Targeted Cancer Immunotherapy by Nanoparticle T Cell Engagers

• DOI: 10.1096/fasebj.2022.36.s1.r2489
• Publication Date: 2022-05-03T08:34:55Z
• Authors: Berit Lubben; Kinan Alhallak; Jennifer Sun; Barbara Muz; Hannah Bash; Chaelee Park; Ola Adebayo; Samuel Achilefu; John F. DiPersio; Abdel K. Azab
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Acute myeloid leukemia (AML) is the most common type of leukemia. Emerging immunotherapies such as chimeric antigen receptor T (CAR-T) cells and cell engagers (TCEs), have potential to enhance recognition response against cancers, but come with serious limitations short half-life, complex production, high cost, inability customize for another antigen. To overcome these limitations, we previously developed a nanoparticle-based (nanoTCEs) technology that has longer half-life (60h vs 2h TCEs), convenient make, easily customizable, robustly activates cancer killing. In this study, hypothesized nanoTCEs targeting CD33/CD3 would effectively activate in an AML disease model.Liposomes were produced via thin-film hydration method cholesterol, DPPC, DSPE-PEG200 at molar ratio 30:65:5 respectively (Figure 1A). created by conjugating anti-CD3 anti-CD33 monoclonal antibodies (mAbs) on liposome surface streptavidin-biotin chemistry. Liposome binding human lines was performed fluorescently labeled 2 hours. The activation subsets killing analyzed flow cytometry after 4 days 3D culture model. For vivo efficacy, immunodeficient NCG mice inoculated line received Isotype/CD3 or injections (0.5 mg/mouse) weekly monitored tumor progression survival.AML (K052, MOLM-14. NOMO-1, THP-1) exhibited expression CD33 compared controls. bound higher specificity than isotype addition, induced increased both CD4+ CD8+ 1B, 1C) achieved greater untreated groups 1D). Lastly, our results showed nanoTCE extended survival decreased bearing treated mice. By day 66 none cohort alive, while 100% remained living 2).This study shows are promising novel platform immunotherapy AML. demonstrated specific engagement cells, which vitro vivo. It not only circumvented traditional engagers, also presented numerous advantages production time, low superior pharmacokinetic profile. Moreover, highly customizable can be tailored target multiple antigens simultaneously. current findings provide strong preclinical basis future first-in-human clinical trials immunotherapy.