Vaccine preparation containing trifunctional antibodies with antigen immunogenicity enhancer properties
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Publication Number
US-9750806-B2
Publication Date
2017-09-05
Expiration Date
Abstract
The present invention refers to a pharmaceutical composition containing trifunctional bispecific and/or trispecific antibodies being capable of binding to a specific target antigen(s) for use in a method of immunizing mammals against diseases in which said target antigen(s) is (are) involved, and further to a pharmaceutical composition containing trifunctional bispecific and/or trispecific antibodies being capable of binding to (a) specific target antigen (s) which is (are) involved in a disease of a mammal, specifically a human.
Core Innovation
The invention relates to an immunization approach using a trifunctional bispecific antibody and/or a trispecific antibody that binds to CD3 on T cells and activates the T cells. The same antibody also binds to a target antigen other than CD3, so that target antigen specificity is combined with T-cell activation within one antibody construct. In addition, the antibody binds Fcγ-receptor type I, II and/or III positive cells via an Fc-portion, or by a third antigen specificity, thereby linking engagement of accessory cells to T-cell activation and target antigen binding.
The antibody is used together with a carrier consisting of homologous virus-like particles (VLP) and/or heterologous/chimeric VLP. In the composition, the target antigen and optionally one or more further antigens are associated with or conjugated to the VLP, providing an antigen presentation format in which the target antigen is presented in isolated forms and can be part of particulate VLP-associated constructs.
The approach is described as generating both cellular and humoral immune responses, including TH1/IFN-γ biased cellular immunity and antibody responses. The background and summary material further describe the problem as the need for vaccine or immunization strategies that drive TH1/IFN-γ biased cellular and humoral immunity, and that achieve an adjuvant-like performance without external adjuvants.
Claims Coverage
The partial content includes two independent claims: a pharmaceutical composition and a kit. Across these, the claims cover three inventive features combining CD3-engaging trifunctional bispecific/trispecific antibody, Fcγ-receptor engagement, and VLP-associated antigen presentation.
CD3-activating trifunctional bispecific/trispecific antibody engaging target antigen
A trifunctional bispecific antibody and/or a trispecific antibody binding to a T cell via CD3 and activating said T cell, binding to a target antigen other than CD3, and engaging Fcγ-receptor type I, II and/or III positive cells via an Fc-portion, or by a third antigen specificity.
VLP carrier associating/conjugating target antigen and optionally further antigens
A pharmaceutically acceptable carrier selected from homologous virus-like particles (VLP) and heterologous/chimeric VLP, wherein said target antigen and optionally one or more further antigens are associated with or conjugated to the VLP.
Two-container kit combining antibody container and VLP antigen container
A kit comprising two containers, the first container containing a trifunctional bispecific and/or trispecific antibody having binding to a T cell via CD3 and activating said T cell, binding to a target antigen other than CD3, and binding to Fcγ-receptor type I, II and/or III positive cells via an Fc-portion, or by a third antigen specificity, and the second container containing a carrier selected from homologous VLP and heterologous/chimeric VLP with said target antigen and optionally one or more further antigens conjugated to or associated with the VLP.
Overall, the claim coverage centers on combining an intact trifunctional bispecific/trispecific antibody that activates CD3+ T cells while binding a non-CD3 target antigen and engaging Fcγ-receptor type I/II/III positive cells, with a homologous or heterologous/chimeric VLP carrier that associates or conjugates the target antigen and optionally additional antigens. The kit claim provides the same combination in two separate containers.
Stated Advantages
TH1/IFN-γ biased cellular and humoral immunity is generated without external adjuvants.
Adjuvant-like superiority is described over an aluminum-salt adjuvant.
Enhanced IFN-γ–producing CD8+ T-cell responses are described.
Markedly increased anti-target and/or anti-VLP antibody titers are described.
Prolonged survival after lethal CT26-EpCAM tumor challenge is described.
Documented Applications
Vaccine or immunization in mammals using a trifunctional bispecific/trispecific antibody together with VLP carrying target antigen.
Application to an EpCAM target antigen, including soluble or VLP-conjugated EpCAM with anti-EpCAM×anti-CD3 BiLu and associated immune response measurements.
Use in a lethal CT26-EpCAM tumor challenge to assess survival.
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