UNASSIGNED: DNA vaccines have demonstrated anti- @entity5 efficacy in multiple preclinical models, but low immunogenicity has been observed in several @entity1 clinical trials. This has led to many approaches seeking to improve the immunogenicity of DNA vaccines. We previously reported that a DNA vaccine encoding the cancer-testis antigen SSX2, modified to encode altered epitopes with increased MHC class I affinity, elicited a greater frequency of cytolytic, multifunctional CD8+ T cells in non- @entity5 -bearing @entity19 . In this report we sought to test if this optimized vaccine resulted in increased anti- @entity5 activity in @entity19 bearing an HLA-A2-expressing @entity5 engineered to express SSX2. We found that immunization of @entity5 -bearing @entity19 with the optimized vaccine elicited a surprisingly inferior anti- @entity5 effect relative to the native vaccine. Both native and optimized vaccines led to increased expression of @entity26327 on @entity5 cells, but antigen-specific CD8+ T cells from @entity19 immunized with the optimized construct expressed higher @entity17797 . Splenocytes from immunized animals induced @entity26327 expression on @entity5 cells in vitro. Anti- @entity5 activity of the optimized vaccine could be increased when combined with antibodies blocking @entity17797 or @entity26327 , or by targeting a @entity5 line not expressing @entity26327 . These findings suggest that vaccines aimed at eliciting effector CD8+ T cells, and DNA vaccines in particular, might best be combined with @entity17797 pathway inhibitors in clinical trials. This may be particularly advantageous for vaccines targeting @entity263 , a disease for which anti- @entity5 vaccines have demonstrated clinical benefit and yet @entity17797 pathway inhibitors alone have shown little efficacy to date.

@entity17797 or XXXX Blockade Restores Anti-Tumor Efficacy Following SSX2 Epitope-Modified DNA Vaccine Immunization.

@entity1 :: ('9606', 'Species') :: ['human'] @entity263 :: ('MESH:D011471', 'Disease') :: ['prostate cancer'] @entity17797 :: ('18566(Tax:10090)', 'Gene') :: ['PD-1'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity26327 :: ('60533(Tax:10090)', 'Gene') :: ['PD-L1'] @entity19 :: ('10090', 'Species') :: ['mice']
@entity26327 :: (60533(Tax:10090),Gene) :: ['PD-L1']
