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Adoptive T cell therapy

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https://www.readbyqxmd.com/read/28445940/suppression-of-allograft-rejection-by-cd8-cd122-pd-1-tregs-is-dictated-by-their-fas-ligand-initiated-killing-of-effector-t-cells-versus-fas-mediated-own-apoptosis
#1
Huazhen Liu, Yeshu Wang, Qiaohuang Zeng, Yu-Qun Zeng, Chun-Ling Liang, Feifei Qiu, Hong Nie, Zhenhua Dai
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445461/tumour-ischaemia-by-interferon-%C3%AE-resembles-physiological-blood-vessel-regression
#2
Thomas Kammertoens, Christian Friese, Ainhoa Arina, Christian Idel, Dana Briesemeister, Michael Rothe, Andranik Ivanov, Anna Szymborska, Giannino Patone, Severine Kunz, Daniel Sommermeyer, Boris Engels, Matthias Leisegang, Ana Textor, Hans Joerg Fehling, Marcus Fruttiger, Michael Lohoff, Andreas Herrmann, Hua Yu, Ralph Weichselbaum, Wolfgang Uckert, Norbert Hübner, Holger Gerhardt, Dieter Beule, Hans Schreiber, Thomas Blankenstein
The relative contribution of the effector molecules produced by T cells to tumour rejection is unclear, but interferon-γ (IFNγ) is critical in most of the analysed models. Although IFNγ can impede tumour growth by acting directly on cancer cells, it must also act on the tumour stroma for effective rejection of large, established tumours. However, which stroma cells respond to IFNγ and by which mechanism IFNγ contributes to tumour rejection through stromal targeting have remained unknown. Here we use a model of IFNγ induction and an IFNγ-GFP fusion protein in large, vascularized tumours growing in mice that express the IFNγ receptor exclusively in defined cell types...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28443091/natural-killer-group-2d-ligand-depletion-reconstitutes-natural-killer-cell-immunosurveillance-of-head-and-neck-squamous-cell-carcinoma
#3
Sandra Weil, Stefanie Memmer, Axel Lechner, Volker Huppert, Ariane Giannattasio, Tamara Becker, Andreas Müller-Runte, Karen Lampe, Dirk Beutner, Alexander Quaas, Ralf Schubert, Eva Herrmann, Alexander Steinle, Ulrike Koehl, Lutz Walter, Michael S von Bergwelt-Baildon, Joachim Koch
Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive tumor originating from the epithelial lining of the upper aero-digestive tract accounting for 300,000 annual deaths worldwide due to failure of current therapies. The natural killer group 2D (NKG2D) receptors on natural killer (NK) cells and several T cell subsets play an important role for immunosurveillance of HNSCC and are thus targeted by tumor immune evasion strategies in particular by shedding of various NKG2D ligands (NKG2DLs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28436934/biopolymers-codelivering-engineered-t-cells-and-sting-agonists-can-eliminate-heterogeneous-tumors
#4
Tyrel T Smith, Howell F Moffett, Sirkka B Stephan, Cary F Opel, Amy G Dumigan, Xiuyun Jiang, Venu G Pillarisetty, Smitha P S Pillai, K Dane Wittrup, Matthias T Stephan
Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28434148/advancing-chimeric-antigen-receptor-t-cell-therapy-with-crispr-cas9
#5
REVIEW
Jiangtao Ren, Yangbing Zhao
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (CRISPR/Cas9) system, an RNA-guided DNA targeting technology, is triggering a revolution in the field of biology. CRISPR/Cas9 has demonstrated great potential for genetic manipulation. In this review, we discuss the current development of CRISPR/Cas9 technologies for therapeutic applications, especially chimeric antigen receptor (CAR) T cell-based adoptive immunotherapy. Different methods used to facilitate efficient CRISPR delivery and gene editing in T cells are compared...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28432067/adoptive-t-cell-therapy-has-antitumor-activity-in-uveal-melanoma
#6
(no author information available yet)
Adoptive T-cell therapy achieved responses in 35% of patients with metastatic uveal melanoma.
April 21, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28432065/adoptive-t-cell-transfer-targets-viral-and-nonviral-tumor-antigens
#7
(no author information available yet)
Successful T-cell therapy targets nonviral tumor antigens in patients with HPV(+) cervical cancer.
