Immunotherapy in atypical teratoid-rhabdoid tumors: Data from a survey of the HGG-Immuno Group

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• 作者：Stefaan W. van Gool¹ ; Stefan Holm² ; Johannes Rachor³ ; Lars Adamson⁵ ; Antje Technau³ ; Eberhard Maass⁶ ; Michael C. Frü ; hwald⁷ ; Paul G. Schlegel³ ; ⁴ ; Matthias Eyrich³ ; ^{eyrich_m@ukw.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：atypical teratoid-rhabdoid tumor ; dendritic cells ; immunotherapy ; pediatric CNS tumors ; therapeutic vaccination
• 刊名：Cytotherapy
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：18
• 期：9
• 页码：1178-1186
• 全文大小：478 K

文摘

Atypical rhabdoid/teratoid tumors (AT/RT) are the most common brain tumors in infants and associated with a dismal prognosis. Although intensification of first-line therapy has resulted in improvement of overall survival, novel treatment strategies are needed. Because immunotherapy has resulted in remarkable results in several adult tumor entities, incorporation of immunotherapy into AT/RT treatment offers a novel alternative.

Methods

We retrospectively analyzed data from 7 AT/RT patients from five countries treated within the HGG-Immuno Consortium. Two patients were ≤1 year and 4 patients were ≤2 years of age at diagnosis. All received immunotherapy with autologous, tumor-lysate-loaded dendritic cells (DCs) on a compassionate use basis using a schedule of three to four weekly DC vaccinations with up to 2 × 10⁷ DCs per vaccine, followed by three lysate boosts each 1 month apart.

Results

Monocyte collections (median age at apheresis 31.5, range 20–143 months) and vaccinations were uneventful without any severe adverse event related to the vaccine, demonstrating feasibility and safety in this very young age group. Two children received immunotherapy during their primary and the remaining five during second- or third-line therapy. Three of seven patients survived long term with a follow-up of 143, 138 and 46 months, with at least two of them harboring somatic mutations. One long-term survivor was vaccinated during primary treatment and the other two after first or second relapse/progression. Two analyzed patients showed positive CD8⁺ T-cell responses after vaccination.

Discussion

Our data demonstrate that anti-tumor immunotherapy with autologous DCs is feasible and safe in young children with ATRTs and that this approach warrants further investigation in controlled clinical trials.