SLAMF7 (SLAM Family Member 7)

Tyrosine-kinase inhibitor dasatinib rapidly and reversibly inhibited CAR-T activation, serving as an efficient "on/off" switch with the limitation of also inhibiting unmodified T cells...However, conditioning with fludarabine/cyclophosphamide profoundly depletes NK cells, limiting antibody-dependent CAR-T clearance in patients...In this work, we demonstrate that the BCMA-targeting ADC belantamab-mafodotin selectively eliminates BCMA co-expressing CAR-T cells without affecting unmodified T cells. These findings suggest ADCs as a potent, effector cell-independent safety mechanism for CAR-T therapies, potentially enhancing controllability and safety in future clinical applications.

ADCC was assessed by flow cytometry using E (100 μg/mL), rituximab (R, 100 μg/mL), and their combination (E + R). The combination of E + R showed no significant synergy over monotherapies. In conclusion, elotuzumab induced significant ADCC in CLL cells, warranting further therapeutic evaluation.

CD320, SLC44A1, and TNFRSF13B are promising, clinically relevant targets for CAR T-cell therapy in MM. Their stage-specific expression and prognostic significance support their potential to enhance existing immunotherapeutic strategies.

Conversely, therapeutic co-engagement of SLAMF7 via recombinant SLAMF7 (rm-SLAMF7) plus PD-1 blockade significantly amplified anti-tumor responses, characterized by enhanced T cell expansion, activation, and cytotoxic potential. Consequently, these outcomes suggested that targeting SLAMF7 may offer a strategy to enhance PD-1-directed immunotherapy in NSCLC.

GSDME functions as a tumor suppressor by enhancing radiosensitivity and inhibiting proliferation and migration in ESCC, through the suppression of the NF-κB signaling pathway. These findings nominate GSDME as a promising biomarker and the NF-κB signaling pathway as a therapeutic target for overcoming radioresistance in ESCC.

Ide-cel and Cilta-cel are CAR-T cells directed against BCMA, having received FDA approval for RRMM based on the Phase 2 KarMMa and CARTITUDE trials, respectively...Additional anti-BCMA targeted medicines, including LCAR-B38M, completely humanized CAR-T (FHVH-T), P-BCMA-ALLO-1, ALLO-715, and anti-BCMA CAR-NK, provide promising treatment options. Moreover, the anti-CD19 Fast-CAR, designed to shorten production time, and PHE885, which possesses in-vivo proliferation capability, are regarded as very efficacious...The development of academic CAR-Ts such as ARI0002h, HBI0101, eque-cel, zevor-cel, anito-cel, and Sleeping Beauty (utilizing a non-viral vector) have importance due to their accessibility and cost-effectiveness...To overcome these issues, strategies are being implemented, including combination therapy, the incorporation of gamma-secretase inhibitors etc. In conclusion, CAR-T treatments have evolved into an effective therapy modality being anticipated to be utilized in earlier phases in the future. Gene editing (CRISPR) method contributes to the future perspective.

Use of alternate plasma-cell gating markers beyond the conventional backbone can be critical even in upfront diagnostic settings. Incorporating multiple, non-overlapping plasma-cell markers-including antibodies designed to avoid therapeutic masking-improves plasma-cell detection in both MRD assessment and initial diagnostic flow cytometry panels.

Although lenalidomide/bortezomib/dexamethasone (RVd) and cyclophosphamide/bortezomib/dexamethasone (CyBorD) are clinically effective, their precise impacts on PC/B-cell maturation remain unclear. RVd responders further downregulated CD56, CD269, and CD329, and increased CD243. These shared and divergent modulations elucidate the molecular underpinnings of RVd and CyBorD efficacy and inform precision regimen selection.

In this Review, we examine the evidence supporting phagocytic checkpoints as targets for cancer therapy, while highlighting current challenges associated with this therapeutic strategy. We also offer recommendations for enhancing the efficacy and safety of this approach in future work.

Comparative transcriptomic analysis revealed distinct gene expression profiles between CD4+GPR56+ and CD4+GPR56- T cells, with enriched pathways related to immune activation and cytotoxicity. Together, our results identify GPR56 as a novel and functionally significant surface marker for CD4+ CTLs, providing new insights into their role in autoimmune disorders and their potential for targeted therapeutic strategies.

In metastatic urothelial cancer, scPER predicted TGFβ-mediated inhibition of CD4 naïve T cells to diminish PD-L1 checkpoint blockade efficacy. scPER enables robust integration of scRNA-seq datasets to estimate cellular proportions across tumors and identify clinically relevant cell populations.

Emerging clinical data suggest that CAR-NK cell therapy may combine the specificity of CAR recognition with the inherent safety and versatility of NK biology, offering a potential paradigm shift in the treatment of relapsed or refractory MM. Further clinical validation will determine whether CAR-NK cell therapy can achieve durable remission and complement or surpass current CAR-T modalities.