Antitumor activity of CD56-chimeric antigen receptor T cells in neuroblastoma and SCLC models.

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Antitumor activity of CD56-chimeric antigen receptor T cells in neuroblastoma and SCLC models.

Oncogene. 2018 Apr 06;:

Authors: Crossland DL, Denning WL, Ang S, Olivares S, Mi T, Switzer K, Singh H, Huls H, Gold KS, Glisson BS, Cooper LJ, Heymach JV

Abstract
The CD56 antigen (NCAM-1) is highly expressed on several malignancies with neuronal or neuroendocrine differentiation, including small-cell lung cancer and neuroblastoma, tumor types for which new therapeutic options are needed. We hypothesized that CD56-specific chimeric antigen receptor (CAR) T cells could target and eliminate CD56-positive malignancies. Sleeping Beauty transposon-generated CD56R-CAR T cells exhibited αβT-cell receptors, released antitumor cytokines upon co-culture with CD56+ tumor targets, demonstrated a lack of fratricide, and expression of cytolytic function in the presence of CD56+ stimulation. The CD56R-CAR+ T cells are capable of killing CD56+ neuroblastoma, glioma, and SCLC tumor cells in in vitro co-cultures and when tested against CD56+ human xenograft neuroblastoma models and SCLC models, CD56R-CAR+ T cells were able to inhibit tumor growth in vivo. These results indicate that CD56-CARs merit further investigation as a potential treatment for CD56+ malignancies.

PMID: 29622795 [PubMed - as supplied by publisher]

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