April 21, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28429069/mupexi-prediction-of-neo-epitopes-from-tumor-sequencing-data
#8
Anne-Mette Bjerregaard, Morten Nielsen, Sine Reker Hadrup, Zoltan Szallasi, Aron Charles Eklund
Personalization of immunotherapies such as cancer vaccines and adoptive T cell therapy depends on identification of patient-specific neo-epitopes that can be specifically targeted. MuPeXI, the mutant peptide extractor and informer, is a program to identify tumor-specific peptides and assess their potential to be neo-epitopes. The program input is a file with somatic mutation calls, a list of HLA types, and optionally a gene expression profile. The output is a table with all tumor-specific peptides derived from nucleotide substitutions, insertions, and deletions, along with comprehensive annotation, including HLA binding and similarity to normal peptides...
April 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28428503/-cancer-immunotherapy-utilizing-t-cell-receptor-gene-engineering
#9
Hiroaki Ikeda
Immune-checkpoint inhibitors have shown their efficacy in the treatment of patients with many kinds of progressive/relapsed cancers. However, the efficacy remains as 10-40%of the patients in most type of cancers, suggesting that the development of new therapy for patients resistant to the therapy is an urgent unmet need. Adoptive therapy with tumor-specific T cells is a promising therapy that can be effective in patients who are not benefited from the immune-checkpoint inhibitors. The T cell therapy with genetic engineering in T cell receptor(TCR)is expected to be a universal therapy because this therapy can be applicable for patients with many kinds of cancers...
April 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28426455/digoxin-attenuates-murine-experimental-colitis-by-downregulating-th17-related-cytokines
#10
Shinya Tani, Ryosuke Takano, Satoshi Tamura, Shinji Oishi, Moriya Iwaizumi, Yasushi Hamaya, Kosuke Takagaki, Toshi Nagata, Shintaro Seto, Toshinobu Horii, Isao Kosugi, Toshihide Iwashita, Satoshi Osawa, Takahisa Furuta, Hiroaki Miyajima, Ken Sugimoto
BACKGROUND: Digoxin, a cardiac glycoside used for the treatment of heart failure, was reported to inhibit the retinoid-related orphan receptor gamma t (RORγt) and attenuate the severity of experimental autoimmune encephalomyelitis and arthritis in mice. However, the effects of digoxin in a mice model of inflammatory bowel disease have not been elucidated. METHODS: Colitis was induced in severe combined immunodeficiency mice by adoptive transfer of CD45RB CD4 T cells...
May 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28424328/toward-off-the-shelf-adoptive-t-cell-therapies
#11
Kwanghun Chung
Artificial thymic organoids may enable more efficient engineered T cell production for immunotherapy.
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28423678/influence-of-ipilimumab-on-expanded-tumour-derived-t-cells-from-patients-with-metastatic-melanoma
#12
Jon Bjoern, Rikke Lyngaa, Rikke Andersen, Lisbet Hölmich Rosenkrantz, Sine Reker Hadrup, Marco Donia, Inge Marie Svane
INTRODUCTION: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy (ACT) is a promising treatment for patients with advanced melanoma. Retrospective studies suggested an association between previous treatment with anti-CTLA-4 antibodies and long term survival after subsequent ACT. Thus, we hypothesized that treatment with anti-CTLA-4 antibodies can induce favourable changes to be detected in TILs. RESULTS: Expanded T cells from Ipilimumab treated patients had a higher proportion of cells expressing CD27, intracellular CTLA-4, TIM-3 and LAG-3...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422742/multi-omics-study-revealing-the-complexity-and-spatial-heterogeneity-of-tumor-infiltrating-lymphocytes-in-primary-liver-carcinoma
#13
Lijun Shi, Yang Zhang, Lin Feng, Liming Wang, Weiqi Rong, Fan Wu, Jianxiong Wu, Kaitai Zhang, Shujun Cheng
Intratumoral heterogeneity has been revealed in primary liver carcinoma (PLC). However, spatial heterogeneity of tumor-infiltrating lymphocytes (TILs), which reflects one dimension of a tumor's spatial heterogeneity, and the relationship between TIL diversity, local immune response and mutation burden remain unexplored in PLC. Therefore, we performed immune repertoire sequencing, gene expression profiling analysis and whole-exome sequencing in parallel on five regions of each tumor and on matched adjacent normal tissues and peripheral blood from five PLC patients...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411126/low-interleukin-2-concentration-favors-generation-of-early-memory-t-cells-over-effector-phenotypes-during-chimeric-antigen-receptor-t-cell-expansion
#14
Tanja Kaartinen, Annu Luostarinen, Pilvi Maliniemi, Joni Keto, Mikko Arvas, Heini Belt, Jonna Koponen, Angelica Loskog, Satu Mustjoki, Kimmo Porkka, Seppo Ylä-Herttuala, Matti Korhonen
BACKGROUND: Adoptive T-cell therapy offers new options for cancer treatment. Clinical results suggest that T-cell persistence, depending on T-cