Abstract P40: Novel Monoclonal Antibody Kills Lymphoma Cells Via LFA-1/ICAM-1 Dependent, Antibody-Mediated Cellular Cytotoxicity
Rui Xue Lee, Patrick W. Jaynes, Edward K. Chow, Anand D. JeyasekharanAbstract
Background:
Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin’s lymphoma. DLBCL patients undergo a first line immunochemotherapy regimen, termed R-CHOP. Unfortunately, approximately 40% of treated patients eventually relapse, or are non-responsive. Thus, there is an urgent need to devise new treatment options. Recently, a novel monoclonal antibody (Antibody X) has been developed as a potential therapeutic strategy.
Methods:
CD16 (Fc receptor)-expressing NK92 cells were used as effector cells against target DLCBL cell lines in co-culture assays. A high-content, high-throughput drug screening tool was developed to test the effects of small molecule drugs in combination with immunotherapies.
Results:
We observed that instead of direct cytotoxicity or complement-dependent cytotoxicity, Antibody X exerted its anti-tumour effect primarily through antibody-dependent cellular cytotoxicity (ADCC). To understand the regulators of Antibody X-mediated killing, we utilised a newly developed high-content, high-throughput drug screening tool to evaluate the effects of over 1000 FDA approved compounds on Antibody X-mediated ADCC of DLBCL cells. We noted that dasatinib, ponatinib and bosutinib, had particularly inhibited the activity of Antibody X, but not imatinib and nilotinib. This may be attributed to the drugs’ inhibition of Src kinases. Dasatinib had also inhibited cellular contact between lymphoma cells and immune effector cells by blocking LFA-1/ICAM-1 immunological synapse formation. This ultimately led to a lack of release of cytolytic granules and absence of death in lymphoma cells.
Conclusion:
Overall, findings from this study revealed that Antibody X-mediated ADCC is dependent on Src activity and the successful formation of LFA-1/ICAM-1 immunological synapses. We also demonstrated that the novel high-content, high-throughput ADCC platform can be used for immunotherapy-based combinatorial drug screens and mechanistic evaluation of ADCC.
Citation Format:
Rui Xue Lee, Patrick W. Jaynes, Edward K. Chow, Anand D. Jeyasekharan. Novel Monoclonal Antibody Kills Lymphoma Cells Via LFA-1/ICAM-1 Dependent, Antibody-Mediated Cellular Cytotoxicity [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P40.