Results from a phase I clinical trial with IGN311, a fully humanized IgG1 antibody against Lewis Y in patients with solid tumors expressing Lewis Y antigen

Oruzio, Daniel; Aulmann, Christoph; Eller, Norbert; Mudde, Geert C.; Obwaller, O.; Waxenecker, Günter; Scheiber, Oliver; Stranner, Stefan; Schlimok, Günter

doi:10.1200/jco.2004.22.14_suppl.2624

Cited by 2 publications

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“…of marked differences in pharmacokinetics between patients. [44][45][46] Another potential complication arising from soluble serum antigen could be widespread triggering of large numbers of genetically redirected T cells, which could lead to toxicity because of massive cytokine release. However, the presence of Le Y -containing serum alone or soluble synthetic Le Y did not trigger secretion of the cytokine IFN-g (data not shown), suggesting that gene-modified T cells were nonresponsive to soluble antigen even at levels of 10 mg/mL.…”

Section: Discussionmentioning

confidence: 99%

The Lewis-Y Carbohydrate Antigen is Expressed by Many Human Tumors and Can Serve as a Target for Genetically Redirected T cells Despite the Presence of Soluble Antigen in Serum

Westwood¹,

Murray²,

Trivett³

et al. 2009

Journal of Immunotherapy

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In this study we aimed to determine the suitability of the Lewis-Y carbohydrate antigen as a target for immunotherapy using genetically redirected T cells. Using the 3S193 monoclonal antibody and immunohistochemistry, Lewis-Y was found to be expressed on a range of tumors including 42% squamous cell lung carcinoma, 80% lung adenocarcinoma, 25% ovarian carcinoma, and 25% colorectal adenocarcinoma. Expression levels varied from low to intense on between 1% and 90% of tumor cells. Lewis- was also found in soluble form in sera from both normal donors and cancer patients using a newly developed enzyme-linked immunosorbent assay. Serum levels in patients was often less than 1 ng/mL, similar to normal donors, but approximately 30% of patients had soluble Lewis-Y levels exceeding 1 ng/mL and up to 9 ng/mL. Lewis-Y-specific human T cells were generated by genetic modification with a chimeric receptor encoding a single-chain humanized antibody linked to the T-cell signaling molecules, T-cell receptor-zeta, and CD28. T cells responded against the Lewis-Y antigen by cytokine secretion and cytolysis in response to tumor cells. Importantly, the T-cell response was not inhibited by patient serum containing soluble Lewis-Y. This study demonstrates that Lewis-Y is expressed on a large number of tumors and Lewis-Y-specific T cells can retain antitumor function in the presence of patient serum, indicating that this antigen is a suitable target for this form of therapy.

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Section: Discussionmentioning

confidence: 99%