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    BIOMARKER:

    LAMP1 expression

    i
    Other names: Lysosomal Associated Membrane Protein 1, Lysosome-Associated Membrane Glycoprotein 1, Lysosome-Associated Membrane Protein 1, CD107 Antigen-Like Family Member A, CD107a, LAMP-1, Lysosomal-Associated Membrane Protein 1, CD107a Antigen, LGP120, LAMPA, LAMP1
    Entrez ID:
    3916
    5d
    Dendrobium nobile Lindl. alkaloids protect CCl4-induced acute liver injury via upregulating LAMP1 expression and activating autophagy flux. (PubMed, J Nat Med)
    While pretreatment of cells with lysosomal inhibitor chloroquine weakened mitochondrial protection elicited by DNLA, overexpression of mitochondrial-targeted SOD2 in AML-12 cells significantly blocked CCl4 induced downregulation of LAMP1, thereby improving lysosome integrity and promoting lysosome dependent autophagy, suggesting that there may exist a bidirectional regulation between mitochondrial ROS and lysosome-autophagy activation. Collectively, these results demonstrated that DNLA can protect the liver injury mediated by dysregulation of lysosome-autophagy process through promoting ROS-lysosome-autophagy axis and improving mitochondrial damage.
    Journal
    |
    LAMP1 (Lysosomal Associated Membrane Protein 1) • SOD2 (Superoxide Dismutase 2)
    |
    LAMP1 expression
    |
    chloroquine phosphate
    5d
    Biomarker Analysis of phase II CAVE2 GOIM study of the combination of avelumab plus cetuximab as rechallenge strategy in pre-treated RAS/BRAF wild type metastatic colorectal cancer patients (AIOM 2024)
    These preliminary findings suggest that evaluation of in vitro cytotoxicity together with CD107a expression in mCRC patients derived PBMC could be a useful tool to identify early responders after only 8 weeks of treatment with cetuximab plus avelumab. In addition, we aim to further investigate the potential role of CCL5 secreted by peripheral immune cells and its cut-off as a predictive biomarker of mCRC progression in a larger cohort of patients.
    Clinical • P2 data • PD(L)-1 Biomarker • Metastases
    |
    BRAF (B-raf proto-oncogene) • RAS (Rat Sarcoma Virus) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    BRAF wild-type • LAMP1 expression
    |
    FoundationOne® Liquid CDx
    |
    Erbitux (cetuximab) • Bavencio (avelumab)
    29d
    A study on the effects of Anti-GM1 on the differentiation and cytotoxic activity of NK cells in nude mice (PubMed, Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi)
    Conclusion NK cells can infiltrate into human renal cancer tissue and can secrete GzmB, exerting natural killing effects. Anti-GM1 can promote the maturation of NK cells but inhibit the killing activity of NK cells, which is related to its inhibition of NK cell CD107a expression and suppression of NK cell IFN-γ and GzmB secretion.
    Preclinical • Journal • IO biomarker
    |
    IFNG (Interferon, gamma) • CD27 (CD27 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1) • GZMB (Granzyme B) • ITGAM (Integrin, alpha M)
    |
    LAMP1 expression • CD27 expression
    1m
    Evaluation of Fluoxetine and Cytotoxic Lysosomal Stress in Glioma (FLIRT) (clinicaltrials.gov)
    P1, N=30, Recruiting, Duke University | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    LAMP1 expression • IDH wild-type
    |
    temozolomide • fluoxetine
    3ms
    Oncolytic virotherapy augments self-maintaining natural killer cell line cytotoxicity against neuroblastoma. (PubMed, Cancer Immunol Immunother)
    To the best of our knowledge, these investigations are the first to demonstrate the effects of an oncolytic virus combined with self-maintaining NK cells in neuroblastoma and the priming effect of neuroblastoma on NK cells. The current studies provide a deeper understanding of the relation between NK cells and neuroblastoma and these data suggest that oHSV increases NK cell cytotoxicity towards neuroblastoma.
