Selection of a 4-1BB-endodomain–based anti-EGFRvIII CAR construct

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Volume 17, Issue 9, Pages (September 2009)

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Volume 25, Issue 10, Pages (October 2017)

by Rafijul Bari, Teresa Bell, Wai-Hang Leung, Queenie P

Fig. 2. LUM015 fluorescently labels tumor cells in mouse models of STS and breast cancer. LUM015 fluorescently labels tumor cells in mouse models of STS.

Fig. 1. Potent and selective down-regulation of KRAS mRNA and protein by AZD4785 in vitro and in vivo. Potent and selective down-regulation of KRAS mRNA.

Fig. 4. Intramuscular injection of AAV9-Cas9/sgRNA-51 corrects dystrophin expression. Intramuscular injection of AAV9-Cas9/sgRNA-51 corrects dystrophin.

Fig. 2. Engraftment of CART-EGFRvIII and cytokine modulation in the peripheral blood. Engraftment of CART-EGFRvIII and cytokine modulation in the peripheral.

Fig. 1 Localized treatment of TNBC cancers kills tumor cells and minimizes the metastatic burden. Localized treatment of TNBC cancers kills tumor cells.

Fig. 8. In vivo suppression of MM by CMLD

PVSRIPO-mediated APC activation occurs in immunosuppressive conditions

Fig. 8. mRIPO elicits neutrophil influx followed by DC and T cell infiltration into tumors. mRIPO elicits neutrophil influx followed by DC and T cell infiltration.

Fig. 1 ZIKV-related flaviviruses cause fetal demise in mice that can be prevented by mAb treatment. ZIKV-related flaviviruses cause fetal demise in mice.

Fig. 2. GPC3 expression in normal and tumor tissues.

Fig. 4. The effects of AVP or d(Leu4Lys8)VP, a specific AVPR1B agonist, on anemic rodents. The effects of AVP or d(Leu4Lys8)VP, a specific AVPR1B agonist,

Fig. 5. Immunohistochemistry of the tumor microenvironment in GBM specimens before and after CART-EGFRvIII infusion. Immunohistochemistry of the tumor.

Fig. 6. PVSRIPO oncolysate–pulsed DCs generate tumor antigen–specific CTL immunity in vitro. PVSRIPO oncolysate–pulsed DCs generate tumor antigen–specific.

Fig. 5. Pharmacological JAK2 inhibition in vivo abrogates tumor-initiating potential after chemotherapy. Pharmacological JAK2 inhibition in vivo abrogates.

Fig. 5 A competent Fc is required for the antitumor immune response.

Fig. 4 Expression of cleaved caspase 3, PD-L1, and PD-1 in HGGs after reovirus treatment. Expression of cleaved caspase 3, PD-L1, and PD-1 in HGGs after.

Fig. 4. Antitumor efficacy of ERY974 against various cancer types.

Fig. 5 Combination intravenous reovirus and checkpoint inhibition in an orthotopic syngeneic brain tumor model. Combination intravenous reovirus and checkpoint.

PD‐L1 silencing in antigen presenting DCs results in hyperactivated pro‐inflammatory TCRhigh CD8+ T cells. PD‐L1 silencing in antigen presenting DCs results.

Fig. 5 Hypoxic tumors from obese mice associate with increased production of IL-6 by adipocytes and myeloid cells. Hypoxic tumors from obese mice associate.

Fig. 3 In situ vaccination with CpG and anti-OX40 is therapeutic in a spontaneous tumor model. In situ vaccination with CpG and anti-OX40 is therapeutic.

Fig. 4. BET inhibition sensitizes HR-proficient tumors to PARPi treatment in vivo. BET inhibition sensitizes HR-proficient tumors to PARPi treatment in.

Fig. 4. Restriction of TCR antigen to hematopoietic tissues does not prevent CAR8 exhaustion and failure of leukemia clearance. Restriction of TCR antigen.

Fig. 7 BRD0705 impairs colony formation in AML cell lines and patient cells and shows in vivo efficacy in multiple AML mouse models. BRD0705 impairs colony.

Fig. 4 DMF enhances VSVΔ51 therapeutic efficacy in syngeneic and xenograft tumor models. DMF enhances VSVΔ51 therapeutic efficacy in syngeneic and xenograft.

Fig. 7. KIF11 informs patient prognosis, and targeting improves survival in a preclinical model. KIF11 informs patient prognosis, and targeting improves.

by Kalpana Parvathaneni, and David W. Scott

Role of immune and inflammatory cells in lung cancer–associated PH

Fig. 5 Local gel scaffold for T cell memory response.

Fig. 3 M7824 inhibits tumor growth and metastasis and provides long-term antitumor immunity. M7824 inhibits tumor growth and metastasis and provides long-term.

Fig. 1. PGBD5-expressing cells do not tolerate deficiency of nonhomologous end-joining DNA repair. PGBD5-expressing cells do not tolerate deficiency of.

Fig. 1 CpG induces the expression of OX40 on CD4 T cells.

Fig. 7 DMN-Tre labeling of Mycobacterium tuberculosis is inhibited by tuberculosis drug cocktail, unlike auramine staining. DMN-Tre labeling of Mycobacterium.

Fig. 4 PD-L1 expression is found in the spleen and the BM of mice transplanted with JAK2V617F-transduced bone marrow. PD-L1 expression is found in the.

Fig. 1 Effect of preinfection β7Hi CD45RA−CD4+ T cell frequency on HIV acquisition risk in CAPRISA 004 study. Effect of preinfection β7Hi CD45RA−CD4+ T.

