Abstract
Recently, we have shown that the administration of the tumour-targeted antibody-based immunocytokine L19-IL2 after radiotherapy (RT) resulted in synergistic anti-tumour effect. Here we show that RT and L19-IL2 can activate a curative abscopal effect, with a long-lasting immunological memory. Ionizing radiation (single dose of 15Gy, 5 x 2Gy or 5 x 5Gy) was delivered to primary C51 colon tumour-bearing immunocompetent mice in combination with L19-IL2 and response of secondary non-irradiated C51 or CT26 colon tumours was evaluated. 15Gy + L19-IL2 triggered a curative (20%) abscopal effect, which was T cell dependent. Moreover, 10Gy + L19-IL2 treated and cured mice were re-injected after 150 days with C51 tumour cells and tumour uptake was assessed. Age-matched controls (matrigel injected mice treated with 10Gy + L19-IL2, mice cured after treatment with surgery + L19-IL2 and mice cured after high dose RT 40Gy + vehicle) were included. Several immunological parameters in blood, tumours, lymph nodes and spleens were investigated. Treatment with 10Gy + L19-IL2 resulted in long-lasting immunological memory, associated with CD44(+)CD127(+) expression on circulating T cells. This combination treatment can induce long-lasting curative abscopal responses, and therefore it has also great potential for treatment of metastatic disease. Preclinical findings have led to the initiation of a phase I clinical trial (NCT02086721) in our institute investigating stereotactic ablative radiotherapy with L19-IL2 in patients with oligometastatic solid tumours.
Original language | English |
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Article number | e1414119 |
Number of pages | 15 |
Journal | OncoImmunology |
Volume | 7 |
Issue number | 4 |
DOIs | |
Publication status | Published - 1 Jan 2018 |
Keywords
- abscopal effect
- immunotherapy
- memory effect
- L19-IL2
- Radiotherapy
- tumour
- RENAL-CELL CARCINOMA
- ED-B DOMAIN
- T-CELLS
- CANCER-IMMUNOTHERAPY
- SELECTIVE EXPRESSION
- METASTATIC MELANOMA
- ABSCOPAL REGRESSION
- LOCAL RADIOTHERAPY
- RADIATION-THERAPY
- CTLA-4 BLOCKADE