Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma.

Recombinant interleukin-2 (rIL-2) is a pleiotropic cytokine that activates select immune effector cell responses associated with antitumor activity, including antibody-dependent cellular cytotoxicity (ADCC). Rituximab is an anti-CD20 monoclonal antibody that activates ADCC in non-Hodgkin lymphoma (NHL). The ability of rIL-2 to augment rituximab-dependent tumor responses was investigated.

Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity.

ONYX-015 is an adenovirus that lacks the E1B-55K gene product for p53 degradation. Thus, ONYX-015 was conceived as an oncolytic virus that would selectively replicate in p53-defective tumor cells. Here we show that loss of E1B-55K leads to the induction, but not the activation, of p53 in ONYX-015-infected primary cells.

Selectively replicating adenoviruses targeting deregulated E2F activity are potent, systemic antitumor agents.

We have engineered a human adenovirus, ONYX-411, that selectively replicates in human tumor cells, but not normal cells, depending upon the status of their retinoblastoma tumor suppressor protein (pRB) pathway. Early and late viral gene expression as well as DNA replication were significantly reduced in a functional pRB-pathway-dependent manner, resulting in a restricted replication profile similar to that of nonreplicating adenoviruses in normal cells both in vitro and in vivo. In contrast, the viral life cycle and tumor cell killing activity of ONYX-411 was comparable to that of wild-type adenovirus following infection of human tumor cells in vitro as well as after systemic administration in tumor-bearing animals.