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- [VIRTUAL] Primary Cutaneous Gamma/Delta T-cell Lymphoma with Cellular Coexpression of Alpha/Beta T-cell Receptor () - Dec 2, 2020 - Abstract #ASDP2020ASDP_217;
Median survival for this aggressive lymphoma is ~12 months. Unfortunately for the patient presented, disease progressed rapidly, and he passed away three months after diagnosis.
- [VIRTUAL] Primary Cutaneous CD4+ Small/Medium Pleomorphic T-cell Lymphoproliferative Disorder Presenting as Subcutaneous Granuloma Annulare () - Dec 2, 2020 - Abstract #ASDP2020ASDP_197;
The patient will undergo radiotherapy for local control. In conclusion, we present a rare case that demonstrates both clinical and histologic pitfalls of diagnosing PCSM-TCL.
- | Journal: Phenotypic and functional characterization of natural killer cells in rheumatoid arthritis-regulation with interleukin-15. (Pubmed Central) - Dec 2, 2020
Taken together, our study demonstrated differential expression of various NK receptors in RA patients. NKp46, CD158e, and perforin expression on NK cells may serve as markers of RA severity.
- || Clinical, Journal: Sphingosine signaling dysfunction in airway cells as a potential contributor to progression from protracted bacterial bronchitis to bronchiectasis in children. (Pubmed Central) - Dec 1, 2020
Children with PBB and BE share similar S1P-associated gene expression profiles. AM phagocytic dysfunction and inflammation in these children may occur due to dysregulated S1P signaling.
- | Journal, IO biomarker: Evaluation of serum-free media formulations in feeder cell-stimulated expansion of natural killer cells. (Pubmed Central) - Dec 1, 2020
AM phagocytic dysfunction and inflammation in these children may occur due to dysregulated S1P signaling. The AIM V + ICSR SFM system supports excellent ex vivo expansion of clinical-grade NK cells with the phenotype and function needed for adoptive immunotherapy.
- | Journal: Granzyme B Produced by Natural Killer Cells Enhances Inflammatory Response and Contributes to the Immunopathology of Cutaneous Leishmaniasis. (Pubmed Central) - Nov 27, 2020
Furthermore, an in vitro blockade of granzyme B was observed to decrease TNF production. Our data, taken together, suggest an important role by NK cells in inducing inflammation in CL, thereby contributing to disease immunopathology.
- || fluorouracil topical / Generic mfg.
Clinical, Clinical data, Journal, PD(L)-1 Biomarker, IO Biomarker: Tumor-infiltrating podoplanin cells in gastric cancer: clinical outcomes and association with immune contexture. (Pubmed Central) - Nov 27, 2020
We demonstrated that tPDPNs high subgroup experienced worse overall survival and disease-free survival, and indicated inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy (ACT) in gastric cancer...This study revealed that the abundance of tPDPNs could identify an immunoevasive contexture and might be applied as an independent predictor for poor prognosis and suboptimal ACT responsiveness. Thus, we recommended tPDPNs as a promising therapeutic target in gastric cancer.
- | Journal: Collagen XVII Processing and Blistering Skin Diseases. (Pubmed Central) - Nov 27, 2020
Interestingly, cleavage of COL17 may induce neoepitopes on the proteolysed fragments, and such induction is associated with dynamic structural changes. This review summarizes the current understanding of cleavage of COL17, and how such cleavage relates to blistering skin diseases.
- | Retrospective data, Journal, IO Biomarker: Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy. (Pubmed Central) - Nov 25, 2020
These results suggest that SIRT is a better candidate than TACE to be combined with immunotherapy for treatment of HCC. Evaluation of the optimal doses for SIRT for producing an immunogenic effect and the type of immunotherapy to be used require further evaluation in prospective studies.
- | Biomarker, Journal: Aberrantly Methylated and Expressed Genes as Prognostic Epigenetic Biomarkers for Colon Cancer. (Pubmed Central) - Nov 25, 2020
From among the 10 epigenetic biomarkers, GZMB might serve as a tumor suppressor and function in several immune-related pathways in CC. Prognostic models based on GZMB expression and/or methylation would be significant for patients with CC.
- [VIRTUAL] Clinical Implication of PD-L1 Expression in Gallbladder Cancer () - Nov 21, 2020 - Abstract #IHPBA2020IHPBA_605;
PD-L1 expression is a useful biomarker for advanced GBC. The subgroup of high PD-L1 with high CD8+ TIL at invasive front of tumor would be potential therapeutic target for PD-1/PD-L1 checkpoint inhibitors.
