Successful treatment of metastatic melanoma by adoptive transfer of blood-derived polyclonal tumor-specific CD4+ and CD8+ T cells in combination with low-dose interferon-alpha

A phase I/II study was conducted to test the feasibility and safety of the adoptive transfer of tumor-reactive T cells and daily injections of interferon-alpha (IFNα) in metastatic melanoma patients with progressive disease. Autologous melanoma cell lines were established to generate tumor-specific T cells by autologous mixed lymphocyte tumor cell cultures using peripheral blood lymphocytes. Ten patients were treated with on average 259 (range 38–474) million T cells per infusion to a maximum of six infusions, and clinical response was evaluated according to the response evaluation criteria in solid tumors (RECIST). Five patients showed clinical benefit from this treatment, including one complete regression, one partial response, and three patients with stable disease. No treatment-related serious adverse events were observed, except for the appearance of necrotic-like fingertips in one patient. An IFNα-related transient leucopenia was detected in 6 patients, including all responders. One responding patient displayed vitiligo. The infused T-cell batches consisted of tumor-reactive polyclonal CD8+ and/or CD4+ T cells. Clinical reactivity correlated with the functional properties of the infused tumor-specific T cells, including their in vitro expansion rate and the secretion of mainly Th1 cytokines as opposed to Th2 cytokines. Our study shows that relatively low doses of T cells and low-dose IFNα can lead to successful treatment of metastatic melanoma and reveals a number of parameters potentially associated with this success

Soligion : onderzoek naar religieus en levensbeschouwelijk geïnspireerde solidariteitsinitiatieven in de stad

Research into religiously inspired solidarity initiatives in the city While assumptions on secularisation have many of us believe that religion lost its relevance in the modern Western European context, daily practices in superdiverse cities show differently. Especially for people in societal vulnerable positions, religiously inspired solidarity initiatives sometimes prove to be more accessible and their solidarity more unconditional than solidarity initiatives provided by the welfare state. In the Soligion research project, we study religiously inspired solidarity initiatives in five Flemish cities and Brussels, and examine their position in the Belgian welfare regime. This article provides insight into our main motivations for conducting this research, the central research questions, the methods used in the project and the aspired output of the project. We aim to stimulate a complementary collaboration between religiously inspired solidarity initiatives, public organisations and (local) governments, both by researching their current interactions and by creating tools for public organisations and (local) governments to better understand and collaborate with religiously inspired solidarity initiatives

Belgische en Nederlandse stadsgeschiedenis in historische tijdschriften (2020)

Cities, Migration and Global Interdependenc

Phase I/II study protocol to assess safety and efficacy of adoptive cell therapy with anti-PD-1 plus low-dose pegylated-interferon-alpha in patients with metastatic melanoma refractory to standard of care treatments: the ACTME trial

Introduction Treatment with anti-PD-1 immunotherapy does not lead to long-lasting clinical responses in approximately 60% of patients with metastatic melanoma. These refractory patients, however, can still respond to treatment with tumour infiltrating lymphocytes (TIL) and interferon-alpha (IFNa). A combination of TIL, pegylated-interferon-alpha (PEG-IFNa) and anti-PD-1 is expected to provide a safe, feasible and effective therapy for patients with metastatic melanoma, who are refractory to standard of care treatment options.Methods and analysis Patients are treated in two phases. In phase I, the safety of the combination TIL and anti-PD-1 is assessed (cohort 1) according to CTCAE 4.03 criteria. Subsequently, the safety of cotreatment with PEG-IFNa is tested in cohort 2. The efficacy will be evaluated in the second phase of the trial. Efficacy is evaluated according to RECIST 1.1 and immune-related response criteria. Clinical and immunological parameters will be evaluated for their relation with clinical responsiveness.Ethics and dissemination Ethical approval of the trial was obtained from the Central Committee on Research Involving Human Subjects in the Netherlands. The trial results will be shared with the scientific community at (inter)national conferences and by publication in a peer-reviewed journal.Trial registration number NCT03638375; Pre-results