Globo h and related anti-cancer vaccines with novel...

A - Human Necessities – 61 – K

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A61K 39/00 (2006.01) A61K 39/385 (2006.01)

Patent

CA 2728341

Immunogenic compositions, cancer vaccines and methods for treating cancer are provided. Compositions compris-ing: (a) a glycan such as Globo H or an immunogenic fragment thereof, wherein the glycan is conjugated with a carrier protein by a linker such as para-nitrophenyl; and (b) an adjuvant comprising glycolipid capable of binding CDId on a dendritic cell, such as an a-galactosyl-ceramide derivative, wherein the immunogenic composition induces an immune response that induces a higher relative level of IgG isotype antibodies as compared to IgM isotype antibodies, are provided. Immunogenic compositions compris-ing the carrier protein diphtheria toxin cross-reacting material 197 (DT-CRM 197) and the adjuvant C34 are provided. Antibodies generated by immunogenic compositions disclosed herein further neutralize at least one of the antigens Globo H, stage-specific embryonic antigen-3 (SSEA-3) and stage-specific embryonic antigen-4 (SSEA-4). Therapeutics against breast cancer stem cells comprising immunogenic compositions comprising Globo H, SSEA-3 or SSEA-4 conjugated with DT-CRM 197.

La présente invention concerne des compositions immunogènes, des vaccins contre le cancer et des méthodes de traitement du cancer. Les compositions comprennent : (a) un glycane tel que Globo H ou un fragment immunogène de celui-ci, le glycane étant conjugué avec un vecteur protéique par un lieur tel que le paranitrophényle; et (b) un adjuvant comprenant un glycolipide pouvant se lier à CDId sur une cellule dendritique, tel quun dérivé da-galactosyl-céramide, la composition immunogène induisant une réponse immunitaire qui induit un niveau relatif plus élevé danticorps disotype IgG par rapport aux anticorps disotypes IgM. Linvention concerne également les compositions immunogènes comprenant le vecteur protéique DT-CRM 197 (matériau présentant une réaction croisée de la toxine diphtérique 197) et ladjuvant C34. Des anticorps générés par les compositions immunogènes décrites dans la description neutralisent ensuite au moins un des antigènes Globo H, antigène-3 embryonnaire spécifique dun stade (SSEA-3) et antigène-4 embryonnaire spécifique dun stade (SSEA-4). Linvention concerne également des agents thérapeutiques contre les cellules souches du cancer du sein comprenant des compositions immunogènes comprenant Globo H, SSEA-3 ou SSEA-4 conjugués avec DT-CRM 197.

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