è la lumière s'attaquera seulement aux cellules cancéreuses.

Igor V. Alabugin is an associate professor of chemistry and biochemistry at FSU. He specializes in a branch of chemistry known as photochemistry, in which the interactions between atoms, small molecules and light are analyzed.

Igor V. Alabugin est un professeur associé de chimi et de biochimie à l'université de Floride. Il se spécialise dans une branche de la chimie connu comme la photothérapie dans laquelle les interactions entre les atomes, les petites molécules et la lumière sont analysées.

"When one of the two strands of our cellular DNA is broken, intricate cell machinery is mobilized to repair the damage," he said. "Only because this process is efficient can humans function in an environment full of ultraviolet irradiation, heavy metals and other factors that constantly damage our cells."

"Quand un de deux bouts de notre ADN est brisé, la machinerie de la cellule est mobilisé pour réparer ce dommage." dit-il " Seulement parce que ce processus est efficace, est-ce que ça veut dire que les humains peuvent fonctionner dans un environnement rempli d'ultraviolet, de métaux lourds et de d'autres facteurs qui endommagent constamment leurs cellules."

However, a cell that sustains so much damage that both DNA strands are broken at the same time eventually will commit suicide -- a process known as apoptosis.

Toutefois, une cellule qui subit tant de dommages que les deux bouts d'ADN seront brisé en même temps commettra éventuellement le suicide, un procesus connu sous le nom d'apoptosis.


"In our research, we're working on ways to induce apoptosis in cancer cells -- or any cells that have harmful genetic mutations -- by damaging both of their DNA strands," Alabugin said. "We have found that a group of cancer-killing molecules known as lysine conjugates can identify a damaged spot, or 'cleavage,' in a single strand of DNA and then induce cleavage on the DNA strand opposite the damage site. This 'double cleavage' of the DNA is very difficult for the cell to repair and typically leads to apoptosis."

"Dans notre recherche, nous travaillons sur des moyens pour induire l'apoptose dans les cellules cancéreuses -ou n'importe quelle cellule qui a subit des dommags génétics - en endommageant les deux bouts de l'ADN"
dit Alabugin " Nous avons trouvé qu'un groupe de molécules tuant le cancer connu sous le nom de lysine peut identifier un point endommagé dans un des brins de l'Adn et le répliquer sur l'autre brin. Ce double endommagement est très difficile à réparer pour la cellule et conduit à l'apoptose.

What's more, the lysine conjugates' cancer-killing properties are manifested only when they are exposed to certain types of light, thus allowing researchers to activate them at exactly the right place and time, when their concentration is high inside of the cancer cells, Alabugin said.

Ce qui est plus c'est que les propriétés de la lysine (lysine conjugate) sont manifestes seulement lorsqu'exposé à un certain type de lumière, ce qui permet aux chercheurs de les activer seulement à la bonne place et au bon moment, quand leur concentration est élevé dans les cellules cancéreuses

"So, for example, doctors treating a patient with an esophageal tumor might first inject the tumor with a drug containing lysine conjugates," he said. "Then they would insert a fiber-optic scope down the patient's throat to shine light on the affected area." The light exposure would activate the drug, leading to double-strand DNA damage in the cancerous cells -- and cell death -- for as much as 25 percent to 30 percent of the cells in the tumor,at a rate that rivals in efficiency any of the highly complex and rare DNA-cleaving molecules produced by nature, Alabugin said -- and, perhaps just as importantly, avoids damage to healthy cells.

Par exemple pour un cancer de l'oesophage, le docteur peut dans un premier temps injecté la tumeur avec le médicament contenant le lysine conjugate et après il introduit une fibre optique au travers la gorge du patient jusqu'à la tumeur et il envoir la lumière sur la tumeur. La lumière active le médicament, conduit au double domamge des cellules concernées et la mort cellulaire intervient pour 25 ou 30% de ces cellules dans la tumeur. et ce qui est plus important n'endommage pas les cellules saines.

For tumors located deeper within the body, he pointed to other studies showing that a pulsed laser device can be used to penetrate muscle and other tissues, thereby activating the drugs using near-infrared beams of light.

Pour des tumeurs localisé plus profondément dans le corps, le docteur a parlé de d'autres études montrant qu'un instrument à lazer pulsé peut pénétrer les muscles et les autres tissus et activer les médicaments par la lumière.

As proof of principle to the idea that lysine conjugates possess anti-cancer activity, Alabugin collaborated with cancer biologist Dr. John A. Copland of the Mayo Clinic College of Medicine in Jacksonville, Fla. In their tests, several of the molecules demonstrated little effect upon cultured cancer cells -- in this case, metastatic human kidney cancer cells -- without light, but upon phototherapy activation killed more than 90 percent of the cancer cells with a single treatment. Future work will include demonstrating anti-cancer activity in an animal model. Successful completion of the preclinical studies then could lead to clinical trials with human patients.

Comme preuve du principe de l'idée que la lysine conjugée pssède une activité anti-cancer, Alagugin collabore avec le biologiste Copland de la clinique Mayo. Dans leur test, plusieurs de ces molécules démontrent un petit effet sur les cellules en culture -dans le cas c'était des cellules de cancer du rein - sans la lumière mais avec l'activiation par la photothérapie, plus de 90% des cellules cancéreuses ont été tués par un seul traitement. De futurs travaux inclueront une démonstration sur un modèle animal. Les succès de ces études pré-cliniques pourraient conduire à des essais sur des patients humains

Alabugin recently collaborated with four other FSU researchers -- Associate Professor of Chemistry and Biochemistry Nancy L. Greenbaum and her postdoctoral fellow, Jörg C. Schlatterer, as well as Alabugin's postdoctoral fellow, Serguei V. Kovalenko, and doctoral student Boris Breiner -- on a paper describing the results of their research. That paper, "DNA Damage-Site Recognition by Lysine Conjugates," was published in the July 23 issue of the Proceedings of the National Academy of Sciences.

Alabugin and his FSU colleagues also have applied for a patent on their work.

Tookad, un médicament activé par la lumière, a démontré qu'il pouvait réduire les tumeurs de la prostate de 84% et dans 46% des cas supprimé le cancer. La thérapie photodynamique est basé sur un médicament anti-cancer qui devient toxique quand il est exposé à la lumière. Le médicament est injecté dans le sang et une fois qu'il a atteint la cible, les médecins font briller une lumière sur la tumeur en utilisant une fibre optique inséré par un cathéthère. Le médicament détruit les vaisseaux illuminés, annihilant l'apport de sang et affamant et faisant ainsi disparaitre la tumeur sans endommagé les tissus sains autour.  


Cette thérapie a été développé par Avigdor Scherz et Yoram Solomon, biochimistes à l'institut de Weizman en Israël. Scherz explique que le processus est le même que le processus qui a lieu dans une plante avec la cholorophylle. Les chercheurs croient que si Tookad continues a remplir ses promesses dans les essais cliniques, ça pourrait être un moyen efficace de traiter les tumeurs cancéreuses sans avoir recours à la chirurgie. Il y a présentement des patients demandeurs pour la phase III d'essais clinique.

Tookad en hébreux signifie la chaleur de la lumière.