- ||| Clinical: Found it fascinating on the activity pre/post CAR T, any hypotheses why this is? Why a different modality but same target has efficacy (bettter) vs. a repeat with same modaltiy (CAR T reinfusion)? Do B-cells become resistant to GranzymeB killing from CAR T vs. CD19 loss? (Twitter) - Nov 19, 2020
- | Journal: Inverse relationship between CD40L expression and cytolytic molecule expression by CD8CXCR5 T follicular cytotoxic cells in colorectal cancer. (Pubmed Central) - Nov 19, 2020
Interestingly, the levels of perforin and granzyme B expression by tumor-infiltrating Tfc cells were inversely correlated with the level of CD40L expression by tumor-infiltrating Tfc cells. Overall, we demonstrated that an inverse association existed between CD40L and cytotoxic molecule expression in Tfc cells from CRC patients.
- | Journal: Immune Cell Infiltrate in Chronic-Active Antibody-Mediated Rejection. (Pubmed Central) - Nov 19, 2020
Remarkably, increased numbers of CD3FoxP3 cells in the TI compartment were associated with decreased graft survival (p = 0.004). Renal allograft biopsies showing c-aABMR show a predominance of infiltrating CD8 T cells, and increased numbers of interstitial FoxP3 T cells are associated with inferior allograft survival.
- | Journal: Synaptic secretion from human natural killer cells is diverse and includes supramolecular attack particles. (Pubmed Central) - Nov 18, 2020
A similar number of SMAPs were secreted per cell for both NK cells and CTLs, but NK cell SMAPs were larger. These data establish an unexpected diversity in NK cell synaptic secretions.
- | Journal, IO Biomarker: Characterization of immunoreactivity with whole-slide imaging and digital analysis in high-grade serous ovarian cancer. (Pubmed Central) - Nov 18, 2020
The combined positivity of CD8 and granzyme B warrants further investigation with respect to predicting response to immune therapy. Neoadjuvant chemotherapy may have an effect on the tumor microenvironment and therefore on the response to immuno-oncologic or chemotherapy treatments.
- | Preclinical, Journal: Local mucosal immunization of self-assembled nanofibers elicits robust antitumor effects in an orthotopic model of mouse genital tumors. (Pubmed Central) - Nov 14, 2020
The levels of IFN-γ, the chemokines CXCL9 and CXCL10, and CXCR3+CD8+ T cells were significantly increased in tumor tissues, which may account for the improved recruitment of effector T cells into the tumor. Local mucosal immunization of nanofibers via the intravaginal route represents a new and promising vaccination strategy for the treatment of genital tumor lesions such as cervical cancer.
- ||||| PD(L)-1 Biomarker, IO Biomarker: Working w @colin_thalhofer @AndrewWeinber14 @BernardAFox et al @ChilesResearch @agon_ox on strategy to silence PD-1 expression in an expanded CD39/CD103+ TIL product enriched for Tu reactivity by using RNAi INTASYL™ compounds that increased IFN-g TNF-α and Granzyme-b #SITC2020 (Twitter) - Nov 13, 2020
- | Journal: Respiratory syncytial virus reduces STAT3 phosphorylation in human memory CD8 T cells stimulated with IL-21. (Pubmed Central) - Nov 12, 2020
In addition, RSV decreases granzyme B production by memory CD8 T cells, reducing its cytotoxic activity against RSV-infected epithelial pulmonary cell lines. Together, these data indicate that RSV modulates the IL-21/STAT3 pathway in human memory CD8 T cells, and this could be a mechanism to be further explored to improve the memory response against the infection.
- | Journal: Distinct Features of Canine Non-conventional CD4CD8α Double-Negative TCRαβ vs. TCRγδ T Cells. (Pubmed Central) - Nov 12, 2020
In conclusion, this study identifies two dn T cell subsets in the dog: (i) a large (~7.5% in Peyer's patches, ~15% in lung) population of TCRαβCD4CD8α dn T cells with subpopulations thereof showing an activated phenotype, high expression of FoxP3 or GATA-3 as well as production of IFN-γ or IL-17A and (ii) a small TCRγδCD4CD8α dn T cell subset also expressing GATA-3 without production of IFN-γ or IL-17A. It will be exciting to unravel the function of each subset during immune homeostasis and diseases of dogs.
