AGI-134 is a synthetic alpha-Gal glycolipid in development for solid tumors that is highly differentiated from other cancer immunotherapies. AGI-134 is designed to label cancer cells with alpha-Gal via intra-tumoral administration, thereby targeting the body’s pre-existing, highly abundant anti-alpha-Gal (anti-Gal) antibodies and redirecting them to treated tumors. Binding of anti-Gal antibodies to the treated tumors results in activation of the complement cascade, which destroys the tumor cells and creates a pro-inflammatory tumor microenvironment that also induces a systemic, specific anti-tumor (vaccine) response to the patient’s own tumor neo-antigens.
a Intratumoral injection of AGI-134 and coating of tumor cells
b Binding of anti-Gal antibodies
c Initial cell death and release of tumor-associated antigens
d Increased uptake by antigen presenting cells and alteration of tumor microenvironment
Efficient cross-presentation to effector T cells
a Tumor cell destruction
b Stimulation & recruitment of T cells
Tumor cell destruction
AGI-134 is injected into the tumor, where it coats the tumor cell membranes, resulting in αGal being exposed on the tumor cell surface. Endogenous anti-Gal antibodies bind to the αGal part of AGI-134 to produce an initial immune response that activates complement-dependent and antibody-dependent cellular cytotoxicity (cell death). This cytotoxicity generates immune-tagged cells and cellular debris that trigger an uptake of tumor-associated antigens by antigen-presenting cells (APCs). These APCs induce a follow-on systemic immune response by the activation and clonal expansion of T cells (CD8+) to the patient’s own neo-antigens. This approach not only targets the primary injectable tumor, but has also demonstrated efficacy against existing distant secondary tumors. Furthermore, the mechanism of action suggests the potential of long-term protection against future metastases.