Elicio Therapeutics Submits IPO Prospectus Highlighting AMP Peptide Vaccine in Combination with TCR-T Therapy for Eradication of Solid Tumors

Feb 19, 2024 13:44 CST Updated 13:44

Elicio Therapeutics

Developer of Novel Immunotherapy

CAR-TThe astonishing efficacy in treating blood tumors and the tremendous commercial success have placed cell therapy in the spotlight.TCR-TCell therapy follows closely behind in the treatment of solid tumors.has shown unprecedented potential in aspects, with itsCapable of targeting multiple antigens within tumorsThe advantage has attracted more and more attention from industry giants. In2023By the end of the year,The world's first application for marketing approvalTCR-TCell Therapyafami-celComplete Rolling Submission, used for the treatment of advanced synovial sarcoma,In January 2024, the FDA officially announced the acceptance of this product.，This YearMay witness an important milestone in cell therapy shifting from hematologic tumors to solid tumors。

Recently, the team from biotechnology company Elicio Therapeutics published an article titled “Lymph Node–Targeted Vaccine Boosting of TCR T-cell Therapy Enhances Antitumor Function and Eradicates Solid Tumors"Research Article: Development of a Novel Immunotherapy Approach for Cancer Treatment by Combining Modified Amphiphilic Peptide Vaccines with TCR-T to Enhance the Immunotherapy Effect on Solid Tumors

TCR-T cell therapy has shown potential in treating various cancers, but its overall efficacy is limited due to the insufficient persistence and activation of T cells in the body, as well as potential tumor antigen escape.. To this end, the researchers proposed a new method by combiningAmphiphile（AMP）Peptide vaccination, including vaccines related to TCR-T cell-recognized peptide segments, enhances the persistence and function of TCR-T cells in vivo. AMP modification improves lymph node targeting by combining tumor immunogens and adjuvants, thereby orchestrating a robust endogenous immune response for T cell activation.

AMP Conjugated and Non-Conjugated Soluble SOL Peptide Sequences

They used a vaccine containing the epitope peptide and CpG adjuvant recognized by specific TCR-T cells in the diagram above, and combined it with TCR-T cell therapy.In mouse models, this combination therapy led to the complete eradication and durable responses of solid tumors that were unresponsive to TCR-T cell monotherapy.。

AMP Vaccination Enhances TCR T-Cell Therapy and Eradicates Established Solid Tumors

The combination of AMP vaccination and TCR-T cell therapy led to significant anti-tumor effects, which were associated with the simultaneous enhancement of the activation of transplanted TCR-T cells in vivo and the expansion of the endogenous anti-tumor T-cell repertoire.Long-term protection against tumor recurrence in mice is associated with the spread of antigens to other tumor-associated antigens after vaccination.Vaccination with AMP peptides is also associated with pro-inflammatory transcriptional reprogramming of lymph nodes and increased maturation of antigen-presenting cells, leading to the expansion and enhanced functionality of TCR-T cells within lymph nodes and the parenchyma of solid tumors without causing lymphocyte exhaustion.

Lymph nodes of mice vaccinated with AMP polypeptide can enhance TCR-T cell activation andIn vitroFunction

AMP Peptide Vaccine Inoculation Enhances the Infiltration of Activated and Proliferating TCR-T Cells, While Inducing Inflammatory Transcriptional Reprogramming and Epitope Increase in the Tumor Microenvironment

In vitro evaluation, compared with matched human TCR-T cells(Targeting NY-ESO-1, mutant KRAS, and HPV16 E7)The combined use of AMP-modified peptides demonstrated the clinical potential of AMP peptide vaccines to enhance the proliferation, activation, and anti-tumor activity of human TCR-T cells.

Clinical relevant human TCR-T cells with various specificities in vitro through AMPPeptide PulseBodyDC Enhanced Function, A-D：NY-ESO-1-specific human TCR-T cells (1G4) cultured with peptide-pulsed autologous DC, E-H:mKRAS-G12D Specific human TCR-T cells (701) cultured with peptide-pulsed autologous DC.

These preclinical data indicate that,The AMP vaccine, developed based on Elicio Therapeutics' Amphiphile Platform, can precisely deliver homologous peptides and adjuvants to lymph nodes, thereby inducing dendritic cell activation and promoting the in vivo activation of tumor-specific TCR-T cells to enhance the anti-tumor efficacy of adoptively transferred cells., which will bring widespread therapeutic benefits to many previously difficult-to-treat solid tumors, with the hope of completely eradicating solid tumors. A patent protection for this technology has been applied for.（EP4304638A1）。

The article also detailed the specific methods of the experiment, including vaccine components, animal models, cell lines, cell isolation and transduction, in vitro AMP-activated TCR-T cells, in vivo anti-tumor therapy, cell isolation for in vitro analysis, cell stimulation, cytotoxicity assays, Luminex cytokine production analysis, Nanostring gene expression analysis, flow cytometry, IVIS imaging, Elispot, and statistical analysis.

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