HyperAcute® Immunotherapies

HyperAcute cancer immunotherapies are off-the-shelf products composed of a mixture of irradiated, allogeneic, whole cancer cells that have been genetically modified to add α(1,3)-Galactosyl (αGal) residues to cell-surface lipids and proteins. The αGal epitopes function as a molecular adjuvant, effectively harnessing the mechanism responsible for hyperacute rejection of xenotransplants.

HyperAcute immunotherapies are designed to break tolerance and enable longer duration of anti-tumor effect. NewLink’s HyperAcute technology yields a unique combination of advantages, including:

  • Rapid and strong onset of immune response triggered by pre-existing, naturally occurring, high-titer antibodies to αGal;
  • Complement-mediated cell lysis generating immune system "danger signals" that elicit activation and recruitment of antigen presenting cells (APCs);
  • Anti-αGal-dependent generation of multiple immune responses engaging dendritic cells, macrophages, eosinophils, and NK cells; and...
  • FcγR-mediated phagocytosis and tumor-associated antigen (TAA) uptake by APCs resulting in activation of both cytotoxic CD8+ T-cells and CD4+ helper T-cells, as well as activation and differentiation of tumor antigen-specific B-cells.

Although NewLink's technology is applicable to antigen-specific constructs, we believe allogeneic, whole cell-based vaccines represent the best approach for effective cancer immunotherapy. Whole tumor cells express diverse arrays of TAAs, thus increasing the probability of generating an immune response against shared tumor antigen present in the target tumor cells. Use of allogeneic cell lines affords substantial benefits in relation to cost-effectiveness and scalability as compared to autologous approaches, and it may also enhance immunogenicity of some TAAs in individual patients.

We have developed HyperAcute immunotherapies specific for lung cancer, pancreatic cancer, melanoma, prostate cancer, and breast cancer. To date these vaccines have been administered to over 135 patients in Phase 1 and Phase 2 trials with results clearly demonstrating safety and suggesting significant efficacy. NewLink-sponsored Phase 2 studies in lung cancer and pancreatic cancer are continuing, and the HyperAcute product for melanoma is showing early promise in a small, investigator-sponsored Phase 2 study. We plan to initiate a pivotal trial in pancreatic cancer in early 2010.