BACKGROUND: The FDA recently approved an anti-CTLA-4 antibody (Iplimumab) for the treatment of metastatic melanoma.
This decision was based on Phase III results, which demonstrate that blocking this immune checkpoint provides a survival advantage in patients with advanced disease. As a single agent, ipilimumab is also being clinically evaluated in advanced (metastatic, castrate-resistant) prostate cancer and two randomized, placebo-controlled Phase III studies have recently completed accrual.
METHODS: We used a well-described genetically engineered mouse (GEM), autochronous prostate cancer model (Pro-TRAMP) to explore the relative sequencing and dosing of anti-CTLA-4 antibody when combined with a cell-based, GM-CSF-secreting vaccine (GVAX).
RESULTS: Our results show that combined treatment results in a dramatic increase in effector CD8 T cells in the prostate gland, and enhanced tumor-antigen directed lytic function. These effects are maximized when CTLA-4 blockade is applied after, but not before, vaccination. Additional experiments, using models of metastatic disease, show that incorporation of low-dose cyclophosphamide into this combined treatment regimen results in an additional pre-clinical benefit.
CONCLUSIONS: Together these studies define a combination regimen using anti-CTLA-4 / GVAX immunotherapy and low-dose chemotherapy for potential translation to a clinical trial setting.
Written by:
Wada S, Jackson CM, Yoshimura K, Yen HR, Getnet D, Harris TJ, Goldberg MV, Bruno TC, Grosso JF, Durham N, Netto GJ, Pardoll DM, Drake CG. Are you the author?
Reference: J Transl Med. 2013 Apr 4;11(1):89.
doi: 10.1186/1479-5876-11-89
PubMed Abstract
PMID: 23557194
