CAR8 failure in an OT1 TCR transgenic T cell after exposure to OVA

Slides:

Advertisements

Similar presentations

T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia by Michael Kalos, Bruce.

Advertisements

Fig. 1. TP is highly expressed in myeloma.

Fig. 6. Transgenic expression of αLNNd and mag in dyW/dyW mice improves muscle function, increases body weight, and prolongs life span. Transgenic expression.

Fig. 5. Correlation between CD34+CD45RA−CD90+ cell dose, engraftment success, and onset of neutrophil/platelet recovery in nonhuman primates. Correlation.

Transfer of miR-223 during neutrophil-epithelial cell interactions

Fig. 2. Mechanism of PD-L1 down-regulation in NOD HSPCs.

Fig. 2. VEGF-C/VEGFR-3 signaling increases responsiveness of melanoma to immunotherapy. VEGF-C/VEGFR-3 signaling increases responsiveness of melanoma to.

Fig. 1 Increasing UCB cell dose impairs short-term progenitor cell engraftment. Increasing UCB cell dose impairs short-term progenitor cell engraftment.

In vivo responses of AMLMLL to ATRi.

Fig. 4. Biomechanical properties of treated tibiae.

Fig. 8. In vivo suppression of MM by CMLD

Fig. 2 Maraba treatment results in complete responses in the window of opportunity setting. Maraba treatment results in complete responses in the window.

Fig. 6. Increased efficacy of immunotherapy in lymphangiogenic B16 melanomas depends on CCR7 signaling before therapy and local activation and expansion.

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. 4 Topical application of SAAP-148 ointment eradicates acute and established infections of MRSA and A. baumannii from the skin. Topical application.

Maraba treatment sensitizes 4T1 tumors to immune checkpoint blockade

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. 5. Antitumor efficacy of ERY974 in immunocompetent human CD3 transgenic mice. Antitumor efficacy of ERY974 in immunocompetent human CD3 transgenic.

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,

Dual enhancement of T and NK cell function by pulsatile inhibition of SHIP1 improves antitumor immunity and survival by Matthew Gumbleton, Raki Sudan,

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

Fig. 7 Gel scaffold for inhibition of postsurgical recurrence of B16F10 tumors. Gel scaffold for inhibition of postsurgical recurrence of B16F10 tumors.

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

Fig. 5. Serum VEGF-C correlates with antitumor immune responses and PFS after immunotherapy in human metastatic melanoma patients. Serum VEGF-C correlates.

Fig. 2 L. lactis–derived lactic acid antagonizes V

Fig. 6. Apoptotic MSCs exert in vivo immunosuppression in a TH2-type inflammation model in the absence of cytotoxic cells. Apoptotic MSCs exert in vivo.

Persistence of CAR4 cells is reduced after sustained TCR engagement

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.

Fig. 5. pKL cells abrogate the autoimmune response in vitro.

Fig. 7. ApoMSCs exert immunosuppressive activity in GvHD and elicit IDO in engulfing recipient phagocytes. ApoMSCs exert immunosuppressive activity in.

Fig. 8 Combining M7824 with radiation or chemotherapy enhances antitumor efficacy. Combining M7824 with radiation or chemotherapy enhances antitumor efficacy.

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. 4. Improved tumor response to docetaxel in TNBC and trastuzumab in HER2-amplified PDX models with the addition of S Improved tumor response.

Fig. 4. Loss of DLK expression is neuroprotective in the SOD1G93A mouse model of ALS. Loss of DLK expression is neuroprotective in the SOD1G93A mouse model.

Comparison of therapeutic efficacies of C12G6 and other bnAbs in mice

Fig. 6. pKL cells revert hyperglycemia in NOD mice in vivo.

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

Fig. 6 Anticancer effects in PyMT-MMTV syngeneic and MDA-MB-231 xenograft-bearing mice. Anticancer effects in PyMT-MMTV syngeneic and MDA-MB-231 xenograft-bearing.

Fig. 3. VEGFR-3 signaling increases infiltration of naïve T cells in a CCR7-dependent manner. VEGFR-3 signaling increases infiltration of naïve T cells.

Fig. 2. Exposure of both TCR and CAR antigens diminishes efficacy of CAR8 but not CAR4 cells. Exposure of both TCR and CAR antigens diminishes efficacy.

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

Evaluation of clinical responses after infusion of CART19 cells

Fig. 4. Local application of FR provides prolonged protection against Gq-dependent airway constriction in normal and OVA-sensitized mice in vivo. Local.

Fig. 5 ALRN-6924 shows robust antileukemic activity in primary AML cells and in vivo. ALRN-6924 shows robust antileukemic activity in primary AML cells.

