Abstract
Tumor-targeting monoclonal antibodies (mAbs) are now widely used for the treatment of cancer patients and their numbers are constantly increasing. Over the past ten years, numerous studies have demonstrated that the anti-tumor role of these antibodies far exceeds that of passive therapies as it was initially described, with the possibility of recruiting innate immune cells to promote activation of the early stages of immune response and to generate a long-term protective anti-tumor memory immune response. Understanding these mechanisms has recently led to the clinical development of a new generation of anti-tumor antibodies modified to increase their ability to interact with immune cells. Finally, the first preclinical and clinical studies have recently demonstrated the interest of developing therapeutic combinations combining anti-tumor mAbs with immune-, chemo- or radiotherapy, to reinforce their immunomodulatory potential and ensure effective and durable anti-tumor protection.
Highlights
Des essais cliniques sont en cours, associant différentes chimiothérapies avec un AcM anti-Her2/neu, le trastuzumab et un AcM anti-EGFR, le pertuzumab, dans les cancers gastriques et œsophagiens (NCT02205047 ; NCT02120911), urothéliaux (NCT02006667), de l’ovaire (NCT02004093) ou du poumon non à petites cellules (NCT02226757)
Ces deux inhibiteurs de points de contrôle immunitaire, ainsi que de nouveaux AcM bloquants, voient leur utilisation en clinique s’étendre désormais à de nombreux types de cancers, ouvrant des perspectives intéressantes afin de lever les résistances aux immunothérapies par des AcM anti-tumoraux
Over the past ten years, numerous studies have demonstrated that the anti-tumor role of these antibodies far exceeds that of passive therapies as it was initially described, with the possibility of recruiting innate immune cells to promote activation of the early stages of immune response and to generate a long-term protective antitumor memory immune response
Summary
Alors que, dans un modèle de cancer colorectal, le traitement par l’anticorps anti-EGFR, le cétuximab, ou par une chimiothérapie ont peu d’impact sur la réponse immunitaire anti-tumorale suite à la mort de la cellule tumorale, leur combinaison thérapeutique déclenche une mort cellulaire immunogénique se traduisant par une phagocytose plus active et un recrutement de lymphocytes T spécifiques [33]. L’importance de l’association radiothérapie/anti-CD20 a également été montrée par une étude dans laquelle le traitement par radiothérapie de cellules de lymphomes augmente l’efficacité thérapeutique d’un AcM [34].
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