About 45,000 cases of pancreatic cancer are diagnosed every year in the US alone. It is often diagnosed late because its early symptoms are nonspecific
Pancreatic cancer is often diagnosed late because its early symptoms are nonspecific; the US National Cancer Institute estimates a mortality rate of 96%, with one-year and five-year survival rates of 24% and just 5%.
US biotech NewLink Genetics is developing algenpantucel-L, a potential add-on therapy for patients with surgically resected pancreatic cancer. The vaccine consists of two lines of irradiated allogeneic pancreatic cancer cells that have been transfected to express murine a-1,3-galactosyltransferase. On vaccination, murine a-1,3-galactosyl, or alpha-gal, carbohydrate residues are expressed on the cell membrane glycoproteins and glycolipids of the vaccine pancreatic cancer cell allograft.
The murine alpha-gal epitopes, which human cells do not have, cause an acute rejection of the allograft, as the human anti-alpha-gal antibodies that naturally occur in the gut microflora bind to the murine epitopes. This causes antibody-dependent cell-mediated cytotoxicity, or ADCC, towards the allograft cells. The body’s immune system then attacks and kills the endogenous pancreatic cancer cells because it now recognises the antigens that are shared between the endogenous and the vaccine cells.
In an open-label, single arm Phase II study, 70 resected pancreatic cancer patients were given algenpantucel-L plus the standard adjuvant therapy of gemcitabine, 5-fluorouracil and radiotherapy.1 The overall one-year disease-free survival rate was 63%, and the overall survival rate 86%. This compares favourably with historical control survival data, of 45% and 63% respectively. Those given 300M cells per dose had a higher one-year disease-free survival rate of 81% than those given 100M cells per dose at 52%. Two-thirds of patients had significant skin reactions at the injection sites, and many long-term survivors continued to experience periodic skin flares long after treatment had ceased.
A Phase III trial is now underway. A second Phase III trial, in patients with borderline resectable or locally advanced unresectable pancreatic cancer, was announced in October 2012, with patients receiving the chemotherapy combination leucovorin, 5-fluorouracil, irinotecan and oxaliplatin, with or without the vaccine.
1. J.M. Hardacre et al. J. Clin. Oncol. 2012 (suppl.), Abst. 4049