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

Nicolle H. Rekers, Veronica Olivo Pimentel, Ala Yaromina, Natasja G. Lieuwes, Rianne Biemans, Catharina M. L. Zegers, Wilfred T. V. Germeraad, Evert J. Van Limbergen, Dario Neri, Ludwig J. Dubois*, Philippe Lambin

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

29 Citations (Web of Science)

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 languageEnglish
Article numbere1414119
Number of pages15
JournalOncoImmunology
Volume7
Issue number4
DOIs
Publication statusPublished - 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

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