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Oncoimmunology. 2018 Jan 16;7(4):e1414119. doi: 10.1080/2162402X.2017.1414119. eCollection 2018.

The immunocytokine L19-IL2: An interplay between radiotherapy and long-lasting systemic anti-tumour immune responses.

Author information

1
Department of Radiotherapy, The M-Lab group, GROW - School for Oncology and Developmental Biology, Maastricht Comprehensive Cancer Centre, Maastricht University Medical Centre, Maastricht, The Netherlands.
2
Department of Internal Medicine, Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht Comprehensive Cancer Centre, Maastricht University Medical Centre, Maastricht, The Netherlands.
3
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Zürich, Switzerland.
4
Department of Radiotherapy, The D-Lab, GROW - School for Oncology and Developmental Biology, Maastricht Comprehensive Cancer Center, Maastricht University Medical Center, Maastricht, The Netherlands.

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 × 2Gy or 5 × 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.

KEYWORDS:

L19-IL2; Radiotherapy; abscopal effect; immunotherapy; memory effect; tumour

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