Objective
This proposal aims to test the utility of TZT-N78 as a therapeutic agent to block the autoimmune attack on beta cells, through T1D mouse model studies.
Background Rationale
Type 1 diabetes (T1D) is a chronic autoimmune disorder characterized by the immune-mediated destruction of insulin-producing beta cells in the pancreas, leading to a deficiency of insulin and dysregulated glucose metabolism. This results in long-term complications such as cardiovascular disease, nephropathy, neuropathy, and retinopathy. The global incidence of T1D is rapidly increasing, especially in children and young adults, emphasizing the urgent need for improved therapeutic interventions. In the United States alone, over 2 million people are affected by T1D. Despite advances in insulin delivery and glucose monitoring technologies, individuals with T1D continue to face significant risks of life-threatening complications. Therefore, research into the underlying immunopathology and novel treatment strategies is critical to improving patient outcomes.
In T1D, the adaptive immune system, particularly T cells, mistakenly attacks the insulin-producing beta cells in the pancreas. This immune response is initiated by various stressors that trigger the activation and infiltration of T cells, which recognize and destroy beta cells. Innate immunity plays a crucial role in amplifying the immune response, with dendritic cells (DCs) and macrophages acting as mediators between beta cells and T cells. Current treatments primarily rely on exogenous insulin administration, which fails to address the underlying autoimmune destruction of beta cells. While advances in immunomodulatory therapies, such as anti-CD3 monoclonal antibodies and regulatory T cell-based approaches, show promise in delaying disease onset, they are limited by incomplete efficacy, off-target effects, and the risk of immunosuppression. Additionally, islet transplantation offers a potential cure but is constrained by donor shortages, immune rejection, and the need for lifelong immunosuppressive drugs. Given these limitations, there is a pressing need for novel therapies that target immune dysregulation while preserving beta cell function and minimizing systemic immune suppression. Targeting innate immune cells, such as monocytes, macrophages, and DCs, through receptors like TLR7, offers a promising strategy to prevent T1D onset and disease progression.
Description of Project
Tezcat Biosciences is an early-stage biotechnology company focused on developing innovative therapeutics to treat recalcitrant diseases. In this proposal, Tezcat is exploring the utility of a novel protein-drug conjugate carrying an anti-inflammatory agent to innate immune cells for the treatment of Type 1 Diabetes.
Anticipated Outcome
We anticipate that treatment with TZT-N78 will significantly delay the onset of T1D compared to the control arm. We also anticipate that this will be accompanied by a reduced disease burden and favorable immune profile in comparison to control and T-cell based therapies.
Relevance to T1D
If successful, TZT-N78 will represent a novel therapeutic approach to combat the onset and progression of T1D that warrants further development towards the clinic.