Active immunotherapy based on a structural variant of programmed death receptor 1 ligand 1
Keywords:
Immunotherapy; Tumor microenvironment; PD-L1; Immune checkpointAbstract
Introduction: Immune checkpoint inhibitors have led to a paradigm shift in cancer treatment. In this context, active immunotherapy represents a promising approach for tumor therapy targeting this molecule.
Objectives: To develop a vaccine based on a structural variant of human PD-L1 capable of inducing a specific immune response with antitumor effects, and to study the immune effectors involved and their impact on the tumor microenvironment.
Methods: The preclinical development of PKPD-L1Vac included the following stages: in silico design of the antigen; expression in E. coli; physicochemical characterization; evaluation of immunogenicity in mice and non‑human primates; and assessment of antitumor activity in murine models.
Results: A chimeric antigen derived from the extracellular domain of human PD-L1 was generated, featuring structural modifications that reduce its binding affinity to PD-1 and CD80. The vaccine induced specific anti‑PD‑L1 IgG antibodies and T cell‑mediated immunity in both mice and non‑human primates. It demonstrated antitumor activity in CT‑26 and B16‑F10 models. Additionally, it increased tumor‑infiltrating lymphocytes in CT‑26 tumors and reduced the proportion of anergic CD3+CD8+PD1+ T cells.
Conclusions: These results provide proof of concept for a novel vaccine based on a modified PD‑L1 variant that elicits a potent immune response with effective antitumor activity across multiple syngeneic mouse models, as well as the breaking of immunological tolerance to human PD‑L1 in a phylogenetically close model.
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Copyright (c) 2026 Camila Canaán-Haden Ayala, Javier Sánchez Ramírez, Mónica Bequet Romero, Isabel Gonzalez-Moya, Rafael Martínez Castillo, Viviana Falcón Cama, Daniel Octavio Palenzuela Gardon, Miladys Limonta Fernández, Marta Ayala Ávila, Jorge V. Gavilondo Cowley, Yanelys Morera Díaz
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