Melanoma is a type of skin cancer that can spread quickly to other parts of the body, making it difficult to treat. Traditional treatments such as chemotherapy and radiation have only limited success in treating advanced melanoma.
More recently, immune checkpoint inhibitors (ICI), a type of cancer immunotherapy, have revolutionized the treatment of advanced melanoma by unleashing the power of the immune system to attack cancer cells. But ICI therapy does not work for all patients, possibly due to the lack of pre-existing antitumor immunity or acquired tumor resistance.
Joining Forces
“Analyses by our group and others have shown that the development of auto-immune skin depigmentation - or vitiligo - during immunotherapy was significantly associated with prolonged survival of advanced melanoma patients,” says Rosalie Luiten, professor of Experimental Dermatology.
Based on that observation, the group developed MI therapy. MI therapy combines the vitiligo- inducing agent monobenzone with imiquimod, which induces melanoma-specific immunity and melanoma regression in preclinical models and patients. This project will translate these (pre)clinical findings further to the clinic by combining the expertise of oncologists Dr. Mariette Labots and Prof. Fons van den Eertwegh, with immunologists Prof. Rosalie Luiten and Prof. Tanja de Gruijl, head of the Immunotherapy Lab of the Department of Medical Oncology, at Cancer Center Amsterdam, as well as collaborators in participating centers NKI-AVL and LUMC.
resistance to immunotherapy in patients with melanoma.
Paving the path for clinical application
The funded project will test MI therapy in combination with ICI.
“We think that MI therapy may potentiate immunotherapy and contribute to overcoming resistance in patients with melanoma,” says Dr. Labots. “By adding MI therapy to ICI, we will induce specific anti-melanoma immunity, which will be amplified by immune checkpoint inhibitors. So MI therapy can be a potentiator of ICI efficacy in melanoma patients to improve the clinical benefit.”
Preliminary work by the Luiten group has shown that MI therapy alone is a low-cost, broadly applicable, and well-tolerated treatment that induces local and systemic anti-melanoma immunity and local tumor regression.
The phase Ib clinical study will assess the safety and tolerability of the combination of ICI with MI therapy, in addition to determining the maximum tolerated dose. The results are expected to provide proof of principle for a subsequent Phase II efficacy evaluation in patients with melanoma metastases.
For more information contact: Dr. Mariette Labots or Prof. Rosalie Luiten.
Main applicants and departments
1. Clinical researchers: Mariette Labots, Fons van den Eertwegh, Amsterdam UMC, Department of Medical Oncology
2. Pre-clinical/translational researchers: Rosalie Luiten, Department of Dermatology and Tanja de Gruijl, Department of Medical Oncology
Title project:
ImmunizeMI: A Phase I/II study of combined monobenzone/imiquimod therapy and immune checkpoint inhibition in patients with cutaneous melanoma metastases.
Funding provided by:
Cancer Center Amsterdam Foundation
The second Cancer Center Amsterdam Foundation funded Proof of Concept (PoC) / Proof of Principle (PoP) project will be highlighted later this month.
Text by Laura Roy.
This article was created for Cancer Center Amsterdam.
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