AGI-134 is a synthetic αGal immunotherapy in development for solid tumors. AGI-134 harnesses the body’s pre-existing, highly abundant, anti-αGal (anti-Gal) antibodies to induce a systemic, specific anti-tumor response to the patient’s own tumor neo-antigens. This response not only kills the tumor cells at the site of injection, but also brings about a durable, follow-on anti-metastatic immune response. αGal is a cell-surface carbohydrate antigen which is not expressed by humans, unlike virtually all other mammals and bacteria. Therefore, humans universally produce and maintain high levels of anti-Gal antibodies, due to exposure to αGal on bacteria in the digestive system.
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. 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.
We expect to commence a first-in-man study using AGI-134 in patients with solid tumors in 2018.