Fig. 7. mRIPO therapy restricts tumor growth and produces antigen-specific antitumor immunity. mRIPO therapy restricts tumor growth and produces antigen-specific.

Fig. 2. IL-2/rapamycin–expanded T cells express homing receptors to traffic to lymphoma sites and are resistant to SN-38 toxicity. IL-2/rapamycin–expanded.

Fig. 3. TKI sensitivity assessed by the MANO method.

CD facilitates RCT in vivo and promotes urinary cholesterol excretion

Fig. 3 Agonists of innate immunity are effective only when released locally from the hydrogel. Agonists of innate immunity are effective only when released.

Fig. 4 Surgery initiates a systemic inflammatory response that triggers the outgrowth of distant immunogenic tumors and can be inhibited by perioperative.

Bexarotene is neuroprotective in mouse and human HD neurons in vitro

Fig. 6 Innate and adaptive immunity, but not ADCC, contributes to M7824 antitumor activity. Innate and adaptive immunity, but not ADCC, contributes to.

Fig. 4. Dabrafenib and trametinib changed the cellular components of the tumor microenvironment. Dabrafenib and trametinib changed the cellular components.

Fig. 3 CSF1 is expressed in human melanoma.

Molecular Therapy - Oncolytics

Fig. 5 DMN-Tre labeling is selective for live mycobacteria.

Fig. 5 Extended local release of R848 increases the number of innate and adaptive antitumor immune cells and cytokines. Extended local release of R848.

JAK2 knockdown abrogates tumorsphere expansion after chemotherapy

CSF1 secretion by melanoma cells is induced by CTL-derived cytokines

Fig. 4. Clearance of 12-mer-1 from a nonhuman primate model.

CAR T‐cell generation in human PBMC‐transplanted mice

Integrin binding of soluble GRGDSP and fibronectin.

Fig. 5 A competent Fc is required for the antitumor immune response.

Fig. 2 CD19 CAR T cells expressing tPSMA maintain function in vitro and in vivo. CD19 CAR T cells expressing tPSMA maintain function in vitro and in vivo.

Fig. 3 NK cells are enriched in ICB-sensitive tumors in mouse models and patients and are required for response. NK cells are enriched in ICB-sensitive.

Single-Shot, Multicycle Suicide Gene Therapy by Replication-Competent Retrovirus Vectors Achieves Long-Term Survival Benefit in Experimental Glioma Chien-Kuo.

Colonization in tumor models and different modes of administration

Fig. 1. Potent and selective down-regulation of KRAS mRNA and protein by AZD4785 in vitro and in vivo. Potent and selective down-regulation of KRAS mRNA.

Fig. 5. Immunohistochemistry of the tumor microenvironment in GBM specimens before and after CART-EGFRvIII infusion. Immunohistochemistry of the tumor.

Fig. 3 BMS blocks functional responses in primary immune cells driven by IL-23 and IL-12. BMS blocks functional responses in primary immune.

Fig. 2 In situ vaccination of CpG in combination with anti-OX40 antibody cures established local and distant tumors. In situ vaccination of CpG in combination.

Rational development and characterization of humanized anti–EGFR variant III chimeric antigen receptor T cells for glioblastoma by Laura A. Johnson, John.

Fig. 2. LUM015 fluorescently labels tumor cells in mouse models of STS and breast cancer. LUM015 fluorescently labels tumor cells in mouse models of STS.

Protracted temozolomide (TMZ) treatment leads to acquired TMZ resistance in glioblastoma (GBM) cells in vivo. Protracted temozolomide (TMZ) treatment leads.

GPR55 regulates γδT cell egress from PP and homing of gut-tropic CD8 T cells to the small intestine. GPR55 regulates γδT cell egress from PP and homing.

Fig. 3 Superiority of BAFF-R versus CD19-CAR T cells in a Burkitt lymphoma model is not due to greater tumor antigen density. Superiority of BAFF-R versus.

Presentation transcript:

Fig. 1. Selection of a 4-1BB-endodomain–based anti-EGFRvIII CAR construct. Selection of a 4-1BB-endodomain–based anti-EGFRvIII CAR construct.(A) Vector maps of tested anti-EGFRvIII CAR designs. (B) Flow-based cytotoxicity of CART-EGFRvIII cells against EGFRvIII+ glioma cell line. The glioblastoma cell line U87MG was stably transduced with EGFRvIII, fluorescently labeled with CFSE, and cocultured for 18 hours. Untransduced (UTD) or CD19.BBz CAR T cells were used as negative controls and compared to 3C10.BBz, 3C10.28BBz, or 139.BBz EGFRvIII CAR T cells. Lysis of parental cells (U87MG) and EGFRvIII-transduced U87 cells was analyzed at different effector/target (E:T) ratios by flow cytometry. One representative experiment is shown. Samples were performed in duplicate in two replicative experiments. (C) CART-EGFRvIII cells eradicate glioblastoma in an orthotopic xenogeneic mouse model. Seven days after 5 × 104 U87-EGFRvIII cells were orthotopically implanted into mouse brains, mice were injected intravenously with either phosphate-buffered saline (PBS) alone, temozolomide (TMZ) alone, or temozolomide with 1 × 106 transduced T cells expressing the indicated CAR constructs. Tumor burden was quantified as total flux in units of photons/second. Bars indicate means ± SD (n = 10 mice per group). Note that all mice in the PBS group died by day 15. Laura A. Johnson et al., Sci Transl Med 2015;7:275ra22 Published by AAAS