Immunotherapy has entered centre stage as a novel treatment modality for cancer. Immune checkpoint inhibitors and engineered T cells have delivered unprecedented clinical benefit, yet toxicity and immunosuppression remain major obstacles. These limitations illustrate the pressing need for new strategies that unleash the immune system against tumours, but in a more controlled, safe, and durable manner.
In ARTimmune we pursued a radically different approach: the development of fully synthetic immune niches. These are engineered microenvironments designed to locally instruct immune cell function, generate bursts of cytotoxic T cells for tumour destruction, and at the same time avoid the systemic side effects seen with conventional immunotherapies.
We exploited advanced chemical tools to construct polymer-based scaffolds decorated with immune-modulating molecules. These immunofilaments are semiflexible polyisocyanopeptide (PIC) polymers coupled to antibodies, cytokines, or peptide–MHC complexes. We demonstrated that immunofilaments were highly effective in activating and expanding human and mouse T cells ex vivo, including tumour-specific and CAR-T cells. Importantly, immunofilaments retained full bioactivity of their cargo and provided a dynamic interface that better mimicked natural antigen-presenting cells (APCs).
As a next step, immunofilaments were immobilised on beads to form immunobrushes, creating a synthetic cell-like surface. These immunobrushes outperformed rigid benchmark systems, driving efficient expansion of T cells even at very low antibody density. They were capable of selectively expanding rare tumour-specific T cells present at <0.001% of total lymphocytes, demonstrating remarkable sensitivity and clinical potential.
To extend this concept to tissue niches, we developed 3D cryogel scaffolds based on hyaluronic acid (HAGM). These porous, semi-rigid matrices can be injected through a needle, after which they regain their shape and provide a local niche for immune cells. We showed that cryogels could harbour large numbers of T cells, maintain their viability, and promote multifunctional activation with reduced exhaustion. When preloaded with T cells, scaffolds retained them after injection in vivo, while also allowing infiltration of endogenous immune cells.
In vivo validation was an essential component of ARTimmune. Radiolabelled immunofilaments distributed to lymphoid organs and were well tolerated with no observable toxicity. In mouse tumour models, even a single injection of antigen-specific immunofilaments significantly inhibited tumour growth and metastasis formation. Cure rates reached 50%, and survival increased to 75% when combined with immune checkpoint blockade. These results underline the therapeutic promise of synthetic immune niches as stand-alone or combination therapies.
In summary, ARTimmune has demonstrated that it is feasible to mimic essential immune cell functions using synthetic, immune-reactive polymers. Immunofilaments, immunobrushes, and cryogel scaffolds all proved capable of potently activating and expanding tumour-reactive T cells. These findings open the door to a new class of biomaterial-based immunotherapies that move beyond systemic maximum-tolerated-dose regimens with high toxicity, towards local, modular, and low-dose interventions that might nonetheless induce systemic tumour immunity.
