JCI online early table of contents: April 8, 2008

ONCOLOGY

Anticancer agents targeted specifically to tumors

Much effort is being invested in trying to target anticancer therapies more specifically to tumors to decrease harmful side effects. In a new study, Ruth Ganss and colleagues, at the Western Australian Institute for Medical Research, Perth, have used a tumor-homing peptide to engineer two immunotherapeutic anticancer agents, an anti-CD40 antibody and IL-2, such that they selectively targeted spontaneously arising tumors in a transgenic mouse model of cancer of the pancreatic islet cells.

When the engineered agents were injected intravenously, either together or separately, into tumor-bearing mice they were found to accumulate in blood vessels in the tumors. Together, these agents affected the endothelial cells lining the tumor blood vessels, reducing the number of blood vessels and thereby substantially delaying tumor growth. Treating tumor-bearing mice with a combination of the tumor-targeted agents and infusions of preactivated antitumor immune cells led to long-term disease-free survival. The authors believe that this combination was highly effective because the tumor-targeted anti-CD40 antibody modified the endothelial cells lining the tumor blood vessels such that the infused preactivated antitumor immune cells were able to accumulate in the tumor and that the tumor-targeted IL-2 helped the accumulated immune cells persist.

TITLE: Vascular targeting of anti-CD40 antibodies and IL-2 into autochthonous tumors enhances immunotherapy in mice

AUTHOR CONTACT:

Ruth Ganss

Western Australian Institute for Medical Research, Perth, Western Australia, Australia.

Phone: 61-8-9224-0354; Fax: 61-8-9224-0322; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33201

ONCOLOGY

Understanding why an attack on two fronts has anticancer effects

One mechanism by which a combination therapy that was previously shown to be efficient at clearing tumors in a mouse model of cancer has now been elucidated by Peter Kim and colleagues, at Johns Hopkins University School of Medicine, Baltimore.

Neu-N mice develop spontaneous breast cancer and vaccination with a HER-2/neu–expressing, GM-CSF–secreting whole cell vaccine induces ineffective antitumor immune responses. However, if the vaccination is combined with treatment with a neu-specific antibody, the efficient antitumor response enables mice to remain tumor-free and even eradicates transplanted neu-expressing tumors. In this study, the combination therapy was shown to markedly improve the CD8+ T cell antitumor immune response by enhancing Fc-mediated activation of the immune cells that initiate the CD8+ T cell antitumor immune response. The authors therefore suggest that combination therapies that mount a multifaceted attack on the same tumor protein (in this case neu) might be useful for inducing effective antitumor immune responses targeted to other tumor proteins.

TITLE: Antibody association with HER-2/neu-targeted vaccine enhances CD8+ T cell responses in mice through Fc-mediated activation of DCs

AUTHOR CONTACT:

Peter S. Kim