Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0026764 (
multiple myeloma
)
36,148
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:DNA vaccines to target the cancer testis antigen PASD1 in human multiple myeloma. 2086 11
