Background
Current second-generation CAR T cell products rely on CD28 or 4-1BB costimulatory domains, additions that respectively favor rapid cytolysis or long-term persistence, but rarely both. Preclinical modeling and retrospective analysis have lin…
Background
Antigen loss and tumor heterogeneity present significant challenges for successful immunotherapies. T-cell receptor (TCR)-based therapies rely on the recognition of epitopes derived from intracellular tumor proteins presented by major histo…
Background
The adoptive transfer of T cells engineered to express chimeric antigen receptors (CAR-T) has shown high efficacy and safety in treating various hematologic malignancies. However, many hematologic disorders, such as BCR::ABL1-negative myelo…
Background
Engineering chimeric antigen receptor (CAR) T cells with logic-gated synthetic Notch (synNotch) receptor circuits can enhance specificity and mitigate on-target/off-tumor toxicity. However, the conventional synNotch system uses two lentivir…
Background
Chimeric antigen receptor (CAR)-T cell therapy has been successful for the treatment of hematological cancers but less effective against solid tumors, a phenomenon that results from the immunosuppressive nature of the tumor microenvironment…
Background
Chimeric antigen receptor (CAR) T-cell therapies are highly efficacious for several different hematologic cancers. However, for most CAR T targets it is observed that low surface antigen density on tumors can significantly reduce therapeuti…
Background
Chimeric antigen receptor (CAR) T cells have achieved remarkable clinical success. However, up to 50% of patients with CAR T-cell treated leukemia relapse and long-term survivor data indicate that CAR T cell persistence is key to enforcing …
Background
The effectiveness of immunotherapies against glioblastoma (GB) remains limited. A major obstacle in advancing new strategies is the reliance on non-autologous systems, which do not accurately mimic the true extent of inter-patient heterogen…
Background
Adoptive transfer of T-cell receptor-engineered T cells (TCR-T cells) has shown promising efficacy in solid tumor treatment, but achieving clinical benefit typically requires infusion of tens of billions of cells. The commonly used rapid ex…
Background
High-risk neuroblastoma (HR-NBL) is an aggressive tumor of the sympathetic nervous system with high risk of relapse and poor overall survival. Allogeneic hematopoietic cell transplant (allo-HCT) has been used previously in patients with HR-…
