ORCID Profile
0000-0002-5942-8592
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Publisher: Elsevier BV
Date: 06-2020
Publisher: Springer Science and Business Media LLC
Date: 18-05-2020
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481420.V1
Abstract: Supplementary Figure 7. No cytokine storm was observed in WAP- and MMTV-Her2 mice post the ACTIV+Pano treatment.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481417
Abstract: Supplementary Figure 8. Proposed mechanisms and clinical application for the ACTIV+Pano treatment.
Publisher: Wiley
Date: 2019
DOI: 10.1002/CTI2.1094
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481435
Abstract: Supplementary Figure 3. Pano induced pancreatic tumor cell apoptosis.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481438
Abstract: Supplementary Figure 2. Pancreatic cells are resistant to VV-gp100 oncolysis but sensitive to CAR T cell-mediated cytotoxicity.
Publisher: Frontiers Media SA
Date: 12-02-2019
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6530693
Abstract: AbstractPurpose: In this article, we describe a combination chimeric antigen receptor (CAR) T-cell therapy that eradicated the majority of tumors in two immunocompetent murine pancreatic cancer models and a human pancreatic cancer xenograft model. Experimental Design: We used a dual-specific murine CAR T cell that expresses a CAR against the Her2 tumor antigen, and a T-cell receptor (TCR) specific for gp100. As gp100 is also known as pMEL, the dual-specific CAR T cells are thus denoted as CARaMEL cells. A vaccine containing live vaccinia virus coding a gp100 minigene (VV-gp100) was administered to the recipient mice to stimulate CARaMEL cells. The treatment also included the histone deacetylase inhibitor panobinostat (Pano). Results: The combination treatment enabled significant suppression of Her2 sup + /sup pancreatic cancers leading to the eradication of the majority of the tumors. Besides inducing cancer cell apoptosis, Pano enhanced CAR T-cell gene accessibility and promoted CAR T-cell differentiation into central memory cells. To test the translational potential of this approach, we established a method to transduce human T cells with an anti-Her2 CAR and a gp100-TCR. The exposure of the human T cells to Pano promoted a T-cell central memory phenotype and the combination treatment of human CARaMEL cells and Pano eradicated human pancreatic cancer xenografts in mice. Conclusions: We propose that patients with pancreatic cancer could be treated using a scheme that contains dual-specific CAR T cells, a vaccine that activates the dual-specific CAR T cells through their TCR, and the administration of Pano. /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481441.V1
Abstract: Supplementary Figure 1. Panc02-Her2, KPC-Her2 and 24JK-Her2 cells express comparable levels of Her2.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481426.V1
Abstract: Supplementary Figure 5. Pano did not alter Her2 or H2-Db expression on Panc02-Her2 tumor cells in vivo and CARaMEL cells were detectable over 100 days in ACTIV+ Pano treated mice.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481441
Abstract: Supplementary Figure 1. Panc02-Her2, KPC-Her2 and 24JK-Her2 cells express comparable levels of Her2.
Publisher: Proceedings of the National Academy of Sciences
Date: 25-11-2019
Abstract: Regressions of some blood cancer can follow infusion of patients’ own T cells gene-modified to express a chimeric antigen receptor (CAR). These regressions are associated with extensive proliferation and engraftment of CAR T cells. However, for most common solid cancers, CAR T cells encounter antigen in a microenvironment that is immunosuppressive and lacking T cell support, and significant engraftment does not always occur. Here, we deliver enterotoxins or bispecific antibody to provide CAR T cells with support signals from antigen-presenting cells in lymphoid tissue, away from the tumor microenvironment. We demonstrate that this enables CAR T cell activation and proliferation, leading to enhanced responses against solid tumors in mice. This approach could lead to effective treatments for many common cancers.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481438.V1
Abstract: Supplementary Figure 2. Pancreatic cells are resistant to VV-gp100 oncolysis but sensitive to CAR T cell-mediated cytotoxicity.
