High-dose chemotherapy and autologous stem cell transplantation (ASCT) provides myeloma patients with the best opportunity for complete remission and long-term survival. However, relapses are common and the likelihood of cure is probably no better than 10%. Adoptive transfer of in-vivo vaccine-primed and ex-vivo costimulated autologous T-cells early after autotransplantation for myeloma followed by booster immunizations augments T-cell recovery and restoration of vaccine-specific T-cell and B-cell responses. The hypothesis behind the current project is that combination immunotherapy using a putative tumor vaccine and infusions of vaccine-primed and ex-vivo costimulated T-cells may generate anti-tumor immune responses in the post-transplant setting. The tumor vaccine for this study will be a multi-peptide vaccine containing HLA-A2 restricted epitopes from hTERT (catalytic subunit of human telomerase) and survivin (anti-apoptotic protein) - which are widely expressed in myeloma cells. The long-term objective is to develop a strategy for inducing clinically meaningful anti-myeloma immune responses in the post-autotransplant setting which can delay or prevent relapses.
Specific Aims AIM 1: To conduct a trial in which HLA A2+ patients who are autografted for myeloma receive a multi-peptide vaccine containing HLA A2 - restricted peptides from hTERT and survivin plus vaccine-primed and ex-vivo costimulated T-cells and to evaluate the safety of this combined approach in comparison to an HLA A2 negative cohort of patients who receive costimulated T- cells and a pneumococcal conjugate (PCV) control vaccine (PCV) only.
AIM 2 : To assay for development of cellular immune responses to the hTERT multi-peptide vaccine in the cohort of HLA A2+ patients who receive the combination of the multi-peptide vaccine and the vaccine-primed and costimulated T-cells. ? ? ?
| Stadtmauer, Edward A; Vogl, Dan T; Luning Prak, Eline et al. (2011) Transfer of influenza vaccine-primed costimulated autologous T cells after stem cell transplantation for multiple myeloma leads to reconstitution of influenza immunity: results of a randomized clinical trial. Blood 117:63-71 |
| Rapoport, Aaron P; Aqui, Nicole A; Stadtmauer, Edward A et al. (2011) Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma. Blood 117:788-97 |
| Rapoport, Aaron P; Stadtmauer, Edward A; Aqui, Nicole et al. (2009) Rapid immune recovery and graft-versus-host disease-like engraftment syndrome following adoptive transfer of Costimulated autologous T cells. Clin Cancer Res 15:4499-507 |
