Anti-BST2 (C-terminal) polyclonal antibody

A murine (mAHM) and a humanized (AHM) monoclonal antibody against CD317 (also called tetherin, BST2, or HM1.24 antigen), expressed preferentially in neoplastic B cells such as multiple myeloma, exhibited antitumor effects as a result of antibody-dependent cellular cytotoxicity (ADCC). The putative interferon (IFN) response elements IRF-1/2 and ISGF3 are present in the promoter of the CD317 gene, and IFN has been used for the treatment of not only myeloproliferative diseases but also solid tumors such as renal cell carcinoma (RCC) and melanoma. Therefore, we examined the effects of IFN on the expression of CD317 and on the antitumor activity of AHM and mAHM in RCC and melanoma. Flow cytometry and in vitro ADCC assays with human or mouse effector cells demonstrated that IFN-alpha markedly increased the amount of cell surface CD317 and augmented the ADCC activity of mAHM and AHM in RCC cells and to a lesser extent in melanoma cells. Administration of IFN-alpha to mice bearing RCC xenografts also increased the expression of CD317 in tumor cells. When coadministered with IFN-alpha, mAHM exhibited more profound antitumor activity in both IFN-alpha-sensitive and -insensitive RCC xenograft models. Thus, AHM in combination with IFN-alpha may be an effective therapy for the treatment of RCC. (Cancer Sci 2008; 99: 2461-2466).

Human memory and naive CD4 T cells can mainly be identified by the reciprocal expression of the CD45RO or CD45RA isoforms. In HIV-1 infection, blood CD45RO memory CD4 T cells are preferentially infected and serve as a major viral reservoir. The molecular mechanism dictating this differential susceptibility to HIV-1 remains largely obscure. Here, we report that the different susceptibility of memory and naive T cells to HIV is not determined by restriction factors such as Apobec3G or BST2. However, we observed a phenotypic distinction between human CD45RO and CD45RA resting CD4 T cells in their cortical actin density and actin dynamics. CD45RO CD4 T cells possess a higher cortical actin density and can be distinguished as CD45RO(+)Actin(high). In contrast, CD45RA T cells are phenotypically CD45RA(+)Actin(low). In addition, the cortical actin in CD45RO memory CD4 T cells is more dynamic and can respond to low dosages of chemotactic induction by SDF-1, whereas that of naive cells cannot, despite a similar level of the chemokine receptor CXCR4 present on both cells. We further demonstrate that this difference in the cortical actin contributes to their differential susceptibility to HIV-1; resting memory but not naive T cells are highly responsive to HIV-mediated actin dynamics that promote higher levels of viral entry and early DNA synthesis in resting memory CD4 T cells. Furthermore, transient induction of actin dynamics in resting naive T cells rescues HIV latent infection following CD3/CD28 stimulation. These results suggest a key role of chemotactic actin activity in facilitating HIV-1 latent infection of these T cell subsets.