DNA vaccines to target the cancer testis antigen PASD1 in human multiple myeloma

Leukemia. 2010 Nov;24(11):1951-9. doi: 10.1038/leu.2010.196. Epub 2010 Sep 23.


We previously described PASD1 as a new cancer testis antigen in multiple myeloma (MM) that is retained post-therapy, suggesting the use of vaccination strategies to induce anti-PASD1 immunity in a setting of minimal residual disease. We have focused on DNA fusion gene vaccines, coupling fragment C domain (DOM) of tetanus toxin with PASD1 sequence, and examined efficacy in Human Leukocyte Antigen (HLA)-A2 (HHD) transgenic mice using a human MM cell line expressing PASD1 protein and chimeric HLA-A2 class I molecules as target. DNA vaccines encoded two HLA-A2-restricted epitopes (p.DOM-PASD1(1), p.DOM-PASD1(2)) and full-length PASD1 (p.DOM-PASD1FL). p.DOM-PASD1(1) proved superior to p.DOM-PASD1(2) in generating T-cell responses in HHD mice, able to lyse the chimeric murine RMA-HHD cells. Boosting by electroporation significantly enhanced p.DOM-PASD1(1). Only p.DOM-PASD1(1) induced cytotoxic T-lymphocytes (CTLs) were able to lyse human MM target cells expressing endogenous antigen. The p.DOM-PASD1FL vaccine predominantly induced strong PASD1(1) over PASD1(2) T-cell immune responses, indicative of immunodominance. Importantly, p.DOM-PASD1FL generated immune-mediating killing of native chimeric MM cells, in the absence of exogenous added peptide, implicating PASD1(1) specific CTLs. These data demonstrate that PASD1-derived epitopes are both efficiently and selectively processed and presented by native human MM cells. Notably, they permit the use of PASD1-encoding DNA vaccine therapy in a clinical setting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / pharmacology
  • Antigens, Nuclear / genetics*
  • Antigens, Nuclear / immunology*
  • Antigens, Nuclear / pharmacology
  • Epitopes / immunology
  • HLA-A Antigens / immunology
  • HLA-A2 Antigen / immunology
  • Humans
  • Lymphoma / immunology
  • Mice
  • Mice, Transgenic
  • Multiple Myeloma / immunology*
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, DNA / immunology
  • Vaccines, DNA / therapeutic use*


  • Antigens, Neoplasm
  • Antigens, Nuclear
  • Epitopes
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • PASD1 protein, human
  • Recombinant Fusion Proteins
  • Vaccines, DNA