Читать книгу Advances in Radiation Therapy - Группа авторов - Страница 25

The tumour microenvironment engages different tumour-suppressive mechanisms, which might even be more pronounced after irradiation. Immunocytokines are able to overcome this immunosuppression and have shown antitumour effects, also in combination with irradiation. IL-2-based immunocytokines evaluated in combination with irradiation are L19-IL2 and NHS-IL2. L19-IL2 targets the tumour neovasculature and has shown antitumour effects in combination with irradiation preclinically [86, 87], even in an MHC-I-deficient cancer model [88]. NHS-IL2, targeting tumour necrosis by binding to extracellular DNA-histone complexes, achieved synergistic antitumour activity with irradiation preclinically and in a phase Ib study [89]. NHS-IL12 has shown antitumour activity on its own [90, 91] and in combination with different anticancer treatments [42]. Irradiation has been shown to increase intratumoural bioavailability of the construct [92] and to synergise with NHS-IL12 for antitumour activity and abscopal effects [97].

Table 1. Different classes of immunotherapies already utilised in combination with radiotherapy in clinical trials according to Golden et al. [96], with an explanation of the mode of action