{
  "abstract": "Background The development of immunotherapies in oncology is a substantial advancement in the targeted treatment of cancer. Promising outcomes have been achieved with antibodies, CAR-T, tumor-infiltrating lymphocytes, and therapeutic cancer vaccines. However, in most cases, these approaches involve time-consuming identification of tumor-specific neo-antigens, as well as complicated and lengthy manufacture, generally yielding patient-specific products. To circumvent these challenges and limitations, in situ immunotherapy administers immunostimulatory adjuvants directly into tumors, where innate immune cell activation results in the processing of antigen from within the tumor itself. As this method enables unsupervised antigen selection by the immune system, this antigen-agnostic approach does not require specification or manufacturing of neo-antigens, and instead has the potential to generate comprehensive, polyclonal immunity against the complete heterogenic tumor antigen repertoire, reducing the risk of tumor immune evasion. Additional potential benefits of intratumoral immunotherapy are the decreased risk of systemic toxicity and the induction of local inflammation that could counter aspects of the immunosuppressive tumor microenvironment. Amphiphile (AMP)-CpG-7909 (ELI-004) is an ideal candidate in this context, as it has been designed to enhance tumor tissue retention by anchoring into cell membranes via its lipophilic AMP-tail.1 ELI-004 has been evaluated in multiple phase 1/2 trials (NCT04853017/NCT05726864) as part of an AMP-CpG-7909-adjuvanted peptide immunotherapy targeting mutant KRAS antigens (ELI-002). Data from the Phase 1 trial demonstrated potent T cell responses correlated with clinical outcome.Methods In this study, syngeneic tumor cells (e.g.: B16.F10) were transplanted subcutaneously into the flank of mice and allowed to establish tumors of ~50 mm 3 before treatment initiation. AMP-immunomodulators or vehicle only mock controls were injected intratumorally up to five times over a period of three weeks. Throughout the study, tumor growth and overall survival of mice were monitored.Results While mock treated tumors reached euthanasia criteria of 1000 mm 3 around day 25 after challenge, the average size of AMP-CpG-7909 treated tumors remained at 49 mm3 at that time. On day 42, ten days after the therapy phase concluded, tumor growth remained well controlled with 25% of mice achieving complete response and long-term non-progression, and no mice reaching euthanasia criteria. The 5 nmol AMP-CpG-7909 in situ treatment was well tolerated with no adverse safety observations.Conclusions Overall, these results demonstrate the potential for AMP-immunomodulators as promising off-the-shelf agents for in situ immunotherapy that is not patient-restricted or limited to specific tumor mutations and can induce potent cellular immune responses to control tumor growth.Reference Liu H, Kwong B, Irvine DJ. Membrane anchored immunostimulatory oligonucleotides for in vivo cell modification and localized immunotherapy†. ` Angew. Chem. Int. Ed. 2011;50:7052–7055.",
  "authors": [
    {
      "affiliations": [
        "Elicio Therapeutics, Boston, MA, USA"
      ],
      "name": "Martin Steinbuck"
    },
    {
      "affiliations": [
        "Elicio Therapeutics, Boston, MA, USA"
      ],
      "name": "Mimi M Jung"
    },
    {
      "affiliations": [
        "Elicio Therapeutics, Boston, MA, USA"
      ],
      "name": "Erica Palmer"
    },
    {
      "affiliations": [
        "Elicio Therapeutics, Boston, MA, USA"
      ],
      "name": "Peter C DeMuth"
    }
  ],
  "title": "946 Amphiphile (AMP)-immunomodulator therapy controls growth and eradicates syngeneic solid tumors",
  "uid": "6039bbe6-f416-5a58-9d00-673fc40fecb8"
}