1. Humanization of a strategic CD3 epitope enables evaluation of clinical T-cell engagers in a fully immunocompetent in vivo model
Julie, A. Z., et al. Sci Rep. 2022 Mar. doi: 10.1038/s41598-022-06953-7
“T-cell engagers (TCEs) are a growing class of biotherapeutics being investigated in the clinic for treatment of a variety of hematological and solid tumor indications. However, preclinical evaluation of TCEs in vivo has been mostly limited to xenograft tumor models in human T-cell reconstituted immunodeficient mice, which have a number of limitations. To explore the efficacy of human TCEs in fully immunocompetent hosts, we developed a knock-in mouse model (hCD3E-epi) in which a 5-residue N-terminal fragment of murine CD3-epsilon was replaced with an 11-residue stretch from the human sequence that encodes for a common epitope recognized by anti-human CD3E antibodies in the clinic.”

2. Comparison of CD3e Antibody and CD3e-sZAP Immunotoxin Treatment in Mice Identifies sZAP as the Main Driver of Vascular Leakage
Shihyoung, K., et al. Toxins (Basel). 2022 Jun. doi: 10.3390/toxins14060410
“Anti-CD3-epsilon (CD3e) monoclonal antibodies (mAbs) and CD3e immunotoxins (ITs) are promising targeted therapy options for various T-cell disorders. CD3e-ITs may induce vascular leak syndrome (VLS) via the CD3e binding portion of IT, that may induce an excessive activation of T cells, and the toxin portion that can directly damage vascular endothelial cells and induce extensive cell death and inflammation. To dissect and compare the roles of these two components of ITs in inducing VLS in mice, we created a new murine CD3e-IT by conjugating the sZAP with S-CD3e-mAb.”

3. TCRαβ/CD3 disruption enables CD3-specific antileukemic T cell immunotherapy
Rasmus, O. N., et al. JCI Insight. 2018 Jul. doi: 10.1172/jci.insight.99442
“T cells engineered to express chimeric antigen receptors (CARs) against B cell antigens are being investigated as cellular immunotherapies. Similar approaches designed to target T cell malignancies have been hampered by the critical issue of T-on-T cytotoxicity, whereby fratricide or self-destruction of healthy T cells prohibits cell product manufacture. T cells were transduced with a lentiviral vector incorporating an anti-CD3ε CAR derived from OKT3, either before or after TALEN-mediated disruption of the endogenous TCRαβ/CD3 complex.”

4. A humanized CD3ε-knock-in mouse model for pre-clinical testing of anti-human CD3 therapy
Paul, S. M., et al. PLoS One. 2021 Feb. doi: 10.1371/journal.pone.0245917
“Pre-clinical murine models are critical for translating drug candidates from the bench to the bedside. In this study, we report a murine genetic knock-in model which expresses both a murine and a humanized-CD3ε-exon, rendering it sensitive to manipulation with anti-human CD3. Our results show a viable humanized CD3 murine model that develops normally, is functionally engaged by anti-human CD3 and can instruct on pre-clinical tests of anti-human CD3 antibodies.”

5. Differential depletion of total T cells and regulatory T cells and prolonged allotransplant survival in CD3Ɛ humanized mice treated with polyclonal anti human thymocyte globulin
Maja, B., et al. PLoS One. 2017 Mar. doi: 10.1371/journal.pone.0173088
“Thymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent to prevent or treat allotransplant rejection. In the field of allotransplantation, another antibody-based immunosuppressive therapy specifically targets CD3 molecules, where the main effect of anti-CD3 monoclonal antibodies (mAbs) (OKT3) is T cell depletion. We found that a single intravenous (i.v.) injection of ATG into BALB/c huCD3Ɛ transgenic mice resulted in T cell depletion in the circulation and in the secondary lymphoid organs, with concomitant preservation of Tregs.”