Targeted and powerful
The Amphiphile platform has been developed and optimized through extensive preclinical testing and validation in the labs at MIT and Elicio. These studies have demonstrated efficient and precise lymph node targeting in mice and non-human primates, where Amphiphiles accumulate broadly in multiple lymph nodes after injection and persist at levels more than 10 times greater than possible through conventional approaches. This improvement in lymph node targeting has resulted in more than a 50-fold enhancement in the delivery of Amphiphile immunogens to immune cells, compared to traditional immunogens. In tests targeting several models of aggressive cancer in mice, Amphiphile vaccines have elicited endogenous cancer-specific immune responses of unprecedented potency, more than 30 times greater than conventional immunogens can achieve. This has resulted in eradication and durable cures of advanced tumors with immune-memory mediating complete protection against future secondary challenge.
In combination with engineered anti-tumor immune cells such as CAR-T cells, AMP-CAR-T activators have elicited massive expansion (greater than 1,000-fold) of effector immune cells in the lymph nodes following administration to mice. In preclinical studies, amplifying CAR-T cells in the lymph nodes generated potent immunological signaling through an extensive array of endogenous costimulatory molecules to maximize CAR-T cell expansion, and development of anti-tumor effector functions. In addition to driving expansion and activation of tumor-targeting immune cells, Amphiphile-driven immune activation in the lymph nodes generates CAR-T cells with greatly enhanced solid tumor infiltration. Relative to CAR-T cells given without AMP-CAR-T activation, circulating and tumor-infiltrating CAR-T cells demonstrate significantly improved anti-tumor functionality including enhanced polyfunctional cytokine secretion, cytolytic activity, and proliferative phenotype. When used to treat a variety of aggressive solid tumors in mice, the combination of AMP-CAR-T activators with CAR-T cell therapy produced significantly delayed tumor growth and complete durable cures where CAR-T cells alone had no therapeutic effect. The AMP-CAR-T-activated T cell responses were also highly durable yielding complete long-term protection against relapse in cured animals months after initial treatment. AMP-CAR-T activation of CAR-T cells also produced potent induction of endogenous immune responses against other untargeted tumor antigens, a potentially critical factor for enabling therapeutic efficacy and long term protection against antigenically heterogeneous tumors.