Abstract 3542: Nanofilament immunotherapy as an antigen-agnostic cancer vaccine

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Checkpoint inhibitors revolutionized cancer treatment by potentiating antitumor immune responses. However, many patients do not respond to these therapies, often due to a lack of pre-existing immune response against cancer cells. Personalized cancer vaccines promote cancer cell antigen recognition and mount antitumor immune responses, thus helping to improve response rates. However, personalized cancer vaccine interventions imply complex and costly procedures that make the technology difficult to scale. As an alternative to personalized cancer vaccines, we established multimodal nanofilament immunotherapy as an antigen-agnostic in situ cancer vaccine modality. Through genetic engineering of the M13 bacteriophage, nanofilaments displaying combinations of therapeutic agents were generated to steer the immune system against cancer cells. TAT003, a multimodal nanofilament combining the natural adjuvant properties of M13 with the display of anti-PD-L1 and IL-2 molecules, was developed to bind the surface of cancer cells and transform them into immunological targets. After validation of TAT003 biological activities in vitro and assessment of biodistribution, the potency of the candidate was evaluated upon intratumoral administration in syngeneic mouse models both as a single agent as well as in combination with PD-1 blockade therapy. The mode of action of TAT003 was also characterized using cytokine paneling, immune profiling, and T-cells activation assays. TAT003 nanofilaments simultaneously displayed biologically active anti-PD-L1 and IL-2 molecules. Upon intratumoral injection, TAT003 anchored durably in the tumor, which limited systemic exposure to the drug. TAT003 profoundly remodeled the tumor microenvironment of injected lesions, where it sparked a strong myeloid cell infiltration, and promoted the infiltration of T-cells in non-injected contralateral lesions, promoting T-cells infiltration. This translated into potent tumor regression of both lesions in multiple cancer models, and potentiated PD-1 blockade therapy. TAT003 treatment induced the expansion of cancer-cell specific effector T cells systemically, providing a long-lasting antitumor vaccine response. Multimodal nanofilament immunotherapy is a novel approach to mount systemic antitumor immune responses in situ by physically coupling large immunostimulatory molecules to cancer cells. TAT003 induced marked tumor regressions by leveraging synergies between the therapeutic agents displayed on its surface while offering a favorable tolerability profile. These results establish multimodal nanofilaments as an innovative and versatile immunotherapy platform for developing in situ cancer vaccines. Citation Format: Kevin Neil, Samuel Génier, Marie-Ève Poisson, Hugo Giguère, Lauren Daniel, Julie Douchin, Lee-Hwa Tai, Sébastien Rodrigue, Jean-François Millau. Nanofilament immunotherapy as an antigen-agnostic cancer vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3542.

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