    Preclinical • Journal • Oncolytic virus • IO biomarker
    |
    MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    MYCN amplification • LAMP1 expression
    7ms
    Preparation of a dual-specific antibody targeting human CD123 and exploration of its anti-acute myeloid leukemia effects (PubMed, Zhonghua Xue Ye Xue Za Zhi)
    In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123(+) tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • TNFA (Tumor Necrosis Factor-Alpha) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL2RA (Interleukin 2 receptor, alpha) • CD69 (CD69 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    LAMP1 expression • CD123 expression • IL3RA expression
    7ms
    T-Cell-Based Platform for Functional Screening of T-Cell Receptors Identified in Single-Cell RNA Sequencing Data Sets of Tumor-Infiltrating T-Cells. (PubMed, Bio Protoc)
    • Applicable to TCRs from CD8+ and CD4+ tumor-infiltrating T-cells originating from patient-derived tumor samples and syngeneic mouse tumor models. • Rapid flow cytometric detection of T-cell activation by means of TNFα and CD107a expression after a 5 h T-cell/tumor cell co-cultivation.
    Journal • IO biomarker
    |
    CD8 (cluster of differentiation 8) • TNFA (Tumor Necrosis Factor-Alpha) • CD4 (CD4 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    LAMP1 expression
    8ms
    Abemaciclib and Vacuolin-1 decrease aggregate-prone TDP-43 accumulation by accelerating autophagic flux. (PubMed, Biochem Biophys Rep)
    A treatment with the VPS34 inhibitor wortmannin (WM) suppressed Abe-/Vac-facilitated autophagic flux and the degradation of GFP-tagged aggregate-prone TDP-43. Collectively, these results suggest that Abe and Vac degrade aggregate-prone TDP-43 by accelerating autophagosome formation and autophagosome-lysosome fusion through the formation of PI(3)P.
    Journal
    |
    LAMP1 (Lysosomal Associated Membrane Protein 1) • TARDBP (TAR DNA Binding Protein) • TSG101 (Tumor Susceptibility 101)
    |
    LAMP1 expression
    |
    Verzenio (abemaciclib)
    8ms
    Blueberry: Effect of Blueberries on Immunity and Response to Flu Vaccination (clinicaltrials.gov)
    P=N/A, N=52, Active, not recruiting, Loma Linda University | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial completion date • Trial primary completion date
    |
    LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    LAMP1 expression
    8ms
    The ω-3 polyunsaturated fatty acid docosahexaenoic acid enhances NK-cell antitumor effector functions. (PubMed, Cancer Immunol Res)
    The PGC-1α inhibitor SR-18292 in vitro and NK cell-specific knockout of PGC-1α in mice reversed the antitumour effects of DHA. In summary, our findings broaden the current knowledge on how DHA supplementation protects against cancer growth from the perspective of immunomodulation by upregulating PGC-1α signalling-mediated mitochondrial OXPHOS activity in NK cells.
    Journal
    |
    IFNG (Interferon, gamma) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    IFNG expression • LAMP1 expression
    8ms
    Extended characterization of anti-CD19 CAR T cell products manufactured at the point of care using the CliniMACS Prodigy system: comparison of donor sources and process duration. (PubMed, Cytotherapy)
    This study demonstrates the possibility of using the CliniMACS Prodigy system with a shortened 7-day production cycle to produce sufficient amount of functional CAR-T cells. CAR transduction efficiency can be measured indirectly via functional assays.
    Journal • CAR T-Cell Therapy • IO biomarker
    |
    LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    LAMP1 expression
    9ms
    Artificial Targets: a versatile cell-free platform to characterize CAR T cell function in vitro. (PubMed, Front Immunol)
    Finally, Artificial Targets demonstrated flexibility to engage multiple costimulatory molecules that can synergistically enhance the CAR T cell function and represented a powerful tool for modulating CAR T cell responses. Collectively, our results show that Artificial Targets can specifically activate CAR T cells for essential effector functions that could significantly advance standardization of functional assessment of CAR T cells, from early development to clinical applications.
