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Immunology

Abstract 3500: T cells redirected against HER2 for the adoptive immunotherapy for HER2-positive osteosarcoma

Nabil Ahmed, Vita Brawley, Oumar Diouf, Peter Anderson, John Hicks, Lisa Wang, Gianpietro Dotti, Winfried Wels, Hao Liu, Adrian Gee, Cliona Rooney, Malcolm Brenner, Helen Heslop and Stephen Gottschalk
Nabil Ahmed
1Baylor College of Medicine, Houston, TX
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Vita Brawley
1Baylor College of Medicine, Houston, TX
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Oumar Diouf
1Baylor College of Medicine, Houston, TX
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Peter Anderson
2MD Anderson Cancer Center, Houston, TX
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John Hicks
1Baylor College of Medicine, Houston, TX
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Lisa Wang
1Baylor College of Medicine, Houston, TX
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Gianpietro Dotti
1Baylor College of Medicine, Houston, TX
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Winfried Wels
3Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus, Frankfurt, Germany
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Hao Liu
1Baylor College of Medicine, Houston, TX
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Adrian Gee
1Baylor College of Medicine, Houston, TX
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Cliona Rooney
1Baylor College of Medicine, Houston, TX
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Malcolm Brenner
1Baylor College of Medicine, Houston, TX
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Helen Heslop
1Baylor College of Medicine, Houston, TX
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Stephen Gottschalk
1Baylor College of Medicine, Houston, TX
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DOI: 10.1158/1538-7445.AM2012-3500 Published April 2012
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Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL

Abstract

INTRODUCTION: The prognosis for patients with advanced osteosarcoma (OS) has not improved over the last two decades. Hence novel biologically-based therapies, such as immunotherapy, are needed for these patients. We have shown in preclinical studies that T cells, genetically modified with a HER2-specific chimeric antigen receptor (CAR; HER2-CAR T cells), kill HER2+ OS cells ex vivo and induce regression of HER2+ OS xenografts in animal models. Based on these findings we developed a Phase I/II clinical study with HER2-CAR T cells in patients with metastatic and/or recurrent OS. METHODS: The primary objective of this clinical trial is to determine the safety of escalating doses of HER2-CAR T cells in patients with advanced HER2+ OS. The secondary objective is to determine the expansion, persistence and anti-tumor effects of infused HER2-CAR T cells. RESULTS: 43 (78%) out of 55 screened OS patients had HER2+ tumors. Twenty one HER2-CAR T-cell lines have been generated to date by retroviral transduction. Median HER2-CAR expression was 67.4% (range 50.7-85.6%) and HER2-CAR T cells killed HER2+ OS cells in contrast to non-transduced T cells (p <0.0001). The median CD4+:CD8+ T-cell ratio was 1:1.3, and T-cell products contained naïve (CD45RA+; median: 11.8%; range 2.4-33.2%), effector memory (CD45RO+/CCR7-/CD62L-; median: 29.3%; range: 7.8-67.5%), and central memory T cells (CD45RO+/CD62L+; median 55.9%; range: 21.9-87.9%). Nine patients have been infused so far at HER2-CAR T-cell doses between 104/m2 to 1x106/m2. Infusions were well tolerated without systemic side effects, and no increase of proinflammatory cytokines (IL-2, IFN-γ, GM-CSF, TNF-α) was observed in the patients’ plasma post infusion. HER2-CAR T cells were detectable for up to 3 months post infusion. CONCLUSION: HER2-CAR T cells have shown promising antitumor activity in preclinical OS animal models. We are currently evaluating the safety and efficacy of HER2-CAR T cells in a Phase I/II clinical study. Initial safety data at low T-cell dose levels are encouraging, warranting further active exploration of HER2-CAR T-cell based therapies for OS and other HER2+ malignancies.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3500. doi:1538-7445.AM2012-3500

  • ©2012 American Association for Cancer Research
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Cancer Research: 72 (8 Supplement)
April 2012
Volume 72, Issue 8 Supplement
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Abstract 3500: T cells redirected against HER2 for the adoptive immunotherapy for HER2-positive osteosarcoma
Nabil Ahmed, Vita Brawley, Oumar Diouf, Peter Anderson, John Hicks, Lisa Wang, Gianpietro Dotti, Winfried Wels, Hao Liu, Adrian Gee, Cliona Rooney, Malcolm Brenner, Helen Heslop and Stephen Gottschalk
Cancer Res April 15 2012 (72) (8 Supplement) 3500; DOI: 10.1158/1538-7445.AM2012-3500

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Abstract 3500: T cells redirected against HER2 for the adoptive immunotherapy for HER2-positive osteosarcoma
Nabil Ahmed, Vita Brawley, Oumar Diouf, Peter Anderson, John Hicks, Lisa Wang, Gianpietro Dotti, Winfried Wels, Hao Liu, Adrian Gee, Cliona Rooney, Malcolm Brenner, Helen Heslop and Stephen Gottschalk
Cancer Res April 15 2012 (72) (8 Supplement) 3500; DOI: 10.1158/1538-7445.AM2012-3500
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Cancer Research Online ISSN: 1538-7445
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