摘要:
An immunogenic composition comprising a recombinant protein comprising a Bordetella CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen is provided as a cancer treatment. Methods of treatment with this immunogenic composition are also provided. In an embodiment, the therapeutic composition is a treatment for melanoma, and comprises epitopes from the HLA*0201 epitope. These epitopes include Tyr or GnT-V, and are present in the recombinant proteins CyaA-E5-Tyr and CyaA-E5-GnT-V.
摘要:
Diagnostic testing and immunomonitoring that uses genetically detoxified Bordetella pertussis CyaA as a delivery system are effective in tracking any immune responses, such as those generated by infectious and non-infectious diseases, or vaccinations, for example. T cells previously stimulated by a given antigen can be restimulated in vitro by the same antigen fused or chemically coupled to CyaA or a fragment thereof. The invention includes diagnostic tests and immunomonitoring for tuberculosis by providing a delivery system, which can deliver the M. tuberculosis immunodominant proteins ESAT-6 and CFP-10, to human cells and non-human animal cells, such as cattle. In addition, fusion proteins between CyaA and cancer antigens are also provided as diagnostic tests and immunomonitoring systems for cancers, such as melanoma.
摘要:
The invention relates to modified Bordetella adenylate cyclase toxins which are deficient for CD11b/CD18 binding and to their use in the preparation of pharmaceutical composition for the treatment of whooping cough and/or for the protection against Bordetella infection. The invention also relates to specific fragments of Bordetella adenylate cyclase comprising the CD11b/CD18 interaction domain and their use, especially for targeting a molecule of interest to CD11b expressing cells.
摘要:
A carbohydrate peptide conjugate containing: (i) a carrier containing a dendrimeric poly-lysine enabling multiple epitopes to be covalently attached thereto, (ii) at least one peptide containing one T epitope or several identical or different T-epitopes, (iii) at least one carbohydrate moiety which is tumor antigen, or a derivative thereof, containing a B epitope, provided it is not a sialoside, or several identical or different epitopes, wherein said conjugate containing at least 3-lysines and up to 15 lysine covalently linked to one another, and wherein: (a) to the NH2 and of at least two lysine residues is bound at least one carbohydrate residue being not a sialoside, optionally substituted and containing an epitope and wherein the peptide containing one T epitope is covalently bound to the end of said carbohydrate which induces immune responses.
摘要:
The invention concerns the use, in the induction of an immune response, of a synthetic microparticle polymer carrying on the surface one or more covalently bonded proteins capable of carrying one or more epitopes, the molecular weight of the protein(s) on the surface of the microparticles, being adjusted so as to direct the immune response to the induction of a humoral and cellular response or to the induction of a mainly cellular response, said microparticles have an average diameter of approximately 0.25 to 1.5 .mu.m.
摘要:
A recombinant plasmid comprises the cyaC and the cyaA genes of Bordetella which directs the expression of Bordetella, adenylate cyclase in a transformed host cell. A recombinant DNA molecule can comprise the Bordetella cyaA gene containing at least one insertion of a heterologous DNA sequence at at least one permissive site. In addition, a recombinant Bordetella adenylate cyclase comprises a heterologous epitope at a permissive site. Methods of inducing a specific B cell, helper T cell, and CTL cell immune response are provided.
摘要:
An immunogenic composition comprising a recombinant protein comprising a Bordetella CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen is provided as a cancer treatment. Methods of treatment with this immunogenic composition are also provided. In an embodiment, the therapeutic composition is a treatment for melanoma, and comprises epitopes from the HLA*0201 epitope. These epitopes include Tyr or GnT-V, and are present in the recombinant proteins CyaA-E5-Tyr and CyaA-E5-GnT-V.
摘要:
A polypeptide comprises a mutated Bordetella pertussis CyaA (SEQ ID NO:1), Bordetella parapertussis CyaA (SEQ ID NO:7), Bordetella hinzii CyaA (SEQ ID NO:8), or Bordetella bronchiseptica CyaA (SEQ ID NO:9), or a fragment thereof lacking all or part of the N-terminal catalytic domain of the CyaA, or a polypeptide having at least 95% sequence identity with SEQ ID NOS: 1, 7, 8, or 9. The glutamic acid residue at position 570 of SEQ ID NO: 1, 7, 8 or at position 569 of SEQ ID NO:9 has been substituted by a conservative amino acid residue. The lysine residue at position 860 of SEQ ID NO: 1, 7, 8 or at position 859 of SEQ ID NO:9 has been substituted by a conservative amino acid residue. The polypeptide retains the binding activity of native CyaA to CD11b expressing cell, and has a pore-forming activity which is reduced or suppressed as compared to that of the native CyaA toxin.
摘要翻译:多肽包括突变型百日咳杆菌CyaA(SEQ ID NO:1),百日咳杆菌CyaA(SEQ ID NO:7),Bordetella hinzii CyaA(SEQ ID NO:8)或支气管炎博德特氏菌CyaA(SEQ ID NO:9), 或其缺少CyaA的全部或部分N末端催化结构域的片段,或与SEQ ID NO:1,7,8或9具有至少95%序列同一性的多肽。570位的谷氨酸残基 的SEQ ID NO:1,7,8或SEQ ID NO:9的位置569已被保守的氨基酸残基取代。 SEQ ID NO:1,7,8或SEQ ID NO:9的859位的860位的赖氨酸残基被保守的氨基酸残基取代。 多肽保留天然CyaA与表达CD11b的细胞的结合活性,并且与天然CyaA毒素相比具有减少或抑制的成孔活性。
摘要:
The invention relates to a kit of parts, suitable for use in a therapy of cancer, wherein said kit comprises:(i) a recombinant protein comprising one or several polypeptides bearing one or several epitopes of one or several tumor-associated antigens, said polypeptides being inserted in the same or different permissive sites of an adenylate cyclase (CyaA) protein or of a fragment thereof, wherein said CyaA fragment retains the property of said adenylate cyclase protein to target Antigen Presenting Cells or a mixture of such recombinant proteins wherein at least one of said epitopes, or tumor associated antigens, or insertion sites of CyaA protein, or fragment of said CyaA protein is different between the various recombinant proteins in the mixture; and said kit of parts further comprises at least one of the following compounds; (ii) an agent, suitable for modulating a regulatory immune response in a patient ad optionally; (iii) an adjuvant component suitable for activating the innate immune response in a patient.
摘要:
An immunogenic composition comprising a recombinant protein comprising a Bordetella CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen is provided as a cancer treatment. Methods of treatment with this immunogenic composition are also provided. In an embodiment, the therapeutic composition is a treatment for melanoma, and comprises epitopes from the HLA*0201 epitope. These epitopes include Tyr or GnT-V, and are present in the recombinant proteins CyaA-E5-Tyr and CyaA-E5-GnT-V.