    Preclinical • Journal • CAR T-Cell Therapy • IO biomarker
    |
    CD69 (CD69 Molecule) • TNFRSF9 (TNF Receptor Superfamily Member 9) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    LAMP1 expression
    9ms
    Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate and High-Risk Prostate Cancer (clinicaltrials.gov)
    P2, N=33, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2023 --> Jun 2024
    Trial completion date • IO biomarker
    |
    AR (Androgen receptor) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • CD276 (CD276 Molecule) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TNFRSF9 (TNF Receptor Superfamily Member 9) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    CD276 expression • LAG3 expression • HAVCR2 expression • LAMP1 expression
    |
    enoblituzumab (MGA271)
    9ms
    HEAT: Trial of Neoadjuvant Enoblituzumab vs SOC in Men With High-Risk Localized Prostate Cancer (clinicaltrials.gov)
    P2, N=219, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting
    Enrollment open
    |
    PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • CD276 (CD276 Molecule) • TNFRSF9 (TNF Receptor Superfamily Member 9) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    PD-L1 expression • LAMP1 expression
    |
    enoblituzumab (MGA271)
    9ms
    Evaluation of Fluoxetine and Cytotoxic Lysosomal Stress in Glioma (FLIRT) (clinicaltrials.gov)
    P1, N=30, Recruiting, Duke University | Trial completion date: Jun 2024 --> Jun 2026 | Trial primary completion date: Dec 2023 --> Dec 2025
    Trial completion date • Trial primary completion date
    |
    LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    LAMP1 expression • IDH wild-type
    |
    temozolomide • fluoxetine
    9ms
    Stimulating T cell responses against patient-derived breast cancer cells with neoantigen peptide-loaded peripheral blood mononuclear cells. (PubMed, Cancer Immunol Immunother)
    Moreover, ALKBH6V83M and GAAI823T peptides from PC-B-148CA remarkably stimulated IFN-γ- and CD107a-positive T cells, displaying high cell-killing activity against target cancer cells. In summary, our findings underscore the successful identification of neoantigens with anti-tumor T cell functions and highlight the potential of personalized neoantigens as a promising avenue for breast cancer treatment.
    Journal • PARP Biomarker
    |
    IFNG (Interferon, gamma) • LAMP1 (Lysosomal Associated Membrane Protein 1) • SEC14L2 (SEC14 Like Lipid Binding 2)
    |
    LAMP1 expression
    10ms
    Enhancing cancer immunotherapy with Anti-NKG2D/IL-15(N72D)/Sushi fusion protein: Targeting cytotoxic immune cells and boosting IL-15 efficacy. (PubMed, Cytokine)
    The fusokine possesses the capability to stimulate the survival and multiplication of lymphocytes, as well as their ability to eliminate tumors. These characteristics have led to its consideration as a potential treatment for immunotherapy.
    Journal • IO biomarker • Immune cell
    |
    LAMP1 (Lysosomal Associated Membrane Protein 1) • GZMB (Granzyme B) • IL15 (Interleukin 15) • NKG2D (killer cell lectin like receptor K1)
    |
    LAMP1 expression
    10ms
    NUPR1 contributes to activate TFE3-dependent autophagy leading to cervical cancer proliferation. (PubMed, Heliyon)
    Overall, silencing NUPR1 reduced autophagy by inhibiting TFE3 in cervical cancer. Our results supply new evidence for the use of NUPR1 as a therapeutic target in cervical cancer.
    Journal
    |
    TFE3 (Transcription Factor Binding To IGHM Enhancer 3) • LAMP1 (Lysosomal Associated Membrane Protein 1) • LAMP2 (Lysosomal Associated Membrane Protein 2) • NUPR1 (Nuclear Protein 1 Transcriptional Regulator, Candidate Of Metastasis 1) • PI3K (Phosphoinositide 3-kinases)
    |
    LAMP1 expression • NUPR1 expression
    10ms
    Dehydrocostus lactone suppresses gastric cancer progression by targeting ACLY to inhibit fatty acid synthesis and autophagic flux. (PubMed, J Adv Res)
    Our work identified Dehy as a desirable agent for blunting abnormal lipid metabolism and highlighted its inhibitory effect on protective autophagy, suggesting the future development of Dehy as a novel therapeutic drug for GC.
    Journal
    |
    LAMP1 (Lysosomal Associated Membrane Protein 1) • ANXA5 (Annexin A5) • LAMP2 (Lysosomal Associated Membrane Protein 2)
    |
    LAMP1 expression
    |
    5-fluorouracil
    10ms
    High and selective cytotoxicity of ex vivo expanded allogeneic human natural killer cells from peripheral blood against bladder cancer: implications for natural killer cell instillation after transurethral resection of bladder tumor. (PubMed, J Exp Clin Cancer Res)
    The expanded NK cells exhibit potent cytotoxicity against BCa cells, with few toxic side effects on normal urothelial cells. In addition, NK cells recruit T cells by secreting a panel of chemokines, which supports the translational application of NK cell intravesical instillation after TURBT from bench to bedside for NMIBC treatment.
