Recent advances in cellular immunotherapy for lymphoid malignancies

Chung, Haerim; Cho, Hyunsoo

doi:10.5045/br.2023.2023177

Cited by 2 publications

(2 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We are in the era of immunotherapy for B-ALL with CD19/CD3 bispecifics and CD19 CAR T cells. Despite high short-term response rates, a significant proportion of patients experience relapses, and patients with CD19-negative relapse have shown to have a poor prognosis. , However, monitoring MRD and diagnosing relapse by flow cytometry in patients with CD19-negative relapse have been challenging due to the loss of one of the target antigen. Therefore, identifying blasts in a CD19-negative population is an important issue in real-world practice.…”

Section: Discussionmentioning

confidence: 99%

3D Amplified Single-Cell RNA and Protein Imaging Identifies Oncogenic Transcript Subtypes in B-Cell Acute Lymphoblastic Leukemia

Shin,

Kim,

Yun

et al. 2024

ACS Nano

Self Cite

View full text Add to dashboard Cite

Simultaneous in situ detection of transcript and protein markers at the single-cell level is essential for gaining a better understanding of tumor heterogeneity and for predicting and monitoring treatment responses. However, the limited accessibility to advanced 3D imaging techniques has hindered their rapid implementation. Here, we present a 3D single-cell imaging technique, termed 3D digital rolling circle amplification (4DRCA), capable of the multiplexed and amplified simultaneous digital quantification of single-cell RNAs and proteins using standard fluorescence microscopy and off-the-shelf reagents. We generated spectrally distinguishable DNA amplicons from molecular markers through an integrative protocol combining single-cell RNA and protein assays and directly enumerated the amplicons by leveraging an opensource algorithm for 3D deconvolution with a custom-built automatic gating algorithm. With 4DRCA, we were able to simultaneously quantify surface protein markers and cytokine transcripts in T-lymphocytes. We also show that 4DRCA can distinguish BCR-ABL1 fusion transcript positive B-cell acute lymphoblastic leukemia cells with or without CD19 protein expression. The accessibility and extensibility of 4DRCA render it broadly applicable to other cell-based diagnostic workflows, enabling sensitive and accurate single-cell RNA and protein profiling.

show abstract

Section: Discussionmentioning

confidence: 99%

3D Amplified Single-Cell RNA and Protein Imaging Identifies Oncogenic Transcript Subtypes in B-Cell Acute Lymphoblastic Leukemia

Shin,

Kim,

Yun

et al. 2024

ACS Nano

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, our work suggests that the ability of NKG2D CAR NK cells may be impaired in the context of large tumor volume and high level of sMICA, thus testing whether this could be overcome by huB10G5 might be a beneficial synergistic strategy to improve cellular immunotherapy outcome. 74 This combination presents opportunities to improve NKG2D-dependent NK cell-mediated immunotherapy strategies providing the advantage of not only clearing sMICA but also promoting ADCC, as huB10G5 and the NKG2D receptor binds to MIC differently to allow engagement of NKG2D on NK cells against MIC-expressing cells. 38 In conclusion, we show that the MICA/B gene expressions are enriched in MM and high level of MICA expression is associated with better OS.…”

Section: Discussionmentioning

confidence: 99%

Clearing soluble MIC reverses the impaired function of natural killer cells from patients with multiple myeloma

Kim,

Chung,

Kwak

et al. 2024

J Immunother Cancer

Self Cite

View full text Add to dashboard Cite

BackgroundMajor histocompatibility complex (MHC) class I chain-related protein (MIC) is a stress-induced ligand released from multiple myeloma (MM) cells during progression, and soluble MIC impairs natural killer group 2D (NKG2D) activating receptor-mediated recognition and function of natural killer (NK) cells. However, whether clearing soluble MIC with a monoclonal antibody (mAb) can restore NK cell activity of MM patients remains undetermined.MethodsWe analyzed The Cancer Genome Atlas (TCGA) Multiple Myeloma Research Foundation (MMRF) CoMMpass data set to examine the prognostic significance ofMICexpression in MM. We examined the level of soluble MIC in paired peripheral blood (PB) and bone marrow (BM) plasma of patients with MM at diagnosis by ELISA. We evaluated the correlation between the level of soluble MIC and immunophenotype of NK cells from MM patients by multicolor flow cytometry. We also generated MIC-overexpressing MM cell line and characterized the cytotoxic function of patient NK cells in the presence of soluble MIC, and examined the impact of clearing soluble MIC with a humanized mAb (huB10G5).ResultsWe characterize the importance of MICA in MM by revealing the significantly better overall survival of patients with highMICAexpression from TCGA MMRF CoMMpass data set. The level of soluble MICA is more highly elevated in MM than in precursor stages, and the concentration of soluble MICA is higher in BM plasma than in PB. The concentration of soluble MICA in BM was correlated with myeloma burden, while it was negatively correlated with the frequency of NKG2D+NK cells in diagnostic BM aspirates of MM patients. Soluble MICA downregulated NKG2D expression and decreased cytotoxicity of MM patient NK cellsex vivo, which were reversed by a humanized soluble MIC-clearing mAb (huB10G5) with enhanced degranulation of NK cells.ConclusionsOur findings indicate targeting soluble MIC with huB10G5 might be a viable therapeutic approach to promote NKG2D-dependent cellular immunotherapy outcome in MM.

show abstract

Recent advances in cellular immunotherapy for lymphoid malignancies

Cited by 2 publications

References 66 publications

3D Amplified Single-Cell RNA and Protein Imaging Identifies Oncogenic Transcript Subtypes in B-Cell Acute Lymphoblastic Leukemia

3D Amplified Single-Cell RNA and Protein Imaging Identifies Oncogenic Transcript Subtypes in B-Cell Acute Lymphoblastic Leukemia

Clearing soluble MIC reverses the impaired function of natural killer cells from patients with multiple myeloma

Contact Info

Product

Resources

About