Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with α-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma

Hideho Okada, Pawel Kalinski, Ryo Ueda, Aki Hoji, Gary Kohanbash, Teresa E. Donegan, Arlan H. Mintz, Johnathan A. Engh, David L. Bartlett, Charles K. Brown, Herbert Zeh, Matthew P. Holtzman, Todd A. Reinhart, Theresa L. Whiteside, Lisa H. Butterfield, Ronald L. Hamilton, Douglas M. Potter, Ian F. Pollack, Andres M. Salazar, Frank S. Lieberman

研究成果: Article査読

399 被引用数 (Scopus)

抄録

Purpose: A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel vaccination with α-type 1 polarized dendritic cells (αDC1) loaded with synthetic peptides for glioma-associated antigen (GAA) epitopes and administration of polyinosinic-polycytidylic acid [poly(I:C)] stabilized by lysine and carboxymethylcellulose (poly-ICLC) in HLA-A2 + patients with recurrent malignant gliomas. GAAs for these peptides are EphA2, interleukin (IL)-13 receptor-α2, YKL-40, and gp100. Patients and Methods: Twenty-two patients (13 with glioblastoma multiforme [GBM], five with anaplastic astrocytoma [AA], three with anaplastic oligodendroglioma [AO], and one with anaplastic oligoastrocytoma [AOA]) received at least one vaccination, and 19 patients received at least four vaccinations at two αDC1 dose levels (1 × or 3 × 107/dose) at 2-week intervals intranodally. Patients also received twice weekly intramuscular injections of 20 μg/kg poly-ICLC. Patients who demonstrated positive radiologic response or stable disease without major adverse events were allowed to receive booster vaccines. T-lymphocyte responses against GAA epitopes were assessed by enzyme-linked immunosorbent spot and HLA-tetramer assays. Results: The regimen was well-tolerated. The first four vaccines induced positive immune responses against at least one of the vaccination-targeted GAAs in peripheral blood mononuclear cells in 58% of patients. Peripheral blood samples demonstrated significant upregulation of type 1 cytokines and chemokines, including interferon-α and CXCL10. Nine (four GBM, two AA, two AO, and one AOA) achieved progression-free status lasting at least 12 months. One patient with recurrent GBM demonstrated sustained complete response. IL-12 production levels by αDC1 positively correlated with time to progression. Conclusion: These data support safety, immunogenicity, and preliminary clinical activity of poly-ICLC-boosted αDC1-based vaccines.

本文言語English
ページ(範囲)330-336
ページ数7
ジャーナルJournal of Clinical Oncology
29
3
DOI
出版ステータスPublished - 2011 1 20
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

フィンガープリント

「Induction of CD8<sup>+</sup> T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with α-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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