[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Research Letter
Association of VA Surgeons
November 2016

Pancreatic Cancer Cell Lysis by Cell-Penetrating Peptide-MAGE-A3–Induced Cytotoxic T Lymphocytes

Author Affiliations
  • 1Wayne State University School of Medicine, Detroit, Michigan
  • 2John D. Dingell VA Medical Center, Detroit, Michigan
JAMA Surg. 2016;151(11):1086-1088. doi:10.1001/jamasurg.2016.2346

In contrast to the therapeutic advances for other malignant neoplasms, the therapeutic advances for pancreatic cancer have been slow, with the 5-year survival rate currently at less than 8% for patients with pancreatic cancer.1 Immunotherapy is a particularly appealing approach to pancreatic cancer owing to its potential for eliminating tumor cells that are often unreachable by conventional therapies and its negligible side effects. Along these lines, dendritic cells (DCs) are central to the generation of effector cytotoxic CD8+ T lymphocytes (CTLs) that recognize tumor-specific antigens (TSAs) expressed on the surface of cancer cells. MAGE-A3 (melanoma antigen family A, 3) is a TSA expressed in a significant fraction of pancreatic cancers,2 thus providing an opportunity for introducing DC-based immunotherapy. However, clinically meaningful antitumor immune responses in DC vaccine trials have been sparse owing, in part, to suboptimal intracellular bioavailability of TSA to HLA class I molecules. Various cell-penetrating peptide (CPP) domains are known to ferry covalently linked heterologous TSAs across the plasma membrane into the cytosolic compartment to access HLA class I molecules.3 We and others have previously demonstrated that CPP effectively increased the intracellular entry of TSAs.4,5 We extend this work by investigating whether DCs pulsed with MAGE-A3 linked to CPP could elicit more effective antitumor CTL responses.