On April 29, 2022 Elicio Therapeutics, a clinical-stage biotechnology company developing a pipeline of novel immunotherapies for the treatment of cancer and other diseases, reported that it is presenting preclinical data demonstrating robust and durable anti-tumor responses by combining its Amphiphile (AMP) platform vaccine, carrying cognate peptide and adjuvant cargos, with T cell receptor T cell therapies (TCR-Ts) (Press release, Elicio Therapeutics, APR 29, 2022, View Source [SID1234613254]). AMP cognate peptides traffic to the lymph nodes and are presented by activated antigen-presenting cells to improve TCR-T cell persistence and anti-tumor function. The data is being presented at the 2022 Keystone Symposia on Emerging Cellular Therapies virtually and in-person in Keystone, CO from April 27-May 1, 2022. The electronic presentation is accessible here.

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"The efficacy of TCR-Ts in solid tumors has been promising but limited by challenges related to suboptimal T cell expansion, persistence and function as well as poor tumor infiltration and antigen escape. These data are particularly exciting because we have shown that TCR-Ts in combination with our AMP-vaccination platform can address each of these issues," said Peter DeMuth, Ph.D., Chief Scientific Officer at Elicio Therapeutics. "By targeting AMP-peptide vaccination directly to the lymph nodes, we can promote antigen presentation alongside numerous complementary mechanisms critical for potent TCR-T cell enhancement and broad immune activation. We’ve seen that this potent activation in the lymph nodes results in TCR-T cell persistence and robust anti-tumor function."

Robert Connelly, Elicio’s Chief Executive Officer, added, "The ability to enhance TCR-T clinical responses in solid tumors using the AMP platform supports our existing data across other immunotherapy platforms and indications, reinforcing the untapped potential of our lymph node-targeting strategy."

TCR-T therapies are similar to CAR-T therapies but differ in the types of receptors they use to recognize antigens. TCR-Ts utilize the intrinsic antigen recognition mechanisms of the T cell and can even recognize intracellular antigens which makes them a powerful tool to target solid tumors. While this unique mechanism has shown clinical anti-tumor efficacy, TCR-T cells still face challenges that Elicio hopes to address by boosting TCR-T cell therapy in the lymph nodes, the "brain center" of the immune system, with its AMP platform.

Presentation Details

Title: Lymph node-targeted boosting with cognate Amphiphile-peptide vaccines enhances TCR-T Cell therapy to eradicate solid tumors

Highlights from the Presentation:

AMP vaccination delivers cognate peptides and adjuvant to lymph nodes which induces dendritic cell activation and provides in vivo activation of tumor-specific TCR-T cells to amplify, both in quantity and function, the anti-tumor potency of adoptively transferred cells.
AMP vaccination significantly enhanced TCR-T cell anti-tumor response while also inducing epitope spread among endogenous T cell population, leading to durable cures of solid tumors in an established, syngeneic tumor model.
Vaccination with AMP-mKRAS peptides in mice expressing human leukocyte antigen A*11:01 (HLA A*11:01) significantly enhanced the activation, persistence and specific target lysis of murine mKRAS-specific TCR-T cells.
AMP-peptide pulsed autologous human dendritic cells enhanced the function of several clinically relevant tumor-targeted human TCR-modified T cells in vitro including those targeting mKRAS, HPV16 E7 and NY-ESO-1.
These studies provide direct rationale and evidence for the combination of AMP vaccination with TCR-T cell therapies to augment clinical responses.
About the Amphiphile Platform

Our proprietary Amphiphile, or AMP, platform delivers investigational immunotherapeutics directly to the "brain center" of the immune system – the lymph nodes. We believe this site-specific delivery of disease-specific antigens, adjuvants and other immunomodulators may efficiently educate, activate and amplify critical immune cells, potentially resulting in induction and persistence of potent adaptive immunity required to treat many diseases. In preclinical models, we have observed lymph node-specific engagement driving therapeutic immune responses of increased magnitude, function and durability. We believe our AMP lymph node-targeted approach will produce superior clinical benefits compared to immunotherapies that do not engage the lymph nodes.

Our AMP platform, originally developed at the Massachusetts Institute of Technology, or MIT, has broad potential across cancers, infectious diseases and other disease indications to advance a number of development initiatives through internal activities, in-licensing arrangements or development collaborations and partnerships.

The Amphiphile platform has been shown to deliver immunotherapeutics directly to the lymph nodes by latching on to the protein albumin, found in the bloodstream, as it travels to lymphatic tissue. In preclinical models, we have observed lymph node-specific engagement driving therapeutic immune responses of increased magnitude, function and durability.