A new cancer vaccine consists of dendritic cells transduced with a full-length double mutant survivin gene delivered via an adenoviral vector. The vaccine will target survivin-expressing tumors. The survivin protein is crucial for cancer cell function and is expressed in over 50% of patients in twelve distinct types of cancer. In Phase 1 clinical trial, multiple myeloma patients were given this variant survivin vaccine prior to and post autologous stem cell transplantation with 4 out of 13 patients (31%) achieving a complete response (CR). Historical rates are expected to be closer to 17%. Patients with CRs have better survival outcomes years later.
- Survivin was designated a Top 25 tumor-associated (TAA) antigen by the NCI based on immunogenicity and differential expression in 50-80% of patients with more than 12 distinct cancer types. Survivin plays an essential role as an inhibitor of cancer cell death and promotes growth, metastasis, and treatment resistance of malignant cells.
- Multiple myeloma (MM) is an incurable cancer with an estimated 30,280 cases in the US in 2017. Over 40% of MM samples overexpress survivin and have significantly reduced T-cell responses against survivin protein. Approximately 5,000 MM patients receive high-dose chemotherapy and adoptive stem cell transplant (ASCT) each year in North America. Extensive clinical studies find that patients achieving CR post-transplant have significantly higher long-term overall survival (OS) and progression-free survival (PFS) at 12-15 years.
- The survivin vaccine market is attractive, as evidenced by two products in ongoing clinical trials. First, SurVaxM, a synthetic peptide vaccine (SurVaxM) produced by MimiVax LLC, is currently in Phase I/II trials for multiple myeloma, glioblastoma, and auto-immune diseases. Recent Phase 2 data for SurVaxM in glioblastoma suggest patients may live longer with 91% survival at 12 months (n=55) compared to 60-65% for historical controls. Second, DPX-Survivac, a survivin-based peptide antigen produced by Immunovaccine Inc., is in Phase 2 trials for ovarian cancer and lymphoma. In contrast to SurVaxM and DPX- urvivac, the Moffitt full length variant survivin protein vaccine DC:AdmS should enable the presentation of multiple peptide epitopes, and recognition by a more diverse immune repertoire in patient populations.