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2012 Reseach Abstract

Enhanced Cytotoxicity toward CD20-Expressing Non Hodgkins Lymphoma (NHL) Cells by Ex-Vivo Expanded Activated T Cells (ATCs) Armed with Anti- CD3/Anti-CD20 Bispecific Antibodies

Investigator: Najibah Rehman
Mentor: Abhinav Deol, MD

Background: Non Hodgkins Lymphoma (NHL) involves clonal expansion of B cells due to proto-oncogene or tumor suppressor gene dysregulation, originating from B cells in 85% of cases. The 5-year survival for NHL is 63% and while patients are classified into low, intermediate, and poor risk groups, the highest risk of relapse are in those who fall into the poor risk category.
Treatment of NHL varies depending on many individual factors that will determine response to treatment modalities such as combination chemotherapy, chemo- radiation, monoclonal antibody therapy (anti-CD20), and bone marrow transplant. However, despite aggressive therapies like stem cell transplant, patients with high-risk disease can relapse such that novel therapeutic strategies are necessary. Therefore, this study was directed toward development of an immunotherapeutic agent specific for NHL cells using Activated T Cells (ATCs) armed with bispecific antibodies.

Hypothesis: ATCs expanded with OKT3 and IL-2 harvested at varying time points in cell culture (Days 8,10,12,14) armed with Anti-CD3/Anti-CD20 bispecific antibodies (BiAb) will exhibit enhanced cytotoxicity toward CD20 positive NHL cell lines compared to unarmed ATCs.

Results: Increased bispecific antibody killing was observed at days 8 vs. 12 vs. 14 in culture (17.2% vs. 22.7% vs. 31.2%) and in a stepwise pattern comparing ATCs vs. OKT3 stimulation vs. BiAb stimulation (day 8: 4.9% vs. 9.8% vs. 17.2%, day 12: 6.8% vs. 20.2% vs. 22.7%, day 14: 6.8% vs. 15.1% vs. 31.2%). In our quality control assays using ATCs against Daudi cells, the determined cutoff for Anti- CD20 killing was set at 25% so it is evident that killing was optimal using day 14 ATCs + Anti-CD3/Anti-CD20 BiAb with 31.2% cytotoxicity, versus 22.7% killing with ATCs + BiAb at day 12 which remained very close to the cutoff.

Conclusion: Cytotoxicity was considerably higher in our experimental results using ATCs armed with Anti-CD3/Anti-CD20 antibodies compared to cytotoxicity against ATCs alone. We therefore confirmed, in this data set, that day 14 is the optimal time point at which the maximal cytotoxicity is demonstrated. These results are encouraging that ATCs armed with Anti-CD3/Anti-CD20 bispecific antibodies demonstrate increased killing compared to controls, and that optimal cytotoxicity in our experiments was obtained at day 14 of culture.

Last Updated: 12/6/13

Updated on December 6, 2013.

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