    Preclinical • Journal
    |
    IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2RA (Interleukin 2 receptor, alpha) • CD69 (CD69 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • CCL20 (C-C Motif Chemokine Ligand 20) • LAMP1 (Lysosomal Associated Membrane Protein 1) • CCL2 (Chemokine (C-C motif) ligand 2) • GZMB (Granzyme B) • NCR3LG1 (Natural Killer Cell Cytotoxicity Receptor 3 Ligand 1) • CXCL16 (C-X-C Motif Chemokine Ligand 16) • CXCL3 (C-X-C Motif Chemokine Ligand 3) • ISG20 (Interferon Stimulated Exonuclease Gene 20) • NKG2D (killer cell lectin like receptor K1) • ULBP2 (UL16 Binding Protein 2) • IL2RG (Interleukin 2 Receptor Subunit Gamma)
    |
    LAMP1 expression
    10ms
    Loss of RND3/RHOE controls entosis through LAMP1 expression in hepatocellular carcinoma. (PubMed, Cell Death Dis)
    Moreover, we found a positive correlation between the presence of entotic cells and the metastatic potential of tumors in human patient samples. Altogether, these data suggest the involvement of entosis in liver tumor progression and highlight a new perspective for entosis analysis in medicine research as a novel therapeutic target.
    Journal
    |
    CDH1 (Cadherin 1) • RHOA (Ras homolog family member A) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    LAMP1 expression
    11ms
    Sex-dependent differences in type I IFN-induced natural killer cell activation. (PubMed, Front Immunol)
    Interestingly, in addition to the extrinsic effect, we also observed NK cell-intrinsic sex differences, as female NK cells displayed higher activation levels after IFNα-stimulation and after co-culture with CL097-stimulated pDCs, suggesting higher activation of IFNα-signaling transduction in female NK cells. Taken together, the results from these studies identify both extrinsic and intrinsic sex-specific differences in Type I IFN-dependent NK cell functions, contributing to a better understanding of sex-specific differences in innate immunity.
    Journal
    |
    CD69 (CD69 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1) • IFNA1 (Interferon Alpha 1) • IFNAR1 (Interferon (alpha, beta and omega) receptor 1)
    |
    LAMP1 expression
    12ms
    Genetic Engineering of Gamma Delta (γδ) T Cells with the IL-2 Cytokine Receptor Orthogonal Pair (OIL-2R/OIL-2) As Immunotherapy for Pediatric Acute Myeloid Leukemia (TCT-ASTCT-CIBMTR 2024)
    We successfully engineered γδT cells to express an OIL-2 receptor and demonstrated their proliferation, persistence, and enhanced cytotoxicity against AML in vitro. We are in the process of evaluating safety and efficacy in a PDX model. OIL-2R γδT represents a significant step forward in the development of effective immunotherapeutic strategies for pediatric AML.
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • TNFA (Tumor Necrosis Factor-Alpha) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IL2RA (Interleukin 2 receptor, alpha) • CD69 (CD69 Molecule) • IL2 (Interleukin 2) • LAMP1 (Lysosomal Associated Membrane Protein 1) • BTLA (B And T Lymphocyte Associated) • CD40LG (CD40 ligand) • STAT5A (Signal Transducer And Activator Of Transcription 5A) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule) • ISG20 (Interferon Stimulated Exonuclease Gene 20) • KLRC1 (Killer Cell Lectin Like Receptor C1)
    |
    PD-1 expression • LAG3 expression • HAVCR2 expression • LAMP1 expression
    12ms
    Selinexor Enhances Natural Killer Cell Function Against Multiple Myeloma Cells (ASH 2023)
    This study aimed to determine whether selinexor augments NK cell activation against MM cells both alone, and in combination with the anti-CD38 antibody daratumumab. These data suggest that selinexor may promote the efficacy of NK targeted therapeutics in multiple myeloma.
    IO biomarker
    |
    XPO1 (Exportin 1) • LAMP1 (Lysosomal Associated Membrane Protein 1) • HLA-E (Major Histocompatibility Complex, Class I, E) • KLRC1 (Killer Cell Lectin Like Receptor C1) • NKG2D (killer cell lectin like receptor K1) • ULBP1 (UL16 Binding Protein 1)
    |
    CD38 expression • LAMP1 expression
    |
    Xpovio (selinexor) • Darzalex (daratumumab)
    12ms
    Ex-vivo CS1-OKT3 dual specific bivalent antibody-armed effector T cells mediate cellular immunity against multiple myeloma. (PubMed, Sci Rep)
    Here, we developed a CS1 bsAb (CS1-dbBiTE) using Click chemistry to conjugate intact anti-CS1 antibody (Elotuzumab) and anti-huOKT3 antibody at their respective hinge regions...Similarly, in MM mouse xenograft studies, armed T cells exhibited effective anti-tumor efficacy highlighted by reduced tumor burden in MM.1S tumor-bearing mice compared to controls. On the basis of these findings, the rationale for CS1 targeting by human T cells armed with CS1-dbBiTE presents a potentially effective therapeutic approach for targeting MM.
