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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)330-336
Number of pages7
JournalJournal of Clinical Oncology
Volume29
Issue number3
DOIs
StatePublished - Jan 20 2011
Externally publishedYes

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Poly I-C
Carboxymethylcellulose Sodium
Glioma
Dendritic Cells
Lysine
Vaccination
T-Lymphocytes
Antigens
Peptides
Glioblastoma
Oligodendroglioma
Vaccines
Astrocytoma
Epitopes
Interleukin-13 Receptors
HLA-A2 Antigen
Safety
Immunosorbents
Intramuscular Injections
Interleukin-12

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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

In: Journal of Clinical Oncology, Vol. 29, No. 3, 20.01.2011, p. 330-336.

Research output: Contribution to journalArticle

Okada, H, Kalinski, P, Ueda, R, Hoji, A, Kohanbash, G, Donegan, TE, Mintz, AH, Engh, JA, Bartlett, DL, Brown, CK, Zeh, H, Holtzman, MP, Reinhart, TA, Whiteside, TL, Butterfield, LH, Hamilton, RL, Potter, DM, Pollack, IF, Salazar, AM & Lieberman, FS 2011, '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', Journal of Clinical Oncology, vol. 29, no. 3, pp. 330-336. https://doi.org/10.1200/JCO.2010.30.7744
Okada, Hideho ; Kalinski, Pawel ; Ueda, Ryo ; Hoji, Aki ; Kohanbash, Gary ; Donegan, Teresa E. ; Mintz, Arlan H. ; Engh, Johnathan A. ; Bartlett, David L. ; Brown, Charles K. ; Zeh, Herbert ; Holtzman, Matthew P. ; Reinhart, Todd A. ; Whiteside, Theresa L. ; Butterfield, Lisa H. ; Hamilton, Ronald L. ; Potter, Douglas M. ; Pollack, Ian F. ; Salazar, Andres M. ; Lieberman, Frank S. / 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. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 3. pp. 330-336.
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abstract = "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.",
author = "Hideho Okada and Pawel Kalinski and Ryo Ueda and Aki Hoji and Gary Kohanbash and Donegan, {Teresa E.} and Mintz, {Arlan H.} and Engh, {Johnathan A.} and Bartlett, {David L.} and Brown, {Charles K.} and Herbert Zeh and Holtzman, {Matthew P.} and Reinhart, {Todd A.} and Whiteside, {Theresa L.} and Butterfield, {Lisa H.} and Hamilton, {Ronald L.} and Potter, {Douglas M.} and Pollack, {Ian F.} and Salazar, {Andres M.} and Lieberman, {Frank S.}",
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T1 - 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

AU - Okada, Hideho

AU - Kalinski, Pawel

AU - Ueda, Ryo

AU - Hoji, Aki

AU - Kohanbash, Gary

AU - Donegan, Teresa E.

AU - Mintz, Arlan H.

AU - Engh, Johnathan A.

AU - Bartlett, David L.

AU - Brown, Charles K.

AU - Zeh, Herbert

AU - Holtzman, Matthew P.

AU - Reinhart, Todd A.

AU - Whiteside, Theresa L.

AU - Butterfield, Lisa H.

AU - Hamilton, Ronald L.

AU - Potter, Douglas M.

AU - Pollack, Ian F.

AU - Salazar, Andres M.

AU - Lieberman, Frank S.

PY - 2011/1/20

Y1 - 2011/1/20

N2 - 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.

AB - 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.

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