Les anticorps radiomarqués pour le traitement des cancers

Abstract

Les anticorps radiomarqués ont maintenant fait leurs preuves dans le traitement des lymphomes malins non hodgkiniens de phénotype lymphocytaire B. D’autres maladies cancéreuses s’avèrent plus difficiles à traiter, que les cellules soient trop dispersées pour un traitement avec un émetteur de particules β- peu efficaces contre des cellules isolées (cas des leucémies par exemple) ou que ces cellules, comme dans la plupart des tumeurs solides, soient radiorésistantes. Des approches nouvelles, préciblage, utilisation d’atomes émetteurs de particules α ou d’électrons Auger sont en passe d’apporter des solutions convaincantes et la radio-immunothérapie devrait trouver sa place dans une approche rationnelle du traitement des cancers.

The first treatment ever by radio-immunotherapy (RIT) was performed by William H. Beierwaltes in 1951 and was a success. Fifty years later, the main question is to find ways of extending the success of radiolabelled anti- CD20 antibodies in indolent non-Hodgkin’s lymphoma to other forms of cancer. Solid tumours are much more radioresistant than lymphomas, but they respond to RIT if the lesions are small. Clinical situations of residual or minimal disease are thus the most likely to benefit from RIT in the adjuvant or consolidation settings. For disseminated disease, like leukemias or myelomas, the problem is different: beta– particles emitted by the radioactive atoms classically used for cancer treatment (iodine-131 or yttrium-90) disperse their energy in large volumes (ranges 1 mm to 1 cm) and are not very effective against isolated cells. Advances in RIT progress in two directions. One is the development of pretargeting strategies in which the antibody is not labelled but used to provide binding sites to small molecular weight radioactivity vectors (biotin, haptens). These techniques have been shown to increase tumour to non-target uptake ratios and anti-tumour efficacy has been demonstrated in the clinic. The other approach is the use of radionuclides adapted to the various clinical situations. Lutetium-177 or copper-67, because of the lower energy of their emission, their relatively long half-life and good gamma emission, may significantly improve RIT efficacy and acceptability. Beyond that, radionuclides emitting particles such as alpha particles or Auger electrons, much more efficient to kill isolated tumour cells, are being tested for RIT in the clinic. Finally, RIT should be integrated with other cancer treatment approaches in multimodality protocols. Thus RIT, now a mature technology, should enter a phase of well designed and focused clinical developments that may be expected to afford significant therapeutic advances.