Active immunization with a structurally aggregated PD-L1 antigen breaks T and B immune tolerance in non-human primates and exhibits in vivo anti-tumoral effects in immunocompetent mouse tumor models

• Published in: Cancer letters Vol. 561; p. 216156
• Main Authors: Morera-Díaz, Y., Canaán-Haden, C., Sánchez-Ramírez, J., Bequet-Romero, M., Gonzalez-Moya, I., Martínez, R., Falcón, V., Palenzuela, D., Ayala-Ávila, M., Gavilondo, J.V.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.05.2023
• Subjects: Animals; B-Lymphocytes - immunology; B7-H1 Antigen; CD8-Positive T-Lymphocytes; Humans; Immune checkpoint; Immune Tolerance; Immunotherapy; Immunotherapy - methods; Mice; Neoplasms - therapy; PKPD-L1; Primates - metabolism; Tumor Microenvironment; Vaccination; Immune checkpoint; Tumor microenvironment; Immunotherapy; PKPD-L1
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2023.216156

Despite the clinical success of the programmed death ligand 1 (PD-L1) blocking therapy in cancer treatment, only a subset of patients exhibits durable responses, therefore further exploration of other immunotherapeutic alternatives are needed. This paper reported the development of the PKPD-L1Vac vaccine, a new protein vaccine candidate that uses aluminum phosphate as an adjuvant and as an antigen the extracellular domain of human PD-L1 fused to a 47 amino-terminal portion of the LpdA protein from N. meningitides (PKPD-L1). The PKPD-L1 antigen has different physical and biological characteristics than those found in the natural molecule and in others PD-L1 vaccine candidates. The quimeric protein has a reduced binding capacity to the PD-1 and CD80 receptors to decrease their pro-tumoral activity. Besides, the distinctive feature of the PKPD-L1 polypeptide to be structurally aggregated could be desirable for its immunogenic properties. PKPD-L1Vac elicited anti-PD-L1-specific IgG antibodies and T lymphocyte-mediated immunity in mice and non-human primates. The vaccine administration demonstrated antitumor activity on CT-26 and B16–F10 primary tumor models in mice. Moreover, the immunization with PKPD-L1Vac increased the tumor-infiltrating lymphocytes and decreased the proportion of CD3+CD8+PD1+high anergic T cells in CT-26 tumor tissues, suggesting that the vaccine may remodel the tumor microenvironment. In summary, the PKPD-L1Vac vaccine exhibits very promising preclinical results and deserves to move forward to a phase I clinical trial. •PKPD-L1Vac uses as an antigen the extracellular domain of human PD-L1 fused to a portion of the LpdA protein from N. meningitides.•PKPD-L1 antigen has a reduced binding capacity to their receptors to decrease their potential pro-tumoral activity.•PKPD-L1Vac elicited anti-PDL1-specific IgG antibodies and T lymphocyte-mediated immunity in mice and non-human primates.•PKPD-L1Vac administration demonstrated antitumor activity on CT-26 and B16–F10 primary tumor models in mice.