In vivo efficacy of JAK inhibition in transformed Pax5+/− pro-B cells harboring Jak3V670A. In vivo efficacy of JAK inhibition in transformed Pax5+/− pro-B.

Slides:

Advertisements

Similar presentations

Influence of Donor Microbiota on the Severity of Experimental Graft-versus-Host- Disease Isao Tawara, Chen Liu, Hiroya Tamaki, Tomomi Toubai, Yaping Sun,

Advertisements

Continuous in vivo infusion of interferon-gamma (IFN-γ) enhances engraftment of syngeneic wild-type cells in Fanca–/– and Fancg–/– mice by Yue Si, Samantha.

Revealing lymphoma growth and the efficacy of immune cell therapies using in vivo bioluminescence imaging by Matthias Edinger, Yu-An Cao, Michael R. Verneris,

Effects of senescent cells on activity.

Efficacy of JAK/STAT pathway inhibition in murine xenograft models of early T-cell precursor (ETP) acute lymphoblastic leukemia by Shannon L. Maude, Sibasish.

TLR5 signaling in murine bone marrow induces hematopoietic progenitor cell proliferation and aids survival from radiation by Benyue Zhang, Damilola Oyewole-Said,

Effects of AG-221 treatment on survival and cell differentiation in an IDH2R140Q primary human AML xenograft model. Effects of AG-221 treatment on survival.

EPHB4 is a therapeutic target in AML and promotes leukemia cell survival via AKT by Akil A. Merchant, Aparna Jorapur, Amy McManus, Ren Liu, Valery Krasnoperov,

Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease by Tangsheng Yi, Dongchang Zhao, Chia-Lei.

The PI3K–Akt pathway is essential for the in vivo maintenance of murine Tregs. The PI3K–Akt pathway is essential for the in vivo maintenance of murine.

A Theranostic “SMART” Aptamer for Targeted Therapy of Prostate Cancer

Dynamic Change and Impact of Myeloid-Derived Suppressor Cells in Allogeneic Bone Marrow Transplantation in Mice Dapeng Wang, Yu Yu, Kelley Haarberg,

FGF-2 signaling mediates expansion of HSPCs

Mouse acute leukemia develops independent of self-renewal and differentiation potentials in hematopoietic stem and progenitor cells by Fang Dong, Haitao.

LV activation of DCs and subsequent CD8+ T cell priming are dependent on STING and cGAS but not on MyD88, TRIF, or MAVS. LV activation of DCs and subsequent.

Oncogenic role and therapeutic targeting of ABL-class and JAK-STAT activating kinase alterations in Ph-like ALL by Kathryn G. Roberts, Yung-Li Yang, Debbie.

CXCR5 expression accelerates Eμ-Tcl1 leukemogenesis and is indispensable for tumor cell recruitment to lymphoid B-cell follicles. CXCR5 expression accelerates.

MI-773 reduces the fraction of CSCs and prevents recurrence in ACC xenograft tumors. MI-773 reduces the fraction of CSCs and prevents recurrence in ACC.

Therapy model: CD34+CD33Del cells resist CD33-targeted immunotherapy.

Rab27a promotes migration of neutrophils in vivo and in vitro.

by Pamela J. Sung, Mayumi Sugita, Holly Koblish, Alexander E

Fig. 4. The effect of combined inhibition of BCL-2 and BCR-ABL on leukemia LT-HSC frequency. The effect of combined inhibition of BCL-2 and BCR-ABL on.

Ablation of PD-L1 in edited T3 sarcoma cells leads to augmented growth inhibition in WT mice. Ablation of PD-L1 in edited T3 sarcoma cells leads to augmented.

NOX1-deficient mice do not respond to GKT771 and exhibit reduced B16-F10 tumor growth associated with decreased production of angiogenic factors and minor.

RAPTOR deficiency impairs the DN-to-DP transition in αβ T cell development. RAPTOR deficiency impairs the DN-to-DP transition in αβ T cell development.

MRP2 inhibition mitigates pulmonary burden and bacteremia following lung challenge with S. pneumoniae. MRP2 inhibition mitigates pulmonary burden and bacteremia.

CD8 T cells play a critical role in responses of TILs due to BRAF inhibition. CD8 T cells play a critical role in responses of TILs due to BRAF inhibition.

Leukemic blasts express a “hypoxia signature

GS87 demonstrates efficacy in a circulating AML mouse model system.

coTCRcys-transduced T cells control tumor growth in vivo.

mTORC1 is required for malignant transformation in the Eμ-Myc model.

PRIMA-1Met inhibits the growth of multiple myeloma tumors with mutant p53 in vivo. PRIMA-1Met inhibits the growth of multiple myeloma tumors with mutant.

Response of the Idh2R140Q Flt3ITD leukemia model to AG-221 therapy.

Matriptase-2 inhibited breast tumor development in vivo.

Increase in proliferation and activation of immune cells in peripheral blood after NKTR-214 treatment. Increase in proliferation and activation of immune.

Paclitaxel treatment along with CXCR2 knockdown reduces tumor growth and metastasis. Paclitaxel treatment along with CXCR2 knockdown reduces tumor growth.

