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BIOMARKER:

B2M elevation

i
Other names: B2M, Beta-2-microglobulin
Entrez ID:
2ms
High-specificity CRISPR-mediated genome engineering in anti-BCMA allogeneic CAR T cells suppresses allograft rejection in preclinical models. (PubMed, Cancer Immunol Res)
CB-011 cells were protected from natural killer (NK) cell-mediated cytotoxicity in vitro and in vivo due to endogenous promoter-driven expression of B2M-HLA-E. Potent antitumor efficacy, when combined with an immune-cloaking armoring strategy to dampen allograft rejection, offers optimized therapeutic potential in multiple myeloma.
Preclinical • Journal • CAR T-Cell Therapy • IO biomarker
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B2M (Beta-2-microglobulin) • HLA-E (Major Histocompatibility Complex, Class I, E)
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B2M elevation
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CB-011
4ms
CLL-1-Targeted Allogeneic CAR-T Cells Exhibit High on-Target Specificity and Potent Cytotoxicity in Preclinical Models of Acute Myeloid Leukemia (ASH 2023)
CB-012 demonstrated highly specific and potent CLL-1-targeted cytolytic activity in vitro and in vivo. Specificity of the anti-CLL-1 scFv was further demonstrated by screening in an unbiased protein-binding study and no adverse safety signals were observed in murine models. These data support advancing the development of CB-012 into a first-in-human clinical trial for patients with r/r AML.
Preclinical • CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • B2M (Beta-2-microglobulin) • HLA-E (Major Histocompatibility Complex, Class I, E)
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PD-L1 expression • B2M elevation • B2M-HLA-E fusion
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CB-012
12ms
Digital Spatial Profiling Links Beta-2-microglobulin Expression with Immune Checkpoint Blockade Outcomes in Head and Neck Squamous Cell Carcinoma. (PubMed, Cancer Res Commun)
Our study illustrates B2M expression is associated with improved survival for immune checkpoint inhibitor (ICI)-treated HNSCC. In the current study, DSP revealed the positive association of B2M expression in the tumor compartment with immunotherapy outcomes in R/M HNSCC.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker • Checkpoint block
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PD-L1 (Programmed death ligand 1) • LAG3 (Lymphocyte Activating 3) • B2M (Beta-2-microglobulin) • IL2RA (Interleukin 2 receptor, alpha) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C)
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PD-L1 expression • B2M elevation
1year
CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy engineered with next-generation CRISPR technology to resist both the immunosuppressive tumor microenvironment and immune cell-mediated rejection, for patients with relapsed or refractory acute myeloid leukemia (AACR 2023)
CLL-1 is a compelling therapeutic target as it is highly expressed on AML tumor cells and leukemic stem cells, but not expressed on hematopoietic stem cells. It has also been established as a target in human proof-of-concept studies. CB-012 demonstrated potent and specific CLL-1-targeted cytolytic activity, and the genome-editing strategy employed to manufacture and armor CB-012 conferred a functional advantage in the context of the potentially immunosuppressive tumor microenvironment associated with r/r AML.
Clinical • CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker • Immune cell
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PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • B2M (Beta-2-microglobulin) • HLA-E (Major Histocompatibility Complex, Class I, E)
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PD-L1 expression • B2M elevation • B2M-HLA-E fusion
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CB-012
over1year
CB-011, a BCMA-Specific Allogeneic CAR-T Cell Therapy, Engineered with Next-Generation CRISPR Technology to Express an HLA-E Fusion Transgene to Prevent Immune Cell-Mediated Rejection, for r/r Multiple Myeloma (TCT-ASTCT-CIBMTR 2023)
These studies support the safety and efficacy profiles of CB-011 for an upcoming first-in-human phase 1 clinical trial evaluating these allogeneic BCMA-specific CAR-T cells in patients with r/r MM.
