Apoptosis

Identification of BARD1 as mediator between proapoptotic stress and p53-dependent apoptosis Irminger-Finger, I. et al. Mol. Cell. 8, 1255–1266 (2001) [PubMed]

We know remarkably little about the function of BRCA1, but even less about its binding partner BARD1. This study indicates that BARD1 has a dual mode of action: in the presence of BRCA1, BARD1 acts as BRCA1's accomplice in DNA repair, but the authors find that it can also act independently of BRCA1 to elevate levels of p53 and promote apoptosis. The ratio of BRCA1 to BARD1 might therefore be involved in life or death decisions.

Tumour suppressors

Activation of retinoblastoma in mammary gland leads to ductal growth suppression, differentiation, and adenocarcinoma. Jiang, Z. & Zacksenhaus, E. J. Cell Biol. 156, 185–198 (2002) [PubMed]

Although retinoblastoma is a tumour suppressor, its activation might also promote tumorigenesis because it suppresses apoptosis. Transgenic mice that expressed constitutively active Rb in the mammary gland showed reduced cell proliferation, premature differentiation and increased survival of epithelial cells. About 30% of these mice developed hyperplastic nodules, and ∼7% developed mammary adenocarcinomas. Given these results, the development of anticancer therapies that involve activating Rb should be reconsidered.

Immunotherapy

Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by artificial APCs expressing ligands for the T cell receptor, CD28 and 4‐1BB. Maus, M. V. et al. Nature Biotechnol. 20, 149–154 (2002)

One approach used to create cancer vaccines involves ex vivo priming and expansion of human cytotoxic T cells. To overcome the difficulty in obtaining sufficient numbers of these cells, the authors developed artificial antigen-presenting cells (APCs) that express ligands for the T-cell receptor and co-stimulatory surface molecules. These APCs activate and rapidly expand polyclonal or antigen-specific CD8+ T cells. The starting repertoire of CD8+ T cells was preserved during culture, and T-cell apoptosis was diminished.

Gene therapy

Chromosomal effects of adeno-associated virus vector integration. Miller, D. G. et al. Nature Genetics. 30, 147–148 (2002) [PubMed].

Adeno-associated viruses (AAVs) are currently in development as a delivery mechanism for gene therapy. But could integration of these viruses within host-cell DNA have a deleterious effect? Miller et al. now show that AAVs integrate at chromosome breaks — probably by a non-homologous end-joining pathway — and are often associated with deletions and chromosomal rearrangements, but it remains to be determined whether AAV actually causes these breaks.