    Preclinical • Journal
    |
    LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    LAMP1 expression
    |
    Empliciti (elotuzumab)
    1year
    A randomized window of opportunity trial with dose escalation to evaluate fluoxetine and temozolomide in glioma (SNO 2023)
    All patients (control and experimental) will be offered fluoxetine post-operatively. The primary study outcome will be quantification of tumoral lysosomal stress via Lysosomal-associated membrane protein 1 (LAMP1) expression while DNA damage will be assessed via γH2A histone family member X (γH2AX) using immunohistochemistry.
    Clinical
    |
    MGMT (6-O-methylguanine-DNA methyltransferase) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    LAMP1 expression • IDH wild-type
    |
    temozolomide • fluoxetine
    1year
    A Phase 2 Study of a Novel Immunotherapy SL-701 in Adults With Recurrent Glioblastoma: Exploring the Prognostic Value of Treatment-Induced CD8+CD57+ T-cells as a Marker for Survival. (SNO 2023)
    In this study, we present updated findings from a phase 2 clinical trial (NCT02078648) evaluating SL-701+poly-ICLC+bevacizumab, where the 12-month overall survival (OS) was 50%. These qualitative differences in the immune response, detectable as early as week 8 post treatment, may serve as biomarkers for monitoring and predicting survival. Deep sequencing of SL-701-specific T-cells is planned.
    Clinical • P2 data • IO biomarker
    |
    CD8 (cluster of differentiation 8) • BIRC5 (Baculoviral IAP repeat containing 5) • CD4 (CD4 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1) • B3GAT1 (Beta-1,3-Glucuronyltransferase 1)
    |
    LAMP1 expression
    |
    Avastin (bevacizumab) • Hiltonol (poly-ICLC) • SL-701
    1year
    G-CSFR Is a Checkpoint of Natural Killer Cells Against Tumor (ASH 2023)
    "Cell Killing" and "leukocyte mediated cytotoxicity" pathway was enriched in CSF3R△NK/NK mice, indicating enhanced activation state of NK cells. In conclusion, our results uncover a potent checkpoint in NK cells protecting against tumors, suggesting a promising approach of targeting G-CSFR for NK cell-based immunotherapies.
    IO biomarker
    |
    CSF3R (Colony Stimulating Factor 3 Receptor) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    LAMP1 expression
    1year
    Jak2V617F Bone Marrow Exposure Leads to Dysfunction of Normal NK Cells (ASH 2023)
    Our findings demonstrated that leukemia exposure led to altered NK cell frequency and maturation distribution as demonstrated by reduced immature and an increased tolerant and cytotoxic fraction. Changes in the expression profile of activating and inhibitory receptors were also observed. Therefore, we concluded that the leukemic environment leads to NK dysfunction and that strategies that aim to control NK maturation and the interaction between stem cell ligands and functional NK receptors can be explored to restore immunosurveillance in JAK2V671F Myeloproliferative Neoplasms.
    IO biomarker
    |
    TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CD69 (CD69 Molecule) • CD27 (CD27 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1) • ITGAM (Integrin, alpha M) • KLRC1 (Killer Cell Lectin Like Receptor C1) • NKG2D (killer cell lectin like receptor K1)
    |
    JAK2 V617F • LAMP1 expression • TIGIT expression
    1year
    Human iPSC-Derived NK Cells with Knock-in of the BCL2 G101V Mutation Are Resistant to Venetoclax and Demonstrate Improved Anti-AML Activity In Vivo (ASH 2023)
    Together our results demonstrate that iPSC-NK cells can be engineered to generate venetoclax-resistance for use in combination with concurrent venetoclax therapy to markedly improve treatment of AML. Furthermore, this work demonstrates that novel drug resistance mechanisms can be introduced via genome engineering into iPSC-derived NK cells as a new strategy to produce improved cell products for "off-the-shelf" therapy.