- | Preclinical, Journal: The TreaT-Assay: A Novel Urine-Derived Donor Kidney Cell-Based Assay for Prediction of Kidney Transplantation Outcome. (Pubmed Central) - Nov 12, 2020
Frequencies of pre-transplant CD161 alloreactive CD4 T-cells and granzyme B producing alloreactive CD8 T-cells were substantially higher in patients with early acute rejection compared to patients without complications. In conclusion, we established a novel assay for the assessment of donor-reactive memory T-cells based on kidney cells with the potential to predict early acute rejection and post-transplant eGFR.
- | Journal: Functional characterization of grass carp (Ctenopharyngodon idella) interleukin-2 in head kidney leukocytes. (Pubmed Central) - Nov 12, 2020
Results showed that rgcIL2 treatment increased the mRNA expression of foxp3, cd25l, ifng2, il12p35, tbet, tnfa, il2, il4/13a, il4/13b and gata3l in HKLs, implying the regulatory roles of Il-2 in the expression of these immune genes and its possible involvement in differentiation of Treg and Th1/2 cells. These observations together with the related studies in other fishes suggest the existence of cytotoxic cells, Treg and Th1/2 subpopulations in fish species and the functional roles of Il-2 in these cells.
- || Opdivo (nivolumab) / Ono Pharma, BMS
Clinical, Journal, PD(L)-1 Biomarker, IO Biomarker: Immunological effects of nivolumab immunotherapy in patients with oral cavity squamous cell carcinoma. (Pubmed Central) - Nov 12, 2020
These observations together with the related studies in other fishes suggest the existence of cytotoxic cells, Treg and Th1/2 subpopulations in fish species and the functional roles of Il-2 in these cells. These results show nivolumab causes opposing effects on CD4 and CD8 cell populations, with CD4 cell levels declining but increasing the proportion of Treg cells, and unconventional CD8 T-cell levels increasing with increased expression of immune mediators by CD8 T-cell subpopulations.
- [VIRTUAL] Indolent cutaneous T-cell lymphoid proliferations of the nose region - a novel diagnostic algorithm and molecular description () - Nov 9, 2020 - Abstract #ECP2020ECP_3432;
Study presents the first molecular description of pc-CD4+TCLPD and pc-acral-CD8+TCL. We report a novel FOXP1 fusion, which requires confirmation in a larger study.
- [VIRTUAL] Multiplexed immunohistochemistry for immune cell phaenotyping, quantification and spatial localisation in a rare tumour, clear cell ovarian cancer () - Nov 9, 2020 - Abstract #ECP2020ECP_3393;
Conclusion One third of CCOC are “immune excluded”. However when present, the effector to suppressor balance of both T cells (GrzB+/FoxP3+) and macrophages (CD68+/CD163+) is in favor of anti-tumor immune response.
- [VIRTUAL] Indolent cutaneous T-cell lymphoid proliferations of the nose region - a novel diagnostic algorithm and molecular description () - Nov 9, 2020 - Abstract #ECP2020ECP_1867;
Study presents the first molecular description of pc-CD4+TCLPD and pc-acral-CD8+TCL. We report a novel FOXP1 fusion, which requires confirmation in a larger study.
- [VIRTUAL] Multiplexed immunohistochemistry for immune cell phaenotyping, quantification and spatial localisation in a rare tumour, clear cell ovarian cancer () - Nov 9, 2020 - Abstract #ECP2020ECP_1828;
Conclusion One third of CCOC are “immune excluded”. However when present, the effector to suppressor balance of both T cells (GrzB+/FoxP3+) and macrophages (CD68+/CD163+) is in favor of anti-tumor immune response.
- [VIRTUAL] Indolent cutaneous T-cell lymphoid proliferations of the nose region - a novel diagnostic algorithm and molecular description () - Nov 9, 2020 - Abstract #ECP2020ECP_192;
Study presents the first molecular description of pc-CD4+TCLPD and pc-acral-CD8+TCL. We report a novel FOXP1 fusion, which requires confirmation in a larger study.
- [VIRTUAL] Multiplexed immunohistochemistry for immune cell phaenotyping, quantification and spatial localisation in a rare tumour, clear cell ovarian cancer () - Nov 9, 2020 - Abstract #ECP2020ECP_153;
Conclusion One third of CCOC are “immune excluded”. However when present, the effector to suppressor balance of both T cells (GrzB+/FoxP3+) and macrophages (CD68+/CD163+) is in favor of anti-tumor immune response.
