IMoST - Melanoma targeted radionuclide therapy: effects on antitumor immune response and therapeutic strategies of combination

Published on June 8, 2021 – Updated on October 26, 2021

We study the effects of the melanoma targeted radionuclide therapy on the antitumoral immune response, using [131I]ICF01012 in monotherapy and combined with immune checkpoint inhibitors.

SPECT/CT imaging of melanoma-bearing mice, after [131I]ICF01012 injection.

SPECT/CT imaging of melanoma-bearing mice, after [131I]ICF01012 injection.

Targeted radionuclide therapy (TRT) consists in addressing a radionuclide to tumour cells by targeting, with a vector, their specific properties. Our team has been working on this strategy for 15 years with the molecule [131I]ICF01012. [131I]ICF01012 is a benzamide derivative which targets melanin, a small compound produced in melanoma, a particularly aggressive form of skin cancer. We have previously shown that systemic intravenous injection of [131I]ICF01012 decreased tumour volume and increased survival in mouse models, with moderate toxicity especially in hyperpigmented pejorative models. These preclinical studies resulted in a Phase I clinical trial, MELRIV1, which has been open since July 2019 (NCT03784625).

Since 2010, management of metastatic melanoma has been revolutionized by two strategies: therapies targeting the MAP-Kinases pathway and immunotherapy (IT, immune checkpoint inhibitors CTLA-4 and PD-1/PD-L1). However, the lack of response of certain tumors or the frequent occurrence of incomplete responses leading to a stabilization of the disease under treatment requires the development of new combination strategies.

Since TRT modifies the antitumoral immune response, the combination of TRT with IT is of major interest: the effects on TRT on immunity could significantly increase the effectiveness of IT. We will test this hypothesis by combining immune checkpoint inhibitors with TRT. Our team studies the effects of our molecule, [131I]ICF01012, on the antitumoral immune response particularly in terms of immune infiltrate, abscopal effect and immunogenic death.

This characterization of the effects of TRT on immunity should support the rationale for an association of TRT with IT in a future clinical trial.

Other partners within the GCCA

  • Clermont-Ferrand University Hospital- Dermatology and Cutaneous Oncology Department
  • Jean PERRIN Comprehensive Cancer Center- Nuclear Medicine Department
  • Jean PERRIN Comprehensive Cancer Center - CIRMEN : Center for Innovation and Research in Nuclear Medicine