Dysregulated expression of the tumor suppressor p14ARF in cancer provides an effective target for TCR-T cell therapeutics

Background
The CDKN2A gene encodes two canonical tumor suppressors, p16INK4A and p14ARF, which safeguard cells from malignant transformation by inducing cell cycle arrest and apoptosis in response to aberrant growth signals. Paradoxically, many cancer…

MMP3 overexpression enhances CAR-T cell infiltration and antitumor activity in a CAF-enriched solid tumor model

Background
Chimeric antigen receptor (CAR) T cell therapy has shown remarkable success in hematologic malignancies but faces substantial challenges in solid tumors. One of the main obstacles is the extracellular matrix (ECM), which serves as the physi…

CD2 costimulation bridges potent CAR-induced cytolysis and durable persistence

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…

Trispecific targeting of T cells engineered with TCR mimic antibodies to limit antigen escape

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…

Mutant calreticulin enables potent and selective CAR-T cell therapy in preclinical models of myeloproliferative neoplasms

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…

Engineering single-vector logic-gated CAR T cells with transgene sizes beyond current limitations

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…

Chimeric antigen receptor dendritic cells suppress melanoma growth in preclinical cancer models

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…

Affinity-matured CD72-targeting nanobody CAR T cells enhance elimination of antigen-low B-cell malignancies

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…

AMPK agonism optimizes the in vivo activation and antileukemic efficacy of chimeric antigen receptor T cells

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 …

Autologous profiling reveals inter-patient heterogeneity in V{delta}2+{gamma}{delta}TIL responses to glioblastoma driven by extracellular matrix-BTN3A axis

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…

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