- | Hiltonol (poly-ICLC) / Oncovir
Journal, IO Biomarker: Dendritic Cells Generated in the Presence of Platelet Lysate Have a Reduced Type 1 Polarization Capacity. (Pubmed Central) - Nov 7, 2020
Based on these findings, the use of PL as an alternative serum supplement for generation of monocyte-derived DC anti-tumor vaccines is questionable. Abbreviations: Ag: antigen; CCL: chemokine ligand; CCR: chemokine receptor; DC: dendritic cells; DC-SIGN: dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin; FBS: fetal bovine serum; GMP: good manufacturing practice; IFN: interferon; IL: interleukin; MPLA: monophosphoryl lipid A; PGE: prostaglandin E; pI:C: polyinosinic:polycytidylic acid; pl: platelet lysate; sf: serum free; TLR: toll-like receptor; TNF: tumor necrosis factor.
- | Journal: IL-21 regulates SOCS1 expression in autoreactive CD8 T cells but is not required for acquisition of CTL activity in the islets of non-obese diabetic mice. (Pubmed Central) - Nov 7, 2020
However IL-21R deficiency did not affect islet CD8 T cell proliferation or expression of granzyme B or IFNγ. Together these data indicate that autoreactive CD8 T cells respond to IL-21 and not type I IFNs in the islets of NOD mice, but neither IFNAR1 nor IL-21R are required for islet intrinsic CTL maturation.
- | Journal, PD(L)-1 Biomarker, IO Biomarker: Synergistic Effects of Interferon-γ and Vitamin D Signaling in Induction of ILT-3PDL-1 Tolerogenic Dendritic Cells. (Pubmed Central) - Nov 7, 2020
Inhibition of MEK/ERK and PI3K/mTOR pathways significantly reduced the expression of ILT-3 and PDL-1 on γ/DDCs. In summary, we present the first evidence for existing synergy between IFN-γ and vit D in shaping a unique tolerogenic DC activation state.
- | Journal: Vaccine-Induced Antibodies Mediate Higher Antibody-Dependent Cellular Cytotoxicity After Interleukin-15 Pretreatment of Natural Killer Effector Cells. (Pubmed Central) - Nov 7, 2020
We also found that using a 4-fold dilution series of plasma and subtraction of pre-vaccination responses resulted in lowest response rates among placebo recipients and significant separation between treatment groups. This represents the first attempt to utilize IL-15-treated effector cells and optimized analytical approaches to improve the detection of HIV-1 vaccine-induced ADCC responses and will inform analyses of future HIV vaccine clinical trials.
- | Journal: Apoptosis in idiopathic inflammatory myopathies with partial invasion; a role for CD8+ cytotoxic T cells? (Pubmed Central) - Nov 6, 2020
In contrast, apoptotic myonuclei were rare in dermatomyositis and absent in controls. The findings confirm that apoptosis occurs in idiopathic inflammatory myopathies and support that it is mediated by CD8+ cytotoxic T- cells, acting in parallel to the process of partial invasion.
- Observational data, Journal, IO Biomarker: CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS. (Pubmed Central) - Nov 6, 2020
P=N/A
Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach. ClinicalTrials.gov, NCT03955887.
- [VIRTUAL] Using Allogeneic, Off-the-Shelf, Sars-Cov-2-Specific T Cells to Treat High Risk Patients with COVID-19 () - Nov 5, 2020 - Abstract #ASH2020ASH_5641;
SARS-CoV-2 VSTs generated from convalescent individuals are Th1-polarized, polyfunctional and selectively able to kill viral antigen-expressing targets with no auto- or alloreactivity, indicative of both their selectivity and safety for clinical use. We are rapidly advancing this product to the clinic for administration in a randomized clinical trial (VSTs+SOC vs SOC) to prevent the development of severe disease in high risk hospitalized patients such as those post-transplant or therapy for hematologic malignancy Figure 1: SARS-CoV-2 Specific T cells Demonstrate Selective Cytolytic Activity against viral antigen-expressing targets.
