Ongoing Projects in Dr. Ragupathi’s Laboratory

  • Stability and related FDA-required quality control testing is ongoing for the vaccines currently in multi-center Phase II trials.
  • Collaborating with chemist Samuel Danishefsky, we are testing a series of unimolecular polyvalent antigen constructs. A clinical trial with the initial unimolecular polyvalent construct is ongoing in ovarian cancer patients. Investigations into class, subclass, and functional characteristics of polyvalent vaccine-induced antibodies, as well as the correlation of these responses to clinical outcome, are under way.
  • We are evaluating a series of fully human monoclonal antibodies derived from our vaccinated patients to define their CDC and ADCC activities in vitro, and the ability of these antibodies to protect from tumor challenge in vivo in xenograft models.
  • We are also exploring approaches to further increase the efficacy of vaccine-induced antibodies and administered monoclonal antibodies in these murine models, focusing on combinations with chemotherapy — especially with inhibitors of the PI3K pathway.
  • We are testing the impact of selected synthetic QS-21 analogues on immune responses to a range of carbohydrate and peptide antigens targeting cancer as well as malaria, Lyme disease,  and other infectious diseases.
  • Since the mechanism of action of QS-21 and the analogues is largely unknown, we are collaborating with Jason Lewis and Derek Tan to utilize semi-synthetic labeled QS-21 analogues synthesized with labels to understand the biodistribution and mechanism of action of QS-21, and how different portions of the QS-21 molecule contribute to adjuvant activity and toxicity.