CAR T-Cell Therapy • IO biomarker • Immune cell
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CD19 (CD19 Molecule) • B2M (Beta-2-microglobulin) • HLA-E (Major Histocompatibility Complex, Class I, E)
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B2M elevation
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CB-011
over1year
Pre-T cell receptor Self-MHC Sampling Restricts Thymocyte Dedifferentiation. (PubMed, Nature)
Compensatory upregulation of diverse MHC class Ib proteins in B2m/H2-Ab1 MHC knockout mice partially safeguards in vivo thymocyte progression although, with ageing, disseminated DP thymic tumours may develop. Thus, beyond fostering β chain repertoire broadening for subsequent αβ TCR utilization, preTCR-pMHC interaction limits cellular plasticity to facilitate normal thymocyte differentiation and proliferation that, if absent, introduces developmental vulnerabilities.
Journal
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B2M (Beta-2-microglobulin)
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B2M elevation
almost2years
ACCURACY AND PROGNOSTIC IMPACT OF FDG PET/CT AND BIOPSY IN BONE MARROW ASSESSMENT OF FOLLICULAR LYMPHOMA AT DIAGNOSIS: A NATION-WIDE STUDY. (EHA 2022)
Conclusion In our FL series, the combined “PET/CT or BMB positive” was the only BMI variable that showed an independent prognostic value in FL. Therefore, our data support that both procedures should be carried out in the upfront work of all suitable FL patients.
FDG PET
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B2M (Beta-2-microglobulin)
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B2M elevation
almost2years
THE PRELIMINARY SAFETY AND EFFICACY STUDY OF SC-U02, A NON-VIRAL GENOME TARGETING, ANTI-CD19 UNIVERSAL CAR-T PRODUCT, IN RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS (EHA 2022)
In this study, we conducted a Non-viral Genome Targeting approach for producing the allogeneic anti-CD19 CAR-T cells (nvGT UCART19), SC-U02...Tocilizumab was administered during CRS for this patient, and the symptom was reversed afterwards...However, due to limited cases reported, SC-U02’s safety and efficacy profile still needs to be decided. The research is ongoing and 6×10 8 cell dose level will be assessed later on.
Clinical • IO biomarker
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IL6 (Interleukin 6) • B2M (Beta-2-microglobulin) • HLA-E (Major Histocompatibility Complex, Class I, E)
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B2M elevation
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Actemra IV (tocilizumab) • UCART19
over2years
Performance of Standard Prognostic Models in Older Adults Receiving Ibrutinib for Treatment-Naïve (TN) Chronic Lymphocytic Leukemia (CLL): A Post Hoc Analysis of Alliance A041202 Phase 3 Trial (ASH 2021)
Methods Pts were randomized to bendamustine plus rituximab (BR group) or ibrutinib-based therapy with or without rituximab (I/IR group). IGHV mutation status and B2M had independent prognostic value in our dataset. Support: U10CA180821, U10CA180882, U24CA196171; Pharmacyclics, An AbbVie Company Clinicaltrials.gov identifier: NCT01886872
Clinical • P3 data • Retrospective data • IO biomarker
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TP53 (Tumor protein P53) • IGH (Immunoglobulin Heavy Locus) • B2M (Beta-2-microglobulin)
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TP53 mutation • LDH elevation • IGH mutation • B2M elevation
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Imbruvica (ibrutinib) • Rituxan (rituximab) • bendamustine
almost3years
B2M gene expression shapes the immune landscape of lung adenocarcinoma and determines the response to immunotherapy. (PubMed, Immunology)
Finally, we provide insight into the roles of transcription factors and KRAS mutations in B2M expression and the anticancer immune response. In conclusion, genetic and epigenetic regulation of B2M fundamentally shapes the NSCLC immune microenvironment and may determine the response to checkpoint blockade-based immunotherapy.
Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • B2M (Beta-2-microglobulin)
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KRAS mutation • TMB-H • B2M elevation