- Darzalex IV (daratumumab) / J&J, talquetamab (JNJ-64407564) / J&J
[VIRTUAL] Mechanisms of Resistance and Determinants of Response of the GPRC5D-Targeting T-Cell Redirecting Bispecific Antibody JNJ-7564 in Multiple Myeloma (Channel 11 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_4456;
We show that tumor-related factors, such as GPRC5D expression, as well as differences in the composition of the BM microenvironment, including E:T ratio, frequency of PD-1+ or HLA-DR+ T-cells or immune-suppressing Tregs or BMSCs, contribute to the variability in response to JNJ-7564. Our data indicate that strategies aiming at optimizing E:T ratio (e.g. induction therapy) or Treg depletion, may improve response to T-cell redirecting antibodies in MM.
- [VIRTUAL] Using Allogeneic, Off-the-Shelf, Sars-Cov-2-Specific T Cells to Treat High Risk Patients with COVID-19 (Channel 21 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_4402;
SARS-CoV-2 VSTs generated from convalescent individuals are Th1-polarized, polyfunctional and selectively able to kill viral antigen-expressing targets with no auto- or alloreactivity, indicative of both their selectivity and safety for clinical use. We are rapidly advancing this product to the clinic for administration in a randomized clinical trial (VSTs+SOC vs SOC) to prevent the development of severe disease in high risk hospitalized patients such as those post-transplant or therapy for hematologic malignancy Figure 1: SARS-CoV-2 Specific T cells Demonstrate Selective Cytolytic Activity against viral antigen-expressing targets.
- Kymriah (tisagenlecleucel-T) / Novartis
[VIRTUAL] The Enhanced Functionality of Low-Affinity CD19 CAR T Cells Is Associated with Activation Priming and Polyfunctional Cytokine Phenotype (Channel 21 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_4345;
We have recently described a low-affinity second-generation anti-CD19 Chimeric Antigen Receptor (CAR) (CAT), characterized by faster antigen dissociation rate which showed enhanced expansion, cytotoxicity and anti-tumour efficacy compared with the high affinity (FMC63 based) CAR used in Tisagenlecleucel in pre-clinical models...Our results show that the potent and long-term anti-tumour responses observed with CAT may be sustained by the establishment of CAR T cells self-reinforcing circuits activated through polyfunctional cytokine crosstalk. This work may inform the future design of versatile CAR T cells, capable of balancing safety, efficacy and long-term persistence.
- tebotelimab (MGD013) / MacroGenics, Opdivo (nivolumab) / Ono Pharma, BMS
[VIRTUAL] A Phase 1, Open-Label Study of MGD013, a Bispecific DART® Molecule Binding PD‑1 and LAG‑3 in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_3820;
PD-1 targeted therapy with nivolumab in patients (pts) with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) has yielded modest efficacy (2). MGD013, a novel molecule designed to coordinately block PD-1 and LAG-3, has preliminarily demonstrated an acceptable safety profile and encouraging early evidence of anti-tumor activity in R/R DLBCL pts with and without prior treatment with CAR T. Biomarker analyses confirmed expression of both PD-1 and LAG-3 axes in responding pts with evidence of pharmacodynamic responses consistent with the ability of MGD013 to enhance T-cell function.
- AFM13 / Affimed
[VIRTUAL] Title: Clinical and Biological Evaluation of the Novel CD30/CD16A Tetravalent Bispecific Antibody (AFM13) in Relapsed or Refractory CD30-Positive Lymphoma with Cutaneous Presentation: A Biomarker Phase Ib/IIa Study (NCT03192202) (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_3769;
P1/2
In addition, biological changes in NK infiltration and activation in the PB and tissue biopsy correlated with response. These data are the first to demonstrate that innate cell engagers modulate NK and T cell populations in the peripheral blood and tumor from patients and to determine that such changes are associated with patient benefit.
- [VIRTUAL] Cytomegalovirus Promotes Aberrant Memory CD4 T Cell Differentiation and Immune Function after Allogeneic Stem Cell Transplantation (Channel 23 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_3150;
This cell population is expanded even in the absence of detectable CMV reactivation post SCT and can be observed for several years following transplant. We thus provide a potential mechanism for the immunodeficiency and broad increase in infection mortality invoked by CMV exposure.
- mezagitamab (TAK-079) / Takeda
[VIRTUAL] Mezagitamab Induces Immunomodulatory Effect in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) (Channel 3 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_3042;
P1/2
Conclusions Chronic treatment with mezagitamab is immunomodulatory in patients with RRMM, which is associated with reductions in tumor burden, subpopulations of B and T regulatory cells, and characterized by conventional NK and T cells exhibiting an activated, proliferative and effector phenotype. The immune landscape changes observed is consistent with the immunologic concept of converting the tumor microenvironment from cold-to-hot and highlights a key mechanistic effect of mezagitamab.