Publisher: Wiley
Date: 2020
DOI: 10.1002/CTI2.1157
Publisher: American Association for Cancer Research (AACR)
Date: 02-09-2021
DOI: 10.1158/1078-0432.CCR-21-1141
Abstract: In this article, we describe a combination chimeric antigen receptor (CAR) T-cell therapy that eradicated the majority of tumors in two immunocompetent murine pancreatic cancer models and a human pancreatic cancer xenograft model. We used a dual-specific murine CAR T cell that expresses a CAR against the Her2 tumor antigen, and a T-cell receptor (TCR) specific for gp100. As gp100 is also known as pMEL, the dual-specific CAR T cells are thus denoted as CARaMEL cells. A vaccine containing live vaccinia virus coding a gp100 minigene (VV-gp100) was administered to the recipient mice to stimulate CARaMEL cells. The treatment also included the histone deacetylase inhibitor panobinostat (Pano). The combination treatment enabled significant suppression of Her2+ pancreatic cancers leading to the eradication of the majority of the tumors. Besides inducing cancer cell apoptosis, Pano enhanced CAR T-cell gene accessibility and promoted CAR T-cell differentiation into central memory cells. To test the translational potential of this approach, we established a method to transduce human T cells with an anti-Her2 CAR and a gp100-TCR. The exposure of the human T cells to Pano promoted a T-cell central memory phenotype and the combination treatment of human CARaMEL cells and Pano eradicated human pancreatic cancer xenografts in mice. We propose that patients with pancreatic cancer could be treated using a scheme that contains dual-specific CAR T cells, a vaccine that activates the dual-specific CAR T cells through their TCR, and the administration of Pano.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481417.V1
Abstract: Supplementary Figure 8. Proposed mechanisms and clinical application for the ACTIV+Pano treatment.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481429
Abstract: Supplementary Figure 4. Pano did not enhance the cytotoxicity of CARaMEL cells nor oncolysis of VV-gp100.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2021
DOI: 10.1038/S41577-021-00539-6
Abstract: The antitumour activity of endogenous or adoptively transferred tumour-specific T cells is highly dependent on their differentiation status. It is now apparent that less differentiated T cells compared with fully differentiated effector T cells have better antitumour therapeutic effects owing to their enhanced capacity to expand and their long-term persistence. In patients with cancer, the presence of endogenous or adoptively transferred T cells with stem-like memory or precursor phenotype correlates with improved therapeutic outcomes. Advances in our understanding of T cell differentiation states at the epigenetic and transcriptional levels have led to the development of novel methods to generate tumour-specific T cells - namely, chimeric antigen receptor T cells - that are more persistent and resistant to the development of dysfunction. These include the use of novel culture methods before infusion, modulation of transcriptional, metabolic and/or epigenetic programming, and strategies that fine-tune antigen receptor signalling. This Review discusses existing barriers and strategies to overcome them for successful T cell expansion and persistence in the context of adoptive T cell immunotherapy for solid cancers.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481423.V1
Abstract: Supplementary Figure 6. The infiltration of CD8+ cells to the Her2+ non-tumor regions.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6530693.V1
Abstract: AbstractPurpose: In this article, we describe a combination chimeric antigen receptor (CAR) T-cell therapy that eradicated the majority of tumors in two immunocompetent murine pancreatic cancer models and a human pancreatic cancer xenograft model. Experimental Design: We used a dual-specific murine CAR T cell that expresses a CAR against the Her2 tumor antigen, and a T-cell receptor (TCR) specific for gp100. As gp100 is also known as pMEL, the dual-specific CAR T cells are thus denoted as CARaMEL cells. A vaccine containing live vaccinia virus coding a gp100 minigene (VV-gp100) was administered to the recipient mice to stimulate CARaMEL cells. The treatment also included the histone deacetylase inhibitor panobinostat (Pano). Results: The combination treatment enabled significant suppression of Her2 sup + /sup pancreatic cancers leading to the eradication of the majority of the tumors. Besides inducing cancer cell apoptosis, Pano enhanced CAR T-cell gene accessibility and promoted CAR T-cell differentiation into central memory cells. To test the translational potential of this approach, we established a method to transduce human T cells with an anti-Her2 CAR and a gp100-TCR. The exposure of the human T cells to Pano promoted a T-cell central memory phenotype and the combination treatment of human CARaMEL cells and Pano eradicated human pancreatic cancer xenografts in mice. Conclusions: We propose that patients with pancreatic cancer could be treated using a scheme that contains dual-specific CAR T cells, a vaccine that activates the dual-specific CAR T cells through their TCR, and the administration of Pano. /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481426
Abstract: Supplementary Figure 5. Pano did not alter Her2 or H2-Db expression on Panc02-Her2 tumor cells in vivo and CARaMEL cells were detectable over 100 days in ACTIV+ Pano treated mice.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481420
Abstract: Supplementary Figure 7. No cytokine storm was observed in WAP- and MMTV-Her2 mice post the ACTIV+Pano treatment.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481423
Abstract: Supplementary Figure 6. The infiltration of CD8+ cells to the Her2+ non-tumor regions.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481429.V1
Abstract: Supplementary Figure 4. Pano did not enhance the cytotoxicity of CARaMEL cells nor oncolysis of VV-gp100.
Publisher: AME Publishing Company
Date: 08-2020
Publisher: Springer Science and Business Media LLC
Date: 06-08-2021
DOI: 10.1038/S41467-021-25009-4
Abstract: The function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor s les reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumor immunity in B16F10 and E0771 mouse tumor models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFN-γ-dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumor s les. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, and suggest a potential therapeutic avenue for cancer treatment.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481435.V1
Abstract: Supplementary Figure 3. Pano induced pancreatic tumor cell apoptosis.
No related grants have been discovered for Jack Chan.