RESUMO
For successful clinical tumor immunotherapy outcomes, strong immune responses against tumor antigens must be generated. Cell-based vaccines compromise one strategy with which to induce appropriate strong immune responses. Previously, we established a natural killer T-cell (NKT) ligand-loaded, adenoviral vector-transduced B-cell-based anticancer cellular vaccine. To enhance tumor antigen delivery to B cells, we established a modified adenoviral vector (Ad-k35) that encoded a truncated form of the breast cancer antigen Her2/neu (Ad-k35HM) in which fiber structure was substituted with adenovirus serotype 35. We observed increased tumor antigen expression with Ad-k35HM in both human and murine B cells. In addition, an Ad-k35HM-transduced B-cell vaccine elicited strong antigen-specific cellular and humoral immune responses that were further enhanced with the additional loading of soluble NKT ligand KBC009. An Ad-k35HM-transduced, KBC009-loaded B-cell vaccine efficiently suppressed the in vivo growth of established tumors in a mouse model. Moreover, the vaccine elicited human leukocyte antigen (HLA)-A2 epitope-specific cytotoxic T-cell responses in B6.Cg (CB)-Tg (HLA-A/H2-D) 2Enge/Jat mice. These findings indicated that the Ad-k35 could be appropriate for the preclinical and clinical development of B-cell-based anticancer immunotherapies.
Assuntos
Linfócitos B/imunologia , Vacinas Anticâncer , Dependovirus/genética , Neoplasias Mamárias Experimentais/terapia , Receptor ErbB-2/genética , Animais , Linfócitos B/virologia , Vacinas Anticâncer/imunologia , Células Cultivadas , Dependovirus/metabolismo , Feminino , Vetores Genéticos , Antígeno HLA-A2/imunologia , Humanos , Imunoterapia , Neoplasias Mamárias Experimentais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Células T Matadoras Naturais/imunologia , Receptor ErbB-2/metabolismo , Linfócitos T Citotóxicos/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Dou Ke Jian(The Key of Smallpox) was written by Zhu Xun in the late Ming dynasty,collated and published by Zhu Fengtai in the Qing dynasty.It was rarely studied in China ,but have a far-reaching influence in Japan.By comparing with other works about smallpox and refering to the Japanese Ikeda family's Doukejian Huitong, Doukejian Siheng, Doukejian Shanzhengbuzhu completed on the basis of Dou Ke Jian,this paper systematically reviews the author's life, compilation and publication background, main content, academic characteristics and value, and influence on later generations.The views advocated in this book, such as "toxin hidden in the spleen meridians, attaching importance to qi and blood", "distinguishing between the exterior and interior, deficiency and excess, and take the lips and tongue as the key" have important reference value for the treatment of infectious diseases in later generations.