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Dendritic cells can initiate an immune response against tumor cells by activating T cells. In patients diagnosed with cancer this mechanism of immune surveillance was insufficient to prevent tumor outgrowth. To boost a strong immune response against tumor cells in cancer patients, dendritic cell treatment was optimized over the past decades at the department of Tumor Immunology (currently department of Medical Biosciences), headed by Carl Figdor and Jolanda de Vries.
For dendritic cell treatment, dendritic cells are isolated from the blood of patients, trained in the laboratory to recognize melanoma cells, activated and injected back into the patient with the aim to activate immune responses against tumor cells. After promising results in small clinical trials, a randomized clinical trial investigating dendritic cell treatment in patients with localized melanoma was initiated in 2016. The MIND-DC trial was a combined effort of over 30 people from the Radboudumc departments of Medical Biosciences, Medical Oncology, Pharmacy, Dermatology, Hematology, Surgical Oncology and Medical Imaging and in collaboration with the Isala Hospital. The trial was funded with by the Dutch health insurance.
The trial was stopped prematurely as a standard of care treatment with another form of immunotherapy, immune checkpoint inhibition, became available. Still, clear conclusions could be drawn from the inclusion of 148 eligible patients. First, the clinical trial confirmed the safety of dendritic cell treatment with very few patients (5%) having severe side effects. Second, dendritic cell treatment could induce immune responses against melanoma cells in the majority of patients (67%). Unfortunately, the induced immune responses did not translate into clinical benefit.
In collaboration with Laurence Zitvogel, Gustave Roussy Cancer Campus in France, stool samples were analysed to map the microbes in the gut, called microbiota. The data show that there is a relation between the gut microbiota and the clinical outcome of the patients. Further translational research on patient samples is ongoing. We expect to obtain more insight in the prognostic and predictive value of the blood, detected immune responses and microbiome.
The MIND-DC team, led by Gerty Schreibelt and Jolanda de Vries of the department of Medical Biosciences and in collaboration with Kalijn Bol of the department of Medical Oncology, published the results of the clinical trial in Nature Communications on February 23, 2024. Data on the microbiota of the patients in the MIND-DC trial were published simultaneously in the same journal.
Read the full clinical paper here: Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial | Nature Communications
Read the full microbiota paper here:Influence of microbiota-associated metabolic reprogramming on clinical outcome in patients with melanoma from the randomized adjuvant dendritic cell-based MIND-DC trial | Nature Communications
Bol KF, Schreibelt G, Bloemendal M, van Willigen WW, Hins-de Bree S, de Goede AL, et al. Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial. Nat Commun. 2024;15(1):1632.