- orvacabtagene autoleucel (JCARH125) / BMS
[VIRTUAL] Orvacabtagene Autoleucel (orva-cel; JCARH125): A Fully Human BCMA-Targeted Second-Generation CAR T Cell Product Characterized By a Predominant Central Memory Phenotype with High in Vitro and In Vivo Proliferative Potential and Sustained In Vivo Persistence (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2822;
P1/2
Conclusions : The orva-cel manufacturing process results in drug products characterized by highly pure T cells, with high frequencies of early memory and polyfunctional CAR+ T cells. Orva-cel drug products showed robust antigen-specific degranulation, production of multiple cytokines, sustained in vitro and in vivo proliferation, and in vivo persistence.
- [VIRTUAL] A Fully-Human Armored BCMA CAR Boosts Function of CD4+ CAR-T Cells and Resists TGF-β Suppression in Pre-Clinical Models of Multiple Myeloma (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2801;
In conclusion, we have designed and characterized a new fully-human BCMA2-TbnegCAR, with a novel scFv that exhibits robust proliferative capacity and persistent cytotoxicity, and remains functionally resistant to the immunosuppressive effects of TGF-β. This novel BCMA CAR can potentially improve the effectiveness and durability of the current BCMA CAR-T cell therapy.
- Revlimid (lenalidomide) / BMS
[VIRTUAL] Immune Cell Profiles in Patients Treated with Lenalidomide and Alternate Day Prednisolone Maintenance Post Upfront ASCT for Multiple Myeloma (LEOPARD Trial) (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2748;
Subsequently, durable responses to post-ASCT lenalidomide maintenance were associated with a cytotoxic, controlled immune response whereas early relapse was characterised by a more uncontrolled inflammatory response and the emergence of B-reg-like cells prior to relapse. We conclude that immune profiling at baseline and after initiation of therapy may help to predict a more sustained response to lenalidomide maintenance enabling pre-emptive tailored treatment decisions.
- K-NK003 / Kiadis
[VIRTUAL] A Phase I Trial of Incorporating Natural Killer (K-NK) Cells for Patients with Chronic Myeloid Leukemia (CML) and Molecular Residual Disease after Tyrosine Kinase Inhibitor (TKI) Therapy (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2615;
Kiadis K-NK003 cells are off-the-shelf NK cells from a universal donor expanded using PM21, proprietary membrane particles modified to express membrane bound IL-21 and 4-1bb ligand...Patients must have been on their most recent TKI consistently for at least 6 months prior to enrollment on study and must be expected to remain on current TKI for the duration of the study. Patients with current accelerated or blast crisis phase disease will be excluded.
- KTX-201 / Kymera Therap
[VIRTUAL] Mechanisms of the Anti-Tumor Activity of STAT3 Degraders in Lymphoma (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2554;
Collectively, our data demonstrate that significant STAT3 degradation for a limited time during dosing interval with KTX-201 in ALCL promotes early changes in key signaling nodes involved with proliferation and cytokine stimulation, followed by profound changes in apoptotic proteins. By integrating mechanistic biology with a deep understanding of PK/PD and efficacy, this study provides a foundation for the clinical development of STAT3 degraders using intermittent dosing regimen for treatment of PTCL and other STAT3-dependent heme malignancies.
- [VIRTUAL] Clinicopathology, Disease Progression/Transformation and Genomic Alterations of Indolent T-Cell Lymphoproliferative Disorder of the Gastrointestinal Tract (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2547;
ITCLD-GT is generally inert, but it may develop with an increased Ki67 proliferation index in the late stage or even turn into aggressive DLBCL. We characterized the genomic alterations in ITCLD-GT and revealed its molecular pathogenesis and progression, which might be helpful for diagnosis, prognosis and treatment of this rare lymphoid neoplasm.
- Blincyto (blinatumomab) / Astellas, Amgen, AMG 562 / Amgen
[VIRTUAL] Treatment-Free Intervals Mitigate T-Cell Exhaustion Induced By Continuous CD19xCD3-BiTE® Construct Stimulation in Vitro (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2401;
Currently, T cells from patients receiving blinatumomab are being analyzed to confirm the clinical relevance of our findings. Furthermore, RNA-Seq of continuously vs. intermittently AMG 562-exposed T cells will help us to understand underlying transcriptional mechanisms of BiTE® construct induced T-cell exhaustion.