The advancement in basic life sciences has indicated the details of complexity of disease, the existing treatments of cancer, are not at all meeting the expectations of the patients. The chemotherapy and radiotherapy although effective they are unable spare the normal tissue and hence carry a high burden of toxicity as they are not targeted in their actions. Monoclonal antibodies although targeted, they are highly expensive and less effective. In order to improve their efficacy, application of laser has made leap advancement in therapeutics. Light activated antibodies are therapeutic antibodies which are activated by irradiation since they have high cytotoxic potency this making them more target specific (tumour). Therapeutic antibodies have unwanted and cross reactivity reactions that can cause circulatory persistence and target fidelity. This determines whether a therapeutic antibody has an acceptable level of side effects. Most anticancer drugs used during treatment lack tumour selectivity and are not useful in medicine as monoclonal antibodies that bind to specific markers on the surface of tumour cells providing an alternative therapy involving tumour specificity and thus less toxic. Monoclonal antibodies are more specific as they are made of identical immune cells and have a single specific affinity to bind to the same epitope. Thus, in cancer, monoclonal antibodies bind to cancer specific antigens (receptors) and induce an immunological response against the targeted cancer cells. The research of the light activated antibodies for cancer treatment has proven to be extremely successful and has made monumental strikes, towards reaching human trials. Many companies have based their reaches in this field such as:
• Absci – Portland-based company which develops and produces monoclonal antibodies
• Fabion Pharmaceuticals – start up focusing on developing bispecific antibodies for cancer treatments
• Seattle Genetics – monoclonal antibodies for cancer treatment.
The therapeutic and commercial successes made by Rituximals, Trastozumab, Cetuximal and other mAbs have inspired the engineers to improve the efficacy of these molecules.
Specificity enhancement requires positive focus on the tumour site to maximize the toxicity only to cancerous tissues. Photo-thermal and photodynamic therapies have promising localizing procedures as they both use laser light to target treatment to tumours. Light has specific wavelength and is focused in a narrow beam and creates a very high intensity light. Since lasers can focus precisely for cutting through tissues during surgery. Laser therapy uses high intensity light to treat cancer and other illness. It is used to shrink or destroy tumours of precancerous growth. They are normally used to treat superficial cancer such as basal cells skin cancer. Laser also can be used to relief certain symptoms of cancer such as bleeding or obstruction. Laser therapy is often combined with other treatments such as surgery or chemotherapy. Lasers seal the nerve endings to reduce pain after surgery and seal vessels to reduce swelling and limit the spread of tumour cells. Localized laser illumination with specific wavelength cause cytotoxic heating which may affect the adjacent normal tissues. This damage was further reduced by linking the dyes to tumour targeting antibodies. The laser therapy is often given through a flexible endoscope. The endoscope is fitted with optical fibres and is inserted through an opening in the body such as mouth, nose, anus or vagina.
Photodynamic therapy
In photodynamic therapy, a drug called photo sensitizer or photo-sensitizing agent is injected into a patient and absorbed by the cell all over the body. Laser light is then used to activate the agent and destroy cancer cells. Laser therapies being one of the advancements in specific targeting of antibodies towards cancer infected cells. There have been other advancements such as the second type of targeting is by cancer targeting antibodies are directly linked to a toxin. In this type, the antitumour antibodies are reversibly inhibited unless it is illuminated. The cancer targeting antibodies are free to target cancer cells but the toxic part of the molecule remains inactive until irradiated. This is more specific with light mediated targeting added to the tumour antigen thus, normal tissues are not affected because the toxic portion is inactive. The third type of targeting is by antibodies involving monoclonal antibodies which only bind to cancer cell specific antigen, and induce an immunological response. Such monoclonal antibodies can be modified to design bispecific antibodies that can bind with their F antibodies. Antibodies directed enzyme product therapy (ADEPT) can also gain from the beneficial effect of photo-reversible inactivation. After antibody treatment, enzyme can be administered but are capable of binding to tumour tissues only in the regions that have been illuminated. The final type of targeting is by antibodies which re-target the patient’s own immune-regulatory cells directly to the surface of the tumour. The patient’s own immune-regulatory cells are used to attack tumour. The conjugate binds to the tumour and the T-cells, hence targeting the T-cells to the tumour. When a UV light is shown on the T-antibodies which are coated with organic oil, is activated. The activated antibodies bind to the tumour, triggering the body’s own defense system to produce more T-cells and surround the infected tissue and kill the tumour. This work means that antibodies can be targeted to kill cancer tumour with much greater specificity giving fewer side effects.
The biggest and greatest army to fight a war against various diseases within our body is our immune system. In clinical trials, doctors are using lasers to treat cancers of the brain and prostate, among others. The mode of delivery of the light is considered because they may have limited tissue penetration property. Light emitting optical fibre probes can be deployed to many areas of the body. Laser therapy also has several limitations such as surgeons must have specialized training before they can use the laser during the therapy. Strict safety precautions have to follow by the surgeon. Laser therapy is expensive and requires bulky equipment. The effect of laser therapy may not last long, thus doctors may have to repeat the treatment for a patient to get the full benefit. Every human and technological creation has their pros and cons. But when we look at the pros of laser therapy, we see that lasers are more precise that standard tools (scalpels) as they do less damage to the normal tissues surrounding the affected ones. As a result, patients usually have less pain, bleeding, swelling and scarring. With laser therapy operations are usually short. In fact, laser therapy can often be done on an outpatient basis. It takes less time for patient to heal after surgery and they are less likely to get infections.
We believe that with the growth in research along with high and advanced developments of machines and increased growth in technology, impossible things become possible in medicine. The photo-activation technology is the biggest boom in improving the targeting of therapeutic conjugates to tumours by increasing their effective specificity.
(Authors are with Manipal College of Pharmaceutical Sciences, Manipal, Karnataka 576 104)