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Il13 CAR

Sujita Sukumaran, Norihiro Watanabe, Pradip Bajgain, Kanchana Raja, Somala Mohammed, William E Fisher, Malcolm K Brenner, Ann M Leen, Juan F Vera
The adoptive transfer of chimeric antigen receptor (CAR)-modified T cells has produced tumor responses even in patients with refractory diseases. However, the paucity of antigens that are tumor selective has resulted, on occasion, in "on-target, off-tumor" toxicities. To address this issue, we developed an approach to render T cells responsive to an expression pattern present exclusively at the tumor by using a trio of novel chimeric receptors. Using pancreatic cancer as a model, we demonstrate how T cells engineered with receptors that recognize PSCA, TGFβ, and IL4, and whose endodomains recapitulate physiologic T cell signaling by providing signals for activation, co-stimulation and cytokine support, produce potent anti-tumor effects selectively at the tumor site...
June 7, 2018: Cancer Discovery
Christine E Brown, Behnam Badie, Michael E Barish, Lihong Weng, Julie R Ostberg, Wen-Chung Chang, Araceli Naranjo, Renate Starr, Jamie Wagner, Christine Wright, Yubo Zhai, James R Bading, Julie A Ressler, Jana Portnow, Massimo D'Apuzzo, Stephen J Forman, Michael C Jensen
PURPOSE: A first-in-human pilot safety and feasibility trial evaluating chimeric antigen receptor (CAR)-engineered, autologous primary human CD8(+) cytotoxic T lymphocytes (CTL) targeting IL13Rα2 for the treatment of recurrent glioblastoma (GBM). EXPERIMENTAL DESIGN: Three patients with recurrent GBM were treated with IL13(E13Y)-zetakine CD8(+) CTL targeting IL13Rα2. Patients received up to 12 local infusions at a maximum dose of 10(8) CAR-engineered T cells via a catheter/reservoir system...
September 15, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Simone Krebs, Kevin K H Chow, Zhongzhen Yi, Tania Rodriguez-Cruz, Meenakshi Hegde, Claudia Gerken, Nabil Ahmed, Stephen Gottschalk
BACKGROUND AIMS: Outcomes for patients with glioblastoma remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL) 13Rα2, human epidermal growth factor receptor 2, epidermal growth factor variant III or erythropoietin-producing hepatocellular carcinoma A2 has shown promise for the treatment of glioma in preclinical models. On the basis of IL13Rα2 immunotoxins that contain IL13 molecules with one or two amino acid substitutions (IL13 muteins) to confer specificity to IL13Rα2, investigators have constructed CARS with IL13 muteins as antigen-binding domains...
August 2014: Cytotherapy
Seogkyoung Kong, Sadhak Sengupta, Betty Tyler, Anthony J Bais, Qiangzhong Ma, Saryn Doucette, Jinyuan Zhou, Ayguen Sahin, Bob S Carter, Henry Brem, Richard P Junghans, Prakash Sampath
PURPOSE: Glioblastoma multiforme (GBM) remains highly incurable, with frequent recurrences after standard therapies of maximal surgical resection, radiation, and chemotherapy. To address the need for new treatments, we have undertaken a chimeric antigen receptor (CAR) "designer T cell" (dTc) immunotherapeutic strategy by exploiting interleukin (IL)13 receptor α-2 (IL13Rα2) as a GBM-selective target. EXPERIMENTAL DESIGN: We tested a second-generation IL13 "zetakine" CAR composed of a mutated IL13 extracellular domain linked to intracellular signaling elements of the CD28 costimulatory molecule and CD3ζ...
November 1, 2012: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
L Chang, W C Chang, G McNamara, B Aguilar, J R Ostberg, M C Jensen
Background The role of co-stimulation in CD4+ T cell activation by professional APC is well established, while less is known of the role co-stimulation plays when CD4+ T cells interact directly with tumor cells. Methods Through genetic engineering of human CD4+ T cells, we tested the hypothesis that integration of co-stimulatory signaling domains within a tumor-targeting chimeric Ag receptor (CAR), the IL-13Ralpha2-specific IL-13-zetakine (IL13zeta), would enhance CD4+ T cell mediated responses against tumors that fail to express ligands for co-stimulatory receptors...
2007: Cytotherapy
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