Elicio Therapeutics: Shaping the Future of Immunotherapy

Immunotherapy has transformed cancer treatment by harnessing the immune system to fight disease. However, many therapies struggle with efficiency and durability, limiting their impact. Innovative approaches are needed to enhance immune activation and sustain long-term protection against tumors.

Elicio Therapeutics is developing strategies to improve immunotherapy outcomes by optimizing antigen delivery and targeting key areas of the immune system to create stronger, lasting responses.

Antigen Presentation Concepts

The immune system’s ability to recognize and eliminate threats depends on antigen presentation, which dictates how immune cells detect and respond to abnormal proteins. This process is primarily managed by antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells. These cells process and display antigens on their surface using major histocompatibility complex (MHC) molecules, determining the strength and specificity of the immune response.

MHC molecules are divided into two classes. MHC class I molecules present endogenous antigens—derived from intracellular pathogens or mutated proteins—to CD8+ cytotoxic T cells, which initiate targeted cell destruction. MHC class II molecules display exogenous antigens—originating from extracellular pathogens or vaccine components—to CD4+ helper T cells, which activate other immune effectors, including B cells and macrophages. Balancing these pathways is crucial for mounting an effective defense while preventing excessive immune activation that could lead to autoimmunity.

Many tumors evade detection by downregulating MHC expression or secreting immunosuppressive factors that impair APC function. To counteract this, researchers are developing strategies to enhance antigen presentation, such as engineering synthetic peptides that bind more effectively to MHC molecules or utilizing adjuvants that stimulate APC maturation. For example, toll-like receptor (TLR) agonists can enhance dendritic cell activation, leading to improved antigen presentation and stronger T cell priming.

Elicio Therapeutics is refining antigen presentation by designing constructs that optimize MHC binding and stability, improving immune recognition. Their approach also considers the spatial and temporal dynamics of antigen presentation, ensuring immune cells encounter antigens in a way that maximizes activation potential. This is particularly relevant in tumors, where antigen availability and immune accessibility are often limited.

Lymph Node Targeting Platforms

Lymph nodes serve as hubs for immune coordination, where antigen-presenting cells interact with lymphocytes to initiate and refine immune responses. Given their role in immune surveillance, they are an attractive target for immunotherapy. However, delivering antigens and adjuvants to lymph nodes with precision remains a challenge. Traditional vaccine and immunotherapy approaches often rely on passive diffusion, leading to suboptimal lymph node accumulation and reduced immunogenicity.

Elicio Therapeutics has developed lymph node-targeting platforms to enhance antigen delivery and retention. This strategy uses amphiphilic carriers that exploit endogenous transport mechanisms for efficient lymph node trafficking. These carriers incorporate lipid moieties that enable binding to albumin, a serum protein with a high affinity for lymphatic transport. By leveraging albumin’s role in molecular distribution, these engineered constructs gain preferential access to the lymphatic system, ensuring antigens reach their intended destination more effectively. Studies have shown that albumin-binding vaccine components can significantly increase lymph node accumulation and immune activation.

Beyond improving antigen localization, these platforms extend antigen retention within lymphoid tissues, allowing for prolonged interactions between antigen-presenting cells and lymphocytes. This extended exposure is crucial for generating robust immune responses, facilitating repeated antigen encounters and the formation of immunological synapses necessary for signal transduction. Preclinical models have shown that lymph node-targeting formulations can sustain antigen presentation over several days, leading to higher frequencies of antigen-specific T cells and greater overall immunogenicity.

Elicio Therapeutics is also refining antigen uptake and processing within lymph nodes. By adjusting the physicochemical properties of their constructs—such as charge, hydrophobicity, and molecular size—they can influence how antigens interact with lymphatic endothelial cells and resident APCs. For example, nanoparticle-based systems with controlled surface modifications have been shown to enhance uptake by dendritic cells, improving antigen cross-presentation. These refinements enable more precise immune activation, reducing off-target effects while maximizing therapeutic efficacy.

Coordinated T And B Cell Engagement

A durable and highly specific immune response requires coordination between T and B cells, two interconnected arms of adaptive immunity. Cytotoxic T cells target and eliminate abnormal cells, while B cells produce antibodies that neutralize extracellular threats. Immunotherapy is more effective when these two cell types are activated in a synchronized manner, ensuring a multi-faceted defense that eliminates malignant cells and prevents recurrence.

This interaction occurs within germinal centers in lymphoid tissues, where high-affinity antibody-producing B cells mature under the guidance of helper T cells. Follicular helper T cells (Tfh) play a key role by providing survival and differentiation signals to B cells via cytokines such as IL-21 and co-stimulatory molecules like CD40L. Without this support, B cells fail to undergo the necessary affinity maturation for producing potent, long-lasting antibodies.

Elicio Therapeutics is enhancing Tfh cell activation alongside cytotoxic T cell responses to create a more comprehensive defense against cancer. Their immunotherapies stimulate robust T cell priming while promoting B cell recruitment and expansion within germinal centers. This ensures both cellular and humoral immunity are reinforced, reducing the likelihood of tumor escape mechanisms that exploit gaps in immune surveillance.

Immune Memory Formation

Long-term immunity depends on the immune system’s ability to “remember” past encounters, enabling a faster, more effective response upon re-exposure. Immunological memory is established through specialized memory T and B cells, which persist long after initial activation. Unlike short-lived effector cells that decline once a pathogen or malignant cell population is cleared, memory cells can last for years, providing lasting protection.

Elicio Therapeutics is optimizing conditions for memory T and B cell development. The differentiation of memory T cells is influenced by antigen persistence, inflammatory signals, and cytokine environments, all of which shape their functional properties. Central memory T cells (T_CM) reside in lymphoid tissues, where they undergo homeostatic proliferation, while effector memory T cells (T_EM) patrol peripheral tissues, ready to launch immediate responses. By fine-tuning antigen exposure and immune-stimulatory cues, Elicio aims to promote a balanced memory response that ensures both long-term surveillance and rapid effector function.