Abstract A140: A T-cell utilizing bispecific anti-CD3/GD2 construct mediates superior in vitro efficacy compared to CH14.18 mAb in neuroblastoma patients after allogeneic SCT

• Published in: Cancer immunology research 2019-02, Vol.7 (2_Supplement), p.A140-A140
• Main Authors: Lang, Anne-Marie, Jung, Gundram, Seidel, Ursula, Heubach, Florian, Rabsteyn, Armin, Schlegel, Patrick, Seitz, Christian, Ribeiro, Emmanuelle Moraes, Handgretinger, Rupert, Lang, Peter
• Format: Article
• Language: English
• ISSN: 2326-6066; 2326-6074
• DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A140

Introduction: Whereas immunotherapy in high-risk/relapsed neuroblastoma with standard antibody formats targeting the tumor associated antigen GD2 is currently used after autologous/allogeneic stem cell transplantation (SCT), T-cells have rarely been addressed as effectors. Bispecific antibodies can bring T-cells into close proximity to tumor cells and activate them through the CD3 region, which ultimately leads to targeT-cell elimination. They lack the Fc-domain and cannot trigger ADCC or CDC as NK-cells. An example for bispecific antibodies is NG-CU (developed at the Department of Immunology, University of Tuebingen), which recognizes CD3 and GD2 as target antigens. The tumor antigen specific antibody domain, derived from a fab fragment of GD2 14.18 antibody and the T-cell recruiting antibody domain, derived from single chain variable fragment (scFv fragment) of UCHT-1 (CD3) are linked by modified CH2 domain. We investigated whether the bispecific antibody NG-CU might be an alternative to the therapeutic monoclonal antibody CH14.18, which mediates CDC and ADCC through NK-cells. Method: Different antibody concentrations and effector to target ratios (E:T) were evaluated using the xCELLigence RTCA system, PBMCs (healthy donors and patients after allogeneic SCT) and the neuroblastoma cell lines LS and LAN-1. CDC was evaluated using autologous serum.Results: NG-CU showed enhanced cytotoxicity compared to CH14.18. Median specific lysis (n=3) after 12/24/48 hrs (effectors: healthy PBMCs, E:T=5:1) with LS cells was: 55/73/77% (CH14.18, 1 µg/ml) vs. 70/100/100% (NG CU, 100ng/ml). P values with Mann-Whitney test: p=0,0244; p