Precision BioSciences Inc (DTIL)

[MI Dendream]

Oral administration of anti-CD3 monoclonal antibody as a potent immunomodulatory agent: preclinical and clinical studies

Whereas intravenous administration of anti-CD3 acts via transient depletion of the activated effector T cells, oral anti-CD3 mAbs act by the induction of Tregs, thus causing the immunomodulation of the CD3/TCR complex and decreasing common unwanted adverse effects associated with parenteral administration, such as CRS 61. Oral anti-CD3 mAb, unlike its intravenous counterparts, affects the gut immune system and mesenteric lymph nodes (MLNs), thus promoting Treg activity without inducing generalized immunosuppression 62. This mode of therapy uses the gut immune system and underlying lamina propria for the generation of immune signals, thereby inducing a favourable systemic immune response 23, 24.

The induction of regulatory cells has been described following oral administration of anti-CD3 mAb in mice and in humanized mice, following migration of the antibodies to the gut wall 63. The oral administration of anti-CD3 mAb in experimental autoimmune encephalitis, a model of multiple sclerosis, induces CD4+CD25– latency-associated peptide (LAP)+ T cells that exhibit regulatory properties 64, 65. Similarly, oral anti-CD3 mAb suppresses low-dose streptozotocin-induced and non-obese diabetic (NOD) diabetes models of T1D through the induction of IL-10-secreting CD4+CD25–LAP+ regulatory cells, thus decreasing T cell proliferation and IFN-? and IL-17 production and increasing TGF-ß production 66-68. Oral anti-CD3 is beneficial in animal models of colitis 69 and atherosclerosis 70.

Orally and intranasally administered anti-CD3 have been found to suppress autoantibody production in a mouse lupus model 71, 72. An increased release of IL-10 in the serum has been demonstrated and suggested to account for the protective effects of systemically administered anti-CD3 mAbs 59, 73.

https://onlinelibrary.wiley.com/doi/10.1111/cei.13159