{
  "abstract": "Background Cervical cancer, driven by persistent high-risk HPV infection, accounts for more than 660,000 new cases and 348,000 deaths worldwide each year. 1 2 Late-stage cervical cancer is frequently resistant to immune checkpoint inhibitors and carries a five-year overall survival <17%.3 4 Within this immunosuppressive microenvironment, HPV oncoproteins contribute to tumor immune evasion but also provide highly antigenic targets for intervention. Intratumoral delivery represents a strategic opportunity to overcome local immune resistance, enhance tumor-specific cytotoxicity, and provoke systemic anti-tumor responses that also target metastatic lesions. However, conventional intratumoral approaches often fail due to rapid drug leakage, insufficient retention, and inadequate immune activation.5 To address these limitations, we developed ABS001, an intratumoral immunomodulatory delivery platform containing imiquimod engineered for prolonged retention, targeted distribution, and sustained immune stimulation across the tumor-immune interface. Here, we demonstrate that a single intratumoral administration of ABS001 induces both innate and adaptive immune responses.Methods ABS001 was evaluated in two models: a non-HPV murine tumor model to establish proof-of-principle, and an HPV-driven cervical cancer model. ABS001 was administered intratumorally at 10- or 17-days post-tumor inoculation, respectively. Tumors, spleens, and draining lymph nodes were harvested at 1-, 3-, and 7-days post-treatment. Tissues were analyzed by flow cytometry to assess myeloid and lymphocyte activation and infiltration. Additionally, a dose-response study was conducted using low-, mid-, and high-dose formulations of ABS001 to explore potential bell-shaped immunologic effects.Results In the longitudinal study, we observed robust dendritic cell (DC) and macrophage activation at 1 and 3 days post-ABS001 administration, evidenced by increased CD80 and CD86 positivity. The dose-response experiment revealed a bell-shaped curve, with intermediate imiquimod doses producing the most pronounced DC and macrophage activation at day 3. Within the tumor microenvironment, a significant increase in the intratumoral CD8/CD4 T cell ratio was detected at 7 days post-ABS001 administration compared to untreated controls. This enhancement followed a similar bell-shaped pattern, with maximal T cell infiltration occurring at intermediate doses.Conclusions Our findings demonstrate that ABS001 enables sustained retention of its immunomodulatory payload and robust activation of innate and adaptive immune responses following a single intratumoral administration. Importantly, the intermediate dose achieved the most potent immune activation and T cell infiltration into the tumor, underscoring the value of dose optimization. Taken together, these data highlight ABS001’s potential as a highly targeted and effective immunotherapy platform for cervical cancer and with potential in other solid tumors with an immunosuppressive microenvironment.References Wei F, Georges D, Man I, Baussano I, Clifford GM. Causal attribution of human papillomavirus genotypes to invasive cervical cancer worldwide: a systematic analysis of the global literature. The Lancet. 2024;404(10451):435–444.Amiri S, Rasekh S, Moezzi SMI, Seifi N, Fatemi SA, Fathi S, Negahdaripour M. Prophylactic vaccines against HPV-caused cervical cancer: novel vaccines are still demanded. Infectious Agents and Cancer. 2025;20(1):16.Tewari KS. Cervical cancer. New England Journal of Medicine. 2025;392(1):56–71.Monk BJ, Enomoto T, Kast WM, McCormack M, Tan DS, Wu X, González-Martín A. Integration of immunotherapy into treatment of cervical cancer: recent data and ongoing trials. Cancer Treatment Reviews. 2022;106:102385.Som A, Rosenboom JG, Chandler A, Sheth RA, Wehrenberg-Klee E. Image-guided intratumoral immunotherapy: developing a clinically practical technology. Advanced Drug Delivery Reviews. 2022;189:114505.Ethics Approval The Animal Use Protocol was approved by SmartLabs’ Institutional Animal Care and Use Committee and Institutional Biosafety Committee.",
  "authors": [
    {
      "affiliations": [
        "Absco Therapeutics, Inc., Allston, MA, USA"
      ],
      "name": "Gil Covarrubias"
    },
    {
      "affiliations": [
        "Absco Therapeutics, Inc., Allston, MA, USA"
      ],
      "name": "Rebekah Garfolo"
    },
    {
      "affiliations": [
        "Absco Therapeutics, Inc., Allston, MA, USA"
      ],
      "name": "Stephen W Linderman"
    },
    {
      "affiliations": [
        "Absco Therapeutics, Inc., Allston, MA, USA"
      ],
      "name": "David H Altreuter"
    },
    {
      "affiliations": [
        "Absco Therapeutics, Inc., Allston, MA, USA"
      ],
      "name": "Julienne Teich"
    }
  ],
  "title": "1004 ABS001: a retention-optimized intratumoral immunotherapy eliciting robust innate and adaptive responses in HPV and non-HPV tumors",
  "uid": "578f660a-308d-52f0-b08b-d9268247e6b6"
}