Anti-tumor and immune modulating activity of T cell induced tumor-targeting effectors (TITE)
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ORIGINAL ARTICLE
Anti‑tumor and immune modulating activity of T cell induced tumor‑targeting effectors (TITE) Archana Thakur1 · Sri Vidya Kondadasula2 · Kyungmin Ji3 · Dana L. Schalk1 · Edwin Bliemeister1 · Johnson Ung1 · Amro Aboukameel2 · Eli Casarez1 · Bonnie F. Sloane3 · Lawrence G. Lum1 Received: 27 April 2020 / Accepted: 4 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Adoptive transfer of Bispecific antibody Armed activated T cells (BATs) showed promising anti-tumor activity in clinical trials in solid tumors. The cytotoxic activity of BATs occurs upon engagement with tumor cells via the bispecific antibody (BiAb) bridge, which stimulates BATs to release cytotoxic molecules, cytokines, chemokines, and other signaling molecules extracellularly. We hypothesized that the release of BATs Induced Tumor-Targeting Effectors (TITE) by this complex interaction of T cells, bispecific antibody, and tumor cells may serve as a potent anti-tumor and immune-activating immunotherapeutic approach. In a 3D tumorsphere model, TITE showed potent cytotoxic activity against multiple breast cancer cell lines compared to control conditioned media (CM): Tumor-CM (T-CM), BATs-CM (B-CM), BiAb Armed PBMC-CM (BAP-CM) or PBMC-CM (P-CM). Multiplex cytokine analysis showed high levels of T h1 cytokines and chemokines; phospho-protein signaling array data suggest that the prominent JAK1/STAT1 pathway may be responsible for the induction and release of Th1 cytokines/chemokines in TITE. In xenograft breast cancer models, IV injections of 10× concentrated TITE (3×/week for 3 weeks; 150 μl TITE/injection) was able to inhibit tumor growth significantly (ICR/scid, p
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