Arp2/3-mediated formation of nuclear actin networks is essential for CD4+ T cell effector functions. Arp2/3-mediated formation of nuclear actin networks.

Fig. 3 Activation of freshly isolated CD4+ T cells from HIV-infected patients on ART selectively reverses baseline blocks to splicing, elongation, and.

Jennifer K. Broom, Andrew M. Lew, Hiroaki Azukizawa, Tony J

Fig. 5 Early and modest immune response at day 3 after exposure in Delayed animals. Early and modest immune response at day 3 after exposure in Delayed.

Fig. 6. Eradication of FLT3-ITD+ AML cells in vivo through combined inhibition of kinase and antiapoptotic pathways. Eradication of FLT3-ITD+ AML cells.

Fig. 2. Increased CD19 CAR-T cell expansion and persistence after Cy/Flu lymphodepletion. Increased CD19 CAR-T cell expansion and persistence after Cy/Flu.

Fig. 8. Zbtb7a deficiency impairs antigen presentation by AMs.

Fig. 1. MSCs undergo in vivo apoptosis after infusion without affecting immunosuppression. MSCs undergo in vivo apoptosis after infusion without affecting.

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.

Fig. 8 Combining M7824 with radiation or chemotherapy enhances antitumor efficacy. Combining M7824 with radiation or chemotherapy enhances antitumor efficacy.

Fig. 3. Improved clinical responses to CD19 CAR-T cell immunotherapy after Cy/Flu lymphodepletion. Improved clinical responses to CD19 CAR-T cell immunotherapy.

Fig. 3. Increased expression of exhaustion markers and apoptosis markers on CAR8 cells in the presence of TCR antigen. Increased expression of exhaustion.

Fig. 1. CAR4 and CAR8 cells demonstrate in vitro and in vivo antileukemic efficacy. CAR4 and CAR8 cells demonstrate in vitro and in vivo antileukemic efficacy.

The selective depletion of DTR-expressing FAP+/CD45+ and FAP+/CD45− tumoral cells from bone marrow chimeric mice by the administration of DTX. A, sketch.

Fig. 2 Extended local release of agonists of innate immunity prevents tumor recurrence and eliminates distal metastases. Extended local release of agonists.

Fig. 2. PlGF-2123–144 conjugation reduces systemic exposure to checkpoint blockade Abs and potential treatment-related toxicity. PlGF-2123–144 conjugation.

Enhanced antitumor effects with combination IL21 and anti–PD-1/anti–Tim-3 therapy. Enhanced antitumor effects with combination IL21 and anti–PD-1/anti–Tim-3.

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.

Varying the MHC-I affinity, TCR affinity or antigen dose alters the phenotype of CD8 T cells ex vivo. Varying the MHC-I affinity, TCR affinity or antigen.

Kaplan–Meier curves of relapse-free survival of the CAR-T cohort (left) and the HCT cohort (right) of 8 CAR-T patients and 12 HCT patients whose preceding.

Fig. 2. In vivo local CD25-targeted NIR-PIT induces regression of treated LL/2-luc tumors. In vivo local CD25-targeted NIR-PIT induces regression of treated.

Presentation transcript:

Fig. 5. CAR8 failure in an OT1 TCR transgenic T cell after exposure to OVA. CAR8 failure in an OT1 TCR transgenic T cell after exposure to OVA. (A) CD107a expression on OT1-CAR T cells generated from Rag1−/− OT1 spleens at 4 hours of coincubation with E2aPbx expressing CD19 and/or OVA antigens. Iso cntrl, isotype control. (B) Percent viable E2aPbx cells expressing varying combinations of the CD19 and OVA antigens after 3 days of coculture with OT1-CAR or mock-OT1 T cells. (C) OVA-expressing hematopoietic chimeras were generated by CD3-depleted bone marrow transplant 21 days before inoculation with 1 × 106 E2aPbx, with lymphodepletion and 1 × 106 CD19 OT1-CAR8 cell treatment on day 0. (D) Survival of OVA chimeric mice treated with OT1-CAR8 T cells. (E) Leukemia burden of OT1-CAR8–treated mice 7 days after infusion. BM, bone marrow. (F and G) Analysis of infused OT1-CAR8 cells from the bone marrow 7 days after infusion. (F) PD-1 expression and (G) LAG3 expression on OT1-CAR8 cell [for (E) to (G): *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, relative to the WT→WT group, one-way ANOVA performed for all comparisons and log-rank Mantel-Cox test for survival analysis]. Yinmeng Yang et al., Sci Transl Med 2017;9:eaag1209 Published by AAAS