Abstract LB-083: Phase I study of T cells redirected to EGFRvIII with a chimeric antigen receptor in patients with EGFRvIII+ glioblastoma

Media type: E-Article

Title: Abstract LB-083: Phase I study of T cells redirected to EGFRvIII with a chimeric antigen receptor in patients with EGFRvIII+ glioblastoma

Contributor: O’Rourke, Donald M.; Nasrallah, MacLean P.; Morrissette, Jennifer; Melenhorst, Jan J.; Lacey, Simon F.; Mansfield, Keith; Martinez-Lage, Maria; Desai, Arati; Brem, Steven; Maloney, Eileen; Mohan, Suyash; Wang, Sumei; Verma, Gaurav; Navenot, Jean-Marc; Shen, Angela; Zheng, Zhaohui; Levine, Bruce L.; Okada, Hideho; June, Carl H.; Maus, Marcela V.

imprint: American Association for Cancer Research (AACR), 2016

Language: English

DOI: 10.1158/1538-7445.am2016-lb-083

ISSN: 0008-5472; 1538-7445

Keywords: Cancer Research ; Oncology

Origination:

Footnote:

Description: Abstract We initiated a Phase I study of intravenous delivery of autologous T cells re-directed to the EGFR variant III mutation by means of a lentiviral vector encoding a chimeric antigen receptor (CAR). Patients with recurrent glioblastoma (GBM) have their tumors screened for the presence of the EGFRvIII mutation by a next-generation sequencing based assay. Eligible patients undergo leukapheresis for collection of autologous T cells, which are genetically modified ex vivo to express the EGFRvIII CAR, expanded, and then cryopreserved for infusion. We report results on the nine patients we have treated. We targeted a challenging subset of GBM patients, with multi-focal residual, progressive disease refractory to standard and experimental therapies, including temozolomide, bevacizumab, and radiation. To date, we have found that infusion of 1-5×10⁁8 CART-EGFRvIII cells is feasible to manufacture and infusion is safe, without evidence of off-tumor toxicity or cross-reactivity to wild type EGFR. No clinical or laboratory signs of systemic cytokine release syndrome have been observed, though elevations in serum IL-6 occur concurrently with CART-EGFRvIII expansion in the peripheral blood. One patient developed non-convulsive status epilepticus nine days after CART-EGFRvIII infusion, which resolved with standard treatment and anti-cytokine therapy. All patients have had significant expansion of CART-EGFRvIII cells between 7-10 days post-infusion, as measured by flow cytometry and quantitative PCR in peripheral blood samples. Five patients have undergone surgical resection of tumor between 6-120 days after infusion, and pathologic evaluation has demonstrated infiltration of activated CAR T cells, recruitment of new T cells (as assessed by next generation T cell receptor deep sequencing), and specific EGFRvIII target antigen loss in GBM cells in some cases. These findings provide evidence that CART-EGFRvIII cells are safe, without evidence of off-target toxicity or cytokine release syndrome, and are immunologically active. The data also suggest a mechanism of antigen editing by activated CART-EGFRvIII cells that track to specific EGFRvIII GBM cells. Citation Format: Donald M. O’Rourke, MacLean P. Nasrallah, Jennifer Morrissette, Jan J. Melenhorst, Simon F. Lacey, Keith Mansfield, Maria Martinez-Lage, Arati Desai, Steven Brem, Eileen Maloney, Suyash Mohan, Sumei Wang, Gaurav Verma, Jean-Marc Navenot, Angela Shen, Zhaohui Zheng, Bruce L. Levine, Hideho Okada, Carl H. June, Marcela V. Maus. Phase I study of T cells redirected to EGFRvIII with a chimeric antigen receptor in patients with EGFRvIII+ glioblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-083.

Access State: Open Access

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