Vaccine composition and uses thereof
Inventors
Ede, Nicholas • Wiedermann, Ursula • Tobias, Joshua • Zielinski, Christoph
Assignees
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Publication Number
US-12311019-B2
Publication Date
2025-05-27
Expiration Date
Abstract
Disclosed herein is a vaccine composition for raising a humoral response to PD1, and uses thereof, for treating a cancer characterised by an involvement of PD1, wherein the vaccine composition comprises an effective amount of an immunogen that induces an antibody response in which the antibody binds to a B cell epitope of PD1.
Core Innovation
The disclosure relates to a PD1-targeting vaccine that induces an antibody response against PD1 B-cell epitopes. It uses short peptide immunogens comprising B cell epitopes of PD1, where the B cell epitope consists of amino acid sequences selected from specified SEQ ID NOs, including combinations of two or more of the foregoing. The immunogen sequence is not identical to a continuous stretch of at least 50 amino acid residues of PD1.
The antibody response is humoral, and antibodies elicited by the peptide immunogens bind native PD1. The disclosure reports that antibodies elicited by these peptides inhibit PD1/PD-L1 binding and are associated with reduced tumor growth in mice. It also reports absence of adverse effects in the mouse immunization.
The document further describes immunogen formats and compositions for raising a humoral response to PD1. It includes single peptides or fusion constructs with multiple epitopes, functional variants with ≥70% sequence identity, optional inclusion of a promiscuous T helper epitope, and vaccine components including carriers and adjuvants, as well as evaluation of cross-species binding and cross-reactivity of anti-PD1 antibodies.
Claims Coverage
The partial claim set includes two independent claims: one directed to a method of treating cancer by administering a PD1 epitope vaccine composition, and one directed to the vaccine composition itself. Across the two independent claims, there are three core inventive elements.
Treating cancer with a PD1 B cell epitope vaccine inducing PD1-binding antibodies
Administering to a human subject having a cancer characterized by an involvement of PD1 a vaccine composition comprising an effective amount of an immunogen that induces an antibody response in which the antibody binds to a B cell epitope of PD1, wherein the immunogen comprises a B cell epitope of PD1 consisting of an amino acid sequence selected from SEQ ID NOs: 9, 10, 14, 24, 28, 29, 42, 43, 49, and a combination of two or more of the foregoing, and wherein the amino acid sequence of the immunogen is not identical to a continuous stretch of at least 50 amino acid residues of PD1.
Vaccine composition with a PD1 B cell epitope immunogen for raising a humoral response
A vaccine composition for raising a humoral response to PD1 comprising an immunogen that induces an antibody response in which the antibody binds to a B cell epitope of PD1, wherein the immunogen comprises a B cell epitope of PD1 consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 9, 10, 14, 24, 28, 29, 42, 43, and 49, and a combination of two or more of any of the foregoing, wherein the amino acid sequence of the immunogen is not identical to a continuous stretch of at least 50 amino acid residues of PD1, and wherein the vaccine composition further comprises an adjuvant.
Both independent claims center on immunogens that present PD1 B cell epitopes defined by specified SEQ ID NO amino acid sequences, including combinations, to induce an antibody response that binds PD1, while requiring that the immunogen sequence is not identical to a continuous stretch of at least 50 amino acid residues of PD1. The composition claim additionally requires the presence of an adjuvant.
Stated Advantages
Antibodies elicited by the peptide immunogens bind native PD1.
Antibodies elicited by these peptides inhibit PD1/PD-L1 binding.
Reduced tumor growth in mice.
Absence of adverse effects in the mouse immunization.
Documented Applications
Treating a cancer in a human subject characterized by an involvement of PD1 using a PD1 B cell epitope vaccine composition.
Raising a humoral response to PD1 with a vaccine composition comprising a PD1 B cell epitope immunogen and an adjuvant.
Evaluation of cross-species binding and cross-reactivity of anti-PD1 antibodies (mouse, rhesus, cynomolgus, canine, and rat).
Mouse immunization in a syngeneic mouse tumor model with reported reduced tumor growth (D2F2/E2).
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