In vivo AraC treatment does not induce any consistent changes in CD34+/−CD38+/− phenotypes nor in quiescent leukemic cells but increases apoptotic cell.

Uptake of TEX by DCs in vivo.

ESKM is superior to ESK1 in vivo, and is effective against multiple tumor models. ESKM is superior to ESK1 in vivo, and is effective against multiple tumor.

M-CSFR inhibition decreases tumor-associated macrophages in mesothelioma and improves the DC therapy induced CD8+ T-cell phenotype. M-CSFR inhibition decreases.

Efficacy of DC therapy is synergistically enhanced by combination therapy with TAM depletion in mesothelioma mouse models. Efficacy of DC therapy is synergistically.

SY-1425 induces maturation in RARA-high AML

WP1066 inhibits the progression of OCIM2 cells through the cell cycle.

Fig. 6 Antitumor effect on tumor growth and pulmonary metastasis of CSSD-9 in vivo. Antitumor effect on tumor growth and pulmonary metastasis of CSSD-9.

The CD8+ cytotoxic T-cell response in Ron TK−/− hosts in response to tumors is necessary and sufficient to block metastasis. The CD8+ cytotoxic T-cell.

Systemic reovirus treatment targets disseminated human myeloma in vivo

Mice treated with DC therapy and/or M-CSFR inhibition were protected from tumor rechallenge with combination therapy-treated mice displaying superior recall.

YH25448 less suppresses WT EGFR than osimertinib in vivo.

Response of Tet2−/− Flt3ITD leukemia model to 5-Aza therapy.

Comparison of in vivo activity of 4D5scFvZZ and 4D5scFv.

TCR stimulation by agonistic mAb in vivo administration inhibits mouse T-ALL development. TCR stimulation by agonistic mAb in vivo administration inhibits.

Anti-CD40 activates TAMs and recruits inflammatory monocytes.

TAE-684 effectively inhibits the growth of H3122 in vivo.

Combination of R848 and anti-CD200R affects activation of tumor-infiltrating myeloid cells. Combination of R848 and anti-CD200R affects activation of tumor-infiltrating.

Effect of MZ treatment on lung colony formation in an experimental metastasis. Effect of MZ treatment on lung colony formation in an experimental metastasis.

Proliferation of TA3-Ha and TA3-St cells in vitro and in vivo.

Constitutive expression of JAK3M511I and HOXA9 leads to development of both AML and T-ALL in vivo. Constitutive expression of JAK3M511I and HOXA9 leads.

Loss of polarity gene Dlg1 leads to an expansion of C'-1 stage cells during pre-B cell differentiation. Loss of polarity gene Dlg1 leads to an expansion.

Preclinical trials in mouse models of APL

Induction of PD-1 in B cells by TLR agonists and primary HCC-SN.

Effect of HDC on the ROS production in mouse lungs after melanoma cell inoculation. Effect of HDC on the ROS production in mouse lungs after melanoma cell.

In vivo inhibition of IL-17 abrogates tumor-promoting effect of myeloid cells. In vivo inhibition of IL-17 abrogates tumor-promoting effect of myeloid.

Curative effect of W+T treatment in vivo.

B-cell development in young Pax5+/− mice.

ARQ 531 improves survival in the Eμ-TCL1 engraftment model compared with ibrutinib. ARQ 531 improves survival in the Eμ-TCL1 engraftment model compared.

MDSC population in patient peripheral blood.

T cells expressing a KIR-CAR/Dap12 show potent in vivo antitumor activity that is resistant to the tumor-induced T-cell hypofunction observed with CD3ζ-based.

Ezh2 inactivation inhibits initiation/progression of CML and establishment of secondary leukemia from existing LICs. A, protocol for induction of Ezh2.

Inhibition of MCL1 reduces AML in an in vivo murine model.

Parthenolide inhibits tumor promotion and increases p21 expression in vivo. Parthenolide inhibits tumor promotion and increases p21 expression in vivo.

Presentation transcript:

In vivo efficacy of JAK inhibition in transformed Pax5+/− pro-B cells harboring Jak3V670A. In vivo efficacy of JAK inhibition in transformed Pax5+/− pro-B cells harboring Jak3V670A. A, experimental setup. A total of 100,000 leukemic Pax5+/− pro-B cells harboring Jak3V670A mutation were injected into sublethally irradiated WT syngeneic mice. Regular bleedings were performed in order to check the development of the pB-ALL. When pB-ALL cells (B220loIgM−) were detected in the PB, the mouse treatment with ruxolitinib started. Mice were treated with ruxolitinib for only 5 days. FACS analysis of the PB was used to verify disease remission after therapy. B, percentage of PB pB-ALL cells (B220loIgM−) was monitored by flow cytometry at different time points in mice treated with ruxolitinib (ruxo). C, follow-up of leukemic cells (B220loIgM−) by PB flow cytometry in mice before and after ruxolitinib treatment. Mice treated with ruxolitinib showed a transient decrease in the blast cells except in mouse D009, which was alive and healthy 33 days after discontinuation of treatment. D, representative disseminated leukemia documented by FACS analysis of the BM of mice 5 days after starting treatment with ruxolitinib. Alberto Martín-Lorenzo et al. Cancer Discov 2015;5:1328-1343 ©2015 by American Association for Cancer Research