Although many clinical trials have explored the adoptive transfer of ex vivo expanded autologous regulatory T cells (Tregs), pharmacodynamic read-outs and proof of clinical efficacy have been difficult to obtain. We will describe the rationale, preclinical evidence, and emerging clinical trial data on the use of chimeric antigen receptor (CAR) Tregs to induce allograft tolerance in liver transplantation

The complex microenvironments of solid tumours present multiple barriers to therapeutic efficacy with current treatments, including CAR T cells. To overcome these hurdles, we have designed and developed a novel 'adaptor' CAR, which demonstrates greater potency, proliferation, and durability of response compared to traditional 'linear' CARs. This talk will detail the development of this novel CAR structure from initial design to the commencement of an ongoing first-in-human Phase I clinical trial.

The cost effectiveness of CAR T is a current limitation. A number of approaches are being explored to address this, but are any of these the solution?

While chimeric antigen receptor (CAR) T cell therapy has revolutionized hematology, its efficacy in solid malignancies still remains behind its possibilities. Host derived factors, which determine the physical and immunological barriers of the tumor microenvironment, are key targets that need to be analyzed to remove or modulate them favorably. We apply an advanced target identification and genetic engineering platform to tailor CAR T cells to the hostile milieu and overcome the limitations of cellular therapy.

The adoptive transfer of regulatory T cells (Tregs), a subset of T cells armed with more than a dozen suppression mechanisms, but that do not proliferate and lack cytotoxic function, could represent a safe alternative for restoring tolerance in T1D and celiac disease patients. Herein we redirected the specificity of Tregs by orthotropic replacement of their TCRs. Gluten-reactive or islet-specific Tregs showed tissue specific homing. 

Recent clinical trials in glioblastoma have shown that CAR T cell therapy is safe and can induce strong anti-tumour activity, but this effect is only transient. Here, we will discuss the use of mRNA CAR T cells for glioblastoma and how to overcome the current challenges of tumour-antigen heterogeneity and specificity as well as CAR T cell trafficking, persistence, and resistance to an immunosuppressive tumour environment.

The presentation will show a unique pipeline for generating macrophages from human induced pluripotent stem cells (iPSCs), enabling the production of genetically-engineered macrophages for a wide range of therapeutic applications. This system involves differentiating iPSCs into macrophages with precise control over their development and genetic modifications. The engineered macrophages have enhanced targeting and immune-modulatory properties, offering great potential for advancing cancer immunotherapies, particularly for solid tumours. Additionally, this approach can be applied to treat autoimmune disorders, chronic inflammation, and aid in tissue repair, providing a versatile platform for macrophage-based therapies across multiple disease areas.