A Modular LOX-Mediated Delivery Platform for Solid Tumor Immunotherapy

SUMMARY

Enhanced tumor regression and immune activation through localized retention of engineered cytokines and chemokines by lysyl oxidase-mediated crosslinking to the tumor extracellular matrix improves therapeutic efficacy while reducing systemic toxicity.

The Unmet Need: Improving local retention and efficacy of immunotherapies within solid tumors

• Current immunotherapy approaches often suffer from limited drug accumulation within solid tumors, resulting in insufficient immune activation and systemic toxicities due to off-target effects. While checkpoint inhibitors have advanced cancer treatment, the inability to sustain therapeutic concentrations locally within the tumor microenvironment limits their full clinical potential.

• There is a growing industry focus on enhancing the spatial precision of biologics within solid tumors to boost efficacy and safety, aligning with trends in targeted delivery, tumor microenvironment modulation, and multifunctional engineered therapeutics.

The Proposed Solution: LOX-mediated covalent anchoring of engineered cytokines to tumor extracellular matrix for enhanced local immunotherapy

• The faculty inventor developed a technique fusing cytokines and chemokines with a lysyl oxidase substrate domain (LOD) that enables covalent crosslinking to the collagen- and elastin-rich tumor extracellular matrix by exploiting elevated lysyl oxidase activity in tumors. This modular platform generates therapeutic constructs such as LOD-IL-7 and LOD-IL-12, which accumulate and persist within tumor tissue, synergizing with checkpoint inhibitors to promote CD8⁺ T cell infiltration and effector differentiation.
• This method substantially reduces T cell exhaustion and induces robust anti-tumor immunity across multiple tumor models. Unlike conventional systemic cytokine delivery, this approach confines activity locally, decreasing systemic side effects and improving treatment durability. The technology has demonstrated preclinical validation in diverse tumor types and shows potential applicability in chronic inflammatory and fibrotic conditions.

ADVANTAGES

• Increased local retention of immunotherapeutics

• Reduced systemic toxicity and side effects

• Modular platform adaptable to multiple cytokines

• Enhanced CD8⁺ T cell tumor infiltration

• Synergistic effect with checkpoint inhibitors

APPLICATIONS

• Immunotherapy for solid tumors resistant to checkpoint blockade

• Enhancement of wound healing in diabetic and chronic wounds

• Therapeutic modulation of chronic inflammation and fibrotic diseases