|
|
RADIOIMMUNOTHERAPY: THE AVIDIN BIOTIN TECHNIQUE
Radioimmunotherapy is the treatment of cancer through antibodies tagged with “intelligent” radiation, which target the malignant cells while avoiding healthy cells.
However, its full application has been slowed by the problem of so-called “dispersed antibodies”, i.e. those radioactive proteins which do not succeed in reaching the target tumour.
IEO researchers therefore had the idea of tagging antibodies with radioactivity at a second stage, once the “dispersed” antibodies have already left the organism. They designed a technique called avidin-biotin, which enables radioactive tagging only of those antibodies positioned on the tumour.
The cancers that are most sensitive to this treatment are brain tumours, especially glioblastoma, and ovarian cancer. |
 |
Conventional Radioimmunotherapy
Until recently, radioimmunotherapy was based on the direct administration of radioactive monoclonal antibodies. Monoclonal antibodies, refined with hybridoma and genetic engineering techniques, have the same properties as normal antibodies produced by the immune system: they recognise specific proteins (antigens) in the tumour. With the availability of dozens of monoclonal antibodies, each capable of recognising specific cancer antigens, it has been possible to use them to transport a radioactive substance able to destroy the cancer cell. |
| Il limite della metodica è rappresentato dal fatto che l'anticorpo marcato si lega al tumore solo in una piccola percentuale (circa l'uno per cento), mentre la maggior parte degli anticorpi continua a circolare nel sangue e finisce per disperdersi nell'organismo, accumulando radiazioni nei tessuti sani, in particolare nel rene, nel fegato e nel midollo osseo, dove possono creare danni. Avendo a disposizione decine di anticorpi monoclonali, ognuno capace di riconoscere specifici antigeni tumorali, è stato possibile utilizzarli per trasportare un agente radioattivo capace di distruggere la cellula tumorale. Il limite della metodica è rappresentato dal fatto che l'anticorpo marcato si lega al tumore solo in una piccola percentuale (circa l'uno per cento), mentre la maggior parte degli anticorpi continua a circolare nel sangue e finisce per disperdersi nell'organismo, accumulando radiazioni nei tessuti sani, in particolare nel rene, nel fegato e nel midollo osseo, dove possono creare danni. |
The new radioimmunotherapy technique with AVIDIN-BIOTIN
The Milan-based European Institute of Oncology succeeded in designing and refining a system able to prevent the dispersion of radioactive antibodies. As with conventional radioimmunotherapy, pretargeting is based on the use of monoclonal antibodies. However, in this technique they are made radioactive only after they have reached their destination and any dispersed antibodies have been eliminated. In fact, once injected, monoclonal antibodies collect in the tumour over about 24-48 hours and remain there for another 3-5 days, while the dose dispersed in other organs is eliminated in the urine in 2-3 days.
To carry the radioactive agent to the tumour, Dr. Paganelli designed a system exploiting the natural attraction between two molecules, avidin and biotin, i.e. Vitamin H. Avidin is a protein present in egg white and forms a close bond with four biotin molecules.
|
3-STEP-PRETARGETING with AVIDIN-BIOTIN
The therapeutic regimen of the new radioimmunotherapy technique involves three phases: |
 |
First Phase
On the first day, the patient receives an endovenous injection of monoclonal antibodies previously bonded to biotin molecules. These antibodies accumulate at their target (the tumour) over 24-48 hours. |
 |
Second Phase
24-48 hours after the first administration, the patient receives another endovenous infusion, this time of avidin: thanks to the strong attraction between the two molecules, the avidin bonds to the biotin already present at the tumour, while any remaining in circulation is metabolised by the liver. Avidin has 4 bond sites in which further biotin molecules can be inserted. |
 |
Third Phase
On the third day, when the antibodies not bonded to the tumour have been eliminated, the patient receives the last injection, this time of biotin previously labelled with a radioactive isotope. The radioactive biotin is then attracted to the avidin in the tumour, and reaches its specific target in just a few minutes, causing its destruction. The radioactive biotin not bonded to the tumour is quickly eliminated through the kidneys.
Results |
Results
To date, this type of immunotherapy has been applied only in cases of severe, advanced stage cancers, after other therapies have proved ineffective. The most sensitive tumours to this therapy are brain tumours, ovarian cancer and lymphomas. Although the treatment was well tolerated and free of the side effects found with traditional therapies, it must be stressed that this is still an experimental therapy, indicated only for certain types of neoplasia and only when the tumour does not exceed 2-3 cm in diameter.
The avidin-biotin pretargeting system is a highly promising targeted radioimmunotherapy model for cancer treatment. In theory, it can be applied to all types of tumours that have specific antibodies. Although complex, the system is not difficult to use. However, it does require facilities suitable for the use of radioisotopes.
|
|
