Abstract
BackgroundGenetically engineered virus-specific T cells (VSTs) are a platform for adoptive cell therapy after allogeneic hematopoietic stem cell transplantation. However, redirection to a tumor-associated antigen by the introduction of a...
Highlights
Malignant relapse and viral infections are the two major causes for treatment failure and morbidity in patients after allogeneic hematopoietic stem cell transplantation (HSCT).[1]
Anti-tumor function predominated consistently,[10 11] or reactivities shifted between compartments depending on the type of antigen encountered.[11]. These effects are most likely explained by competition for T-cell receptor (TCR)/CD3/CD8 complex signaling components used by both the endogenous anti-v iral and introduced transgenic TCRs, as well as TCR mis-p airing between introduced and endogenous TCR chains,[11,12,13] and imply two important points: (i) the clinical benefit from controlling viral reactivation post transplant may be jeopardized when using TCR+ virus-specific T cells (VSTs), and (ii) the capacity of TCR+ VSTs to re-expand in vivo upon viral reactivation or vaccination may be limited compared to chimeric antigen receptor (CAR)+ VSTs
In TCR8+ CD4+ VSTs, both the TN and the TCM compartments were better preserved compared with NT CD4+ VSTs or TCR+ CD4+ VSTs
Summary
Malignant relapse and viral infections are the two major causes for treatment failure and morbidity in patients after allogeneic hematopoietic stem cell transplantation (HSCT).[1]. Redirection to a tumor-associated antigen by the introduction of a transgenic T-cell receptor (TCR) reduces anti-viral activity, thereby impeding the possibility of preventing or treating two distinct complications— malignant relapse and viral infection—with a single cell therapy product. Results Both transgenic CD8αβ alone and TCR8 had significant impact on the anti-viral function of engineered VSTs, and TCR8+ VSTs had comparable anti-viral activity as non-engineered VSTs as determined by IFN-γ ELISpot, ICS and cytotoxicity assays. Our approach may provide clinical benefit in preventing and treating viral infections and malignant relapse post-transplant
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