Amphiphile CAR-T Therapy

Powerfully amplifying
CAR-T cells in the lymph nodes


Engineered cell therapies such as Chimeric Antigen Receptor T cells (CAR-T) have emerged as a powerful therapeutic strategy for cancer treatment with demonstrated efficacy in leukemia and lymphoma.  In this approach, T cells collected from a patient are genetically reprogrammed to express surface receptors (CARs) which allow them to specifically recognize tumors.  Patients are given large doses of these CAR-expressing T cells which search out tumor cells throughout the body using their CAR to differentiate healthy cells from tumor.  This specific recognition process between the CAR and the tumor triggers T cell activation and tumor cell killing.

For certain forms of cancer, CAR-T cell therapy has completely eliminated tumors allowing patients to live disease free lives. However, in most settings, the efficacy of CAR-T cells has been limited by factors such as poor persistence and limited anti-tumor functionality. Achieving the full promise of this approach, especially in solid tumors, will require further advances to enhance efficacy by boosting anti-tumor activity and persistence of CAR-T cells. The AMP-CAR-T platform is based on the use of Amphiphile activators to engage these CAR-T cells in the lymph node to stimulate potent activation, expansion, and functional enhancement using the full power of immunological signaling only present in this specialized site.

The Amphiphile platform has been designed using fatty acids to take advantage of the natural lymph targeting properties of albumin to accumulate in lymph nodes. In parallel, these same fatty acids have been optimized to specifically insert into cell membranes to enable presentation as cell-surface bound molecules. When presented on the surface of immune cells in the lymph node, these AMP-CAR-T activators are detected by neighboring cells as cues to activate critical immunological pathways unlocking the full anti-tumor activity of stimulated cells.

Amphiphile structures contain specially designed fatty acids to deliver signals to lymph nodes and present them on the surface of immune cells.

When combined with CAR-T therapy, AMP-CAR-T activators specifically designed to bind to the CAR receptor are presented on the cell surface of immune cells in the lymph node. CAR-T cells migrating through the lymph nodes on their way to the tumor see these AMP-CAR-T activators on the surface of antigen presenting cells (APCs), specialized immune cells which deliver activating signals to T cells to coordinate their expansion and mobilization against tumors. The cell surface presentation of AMP-CAR-T activators in combination of an array of other stimulatory molecules naturally present on APCs delivers a combination of potent activating cues to the CAR-T cells, significantly boosting their numbers and anti-tumor functionality before deploying them throughout the body to seek and destroy tumor.

CAR-T cells are engineered, expanded, and delivered to patients where they are amplified by AMP-CAR-T activators in the lymph nodes to expand their numbers and enhance their anti-tumor functionality.

By using Amphiphiles to deliver tunable activating signals to CAR-T cells the lymph node is transformed into a command center for the anti-tumor immune response, where the T cell ranks are multiplied, equipped, and supported on their mission to defeat cancer.  This strategy is highly flexible for universal application with any CAR-T therapy without the need for re-engineering of the CAR-T cell design.  Elicio is utilizing powerful discovery methods to design tunable AMP-CAR-T activators to boost CAR-T cell therapies in a variety of settings including those targeting CD19, BCMA, and several solid tumor indications.

 

AMP-CAR-T activators transform the lymph nodes into a command center for the anti-tumor immune response, where the CAR-T cell ranks are multiplied, equipped, and supported on their mission to defeat cancer.

Current CAR-T cell therapies are challenging and expensive to manufacture, requiring extensive laboratory manipulation of T cells collected from patients to generate a pool of CAR-T cells large enough to be effective when transferred back into the patient. The AMP-CAR-T approach provides a short-cut to this costly and time-consuming process. Instead of expanding and activating large numbers of CAR-T cells artificially outside the body, AMP-CAR-T activators reprogram the lymph nodes into highly efficient CAR-T cell-producing factories, allowing a small number of CAR-T cells to be expanded and activated inside the body’s natural centers of immune activity. This approach has the potential to solve many of the practical challenges facing CAR-T, allowing for shorter, less expensive manufacturing cycles and more reliable delivery of this life-saving therapy to patients.