    Preclinical • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    BCL2 G101V • LAMP1 expression
    |
    Venclexta (venetoclax)
    1year
    Mutant Natural Killer Cell Dysfunction Enables the Immune Escape of Premalignant MDS Cell Clones (ASH 2023)
    This study demonstrates that MDS driver mutations in CCUS NK cells induce immune dysfunction, thus enabling the expansion of malignant cells and thereby contributing to MDS onset. Our results suggest that immunotherapy with adoptive NK cell transfer could restore the anti-tumor immune response in patients with CCUS and may be an effective approach to arrest disease progression and prevent MDS onset.
    Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • DNMT3A (DNA methyltransferase 1) • CD8 (cluster of differentiation 8) • TET2 (Tet Methylcytosine Dioxygenase 2) • IFNG (Interferon, gamma) • CD34 (CD34 molecule) • NCAM1 (Neural cell adhesion molecule 1) • LAMP1 (Lysosomal Associated Membrane Protein 1) • GZMA (Granzyme A)
    |
    DNMT3A mutation • TET2 mutation • LAMP1 expression
    1year
    Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Truly Refractory Hodgkin Lymphoma Patients Is Highly Effective and Responses Are Mediated By NK Cells (ASH 2023)
    All patients received conventional 2nd line chemo followed by 3rd line chemo-immunotherapy with Brentuximab-Vedotin (BV) in non-responding patients. RHL patients in the treatment arm had an excellent outcome if compared to the control arm, which included patient who did respond to conventional treatment. Biological data suggests that this approach may accelerate NK cell development/maturation and suggest that NK cells may mediate response to CI in HL.
    Clinical • PD(L)-1 Biomarker • IO biomarker • Post-transplantation
    |
    PD-L2 (Programmed Cell Death 1 Ligand 2) • NCAM1 (Neural cell adhesion molecule 1) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    LAMP1 expression
    |
    Opdivo (nivolumab) • Adcetris (brentuximab vedotin)
    1year
    Pgam1 Regulate Adaptive NK Cells in Anti-Viral and Anti-Tumor Response (ASH 2023)
    In summary, our studies shown the glycolysis is effectively support the faster adaptive NK cells expansion and CMV response. PGAM1-mediated glycolysis is significant for NK cells anti-tumor and anti-viral function.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-1 (Programmed cell death 1) • IL2RA (Interleukin 2 receptor, alpha) • SYK (Spleen tyrosine kinase) • CD27 (CD27 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1) • HLA-E (Major Histocompatibility Complex, Class I, E) • ITGAM (Integrin, alpha M) • TGFB1 (Transforming Growth Factor Beta 1) • KLRC1 (Killer Cell Lectin Like Receptor C1) • KLRD1 (Killer Cell Lectin Like Receptor D1)
    |
    LAMP1 expression
    1year
    CD39 conventional CD4 T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade. (PubMed, Oncoimmunology)
    We found that high CD4 and ENTPD1 (CD39) gene expression in human tumor tissues correlated with a higher overall survival rate in breast cancer patients. Our results identify CD39 as a biomarker of Tconv cells, with characteristics of both exhaustion and cytotoxic potential, and indicate CD39 Tconv cells as players within the immune response against tumors.
    Journal • IO biomarker
    |
    CD4 (CD4 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1) • GZMB (Granzyme B) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • PRF1 (Perforin 1)
    |
    PD-1 expression • LAMP1 expression • CTLA4 expression • ENTPD1 expression
    1year
    Radiation Therapy Sensitizes Head-and-Neck Cancer Cells to Killing by Chimeric Antigen Receptor (CAR)-NK Cells Targeting CD70. (PubMed, Int J Radiat Oncol Biol Phys)
    This work represents the first preclinical study to identify the synergy of RT and CAR-NK cell therapy in solid tumors and is the first demonstration of CAR-NK cell activity against human HNSCCs. We show significantly enhanced potency of CAR-NK cells against irradiated tumor cells in vitro. Collectively, this research will be vital to guide efforts expanding into other target antigens and tumor types.
    Journal • IO biomarker
    |
    IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CD70 (CD70 Molecule) • CD27 (CD27 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    CD70 expression • IFNG expression • LAMP1 expression
    1year
    PIM2 kinase regulates TIGIT expression and energy metabolism in NK cells from multiple myeloma patients (IMW 2023)
    PIM2 kinase regulates NK cell anti-myeloma activity by modulating TIGIT expression and energy metabolism.
    Clinical • IO biomarker
    |
    IFNG (Interferon, gamma) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • LAMP1 (Lysosomal Associated Membrane Protein 1) • PVR (PVR Cell Adhesion Molecule) • ETS1 (ETS Proto-Oncogene 1)
    |
    IFNG expression • LAMP1 expression
    |
    Q-Force (quercetin)
    1year
    The bone marrow stroma influences extrinsic apoptotic signaling and results in resistance to BCMA CAR-T cell induced cell death (IMW 2023)
    These results demonstrate that the BMM can induce MM cell intrinsic protection against CAR-T therapy in part due to soluble stromal factors. This protection may be due in part to inhibition of the extrinsic apoptotic pathway. Stromal factors including IL6 inhibit rCD95L induced type 1 induced cell death through a reduction in Caspase 8 activity.
    CAR T-Cell Therapy • IO biomarker • Stroma
    |
    BCL2 (B-cell CLL/lymphoma 2) • LAMP1 (Lysosomal Associated Membrane Protein 1) • CASP8 (Caspase 8) • FAS (Fas cell surface death receptor) • ANXA5 (Annexin A5)
    |
    LAMP1 expression
    1year
    Combination of forimtamig with standard of care improves depth and duration of response in preclinical models of multiple myeloma (IMW 2023)
    Synergistic anti-tumoral and NK stimulatory effects suggest a benefit of daratumumab combination in patients with high tumor burden and high risk of developing CRS. Broad immunomodulatory effects of pomalidomide could help sustain T cell responses in patients but may increase the risk of CRS. Considering the importance of balancing CRS and efficacy, carfilzomib was identified as another promising combination partner for forimtamig.
    Preclinical • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • IL2RA (Interleukin 2 receptor, alpha) • CD69 (CD69 Molecule) • IL2 (Interleukin 2) • TNFRSF9 (TNF Receptor Superfamily Member 9) • LAMP1 (Lysosomal Associated Membrane Protein 1) • GZMA (Granzyme A) • CCL3 (C-C Motif Chemokine Ligand 3)
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    LAMP1 expression
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    Darzalex (daratumumab) • carfilzomib • pomalidomide • forimtamig (RG6234)
    1year
    LAMP1/2 as potential diagnostic and prognostic marker for brain lower grade glioma: A review. (PubMed, Medicine (Baltimore))
    lysosomal associated membrane protein 2 and LAMP5 were significantly down-regulated expression in samples of TP53 mutant in LGG compared to TP53 wild type. In addition, Lysosomal associated membrane protein 3 and LAMP4 were significantly overexpressed in samples of TP53 mutant in LGG Enrichment analysis applied to each component indicated that biological function was primarily associated with series of pathways in synapse and immunity.
    Review • Journal
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    TP53 (Tumor protein P53) • LAMP1 (Lysosomal Associated Membrane Protein 1) • LAMP3 (Lysosomal Associated Membrane Protein 3) • CD68 (CD68 Molecule) • LAMP2 (Lysosomal Associated Membrane Protein 2)
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    TP53 mutation • TP53 wild-type • LAMP1 expression • TP53 expression • LAMP3 expression
    1year
    Radiation Therapy Sensitizes Head-and-Neck Cancer Cells to Killing by Chimeric Antigen Receptor (CAR)-NK Cells Targeting CD70 (ASTRO 2023)
    This work represents the first preclinical study to identify the synergy of RT and CAR-NK cell therapy in solid tumors and is the first demonstration of CAR-NK cell activity against human HNSCCs. We show significantly enhanced potency of CAR-NK cells against irradiated tumor cells in vitro . Collectively, this research will be vital to guide efforts expanding into other target antigens and tumor types.
    IO biomarker
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    TNFA (Tumor Necrosis Factor-Alpha) • CD70 (CD70 Molecule) • CD27 (CD27 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1)
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    CD70 expression • LAMP1 expression
    over1year
    Evaluation of Fluoxetine and Cytotoxic Lysosomal Stress in Glioma (FLIRT) (clinicaltrials.gov)
    P1, N=30, Recruiting, Duke University | Not yet recruiting --> Recruiting
    Enrollment open
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    LAMP1 (Lysosomal Associated Membrane Protein 1)
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    LAMP1 expression • IDH wild-type
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    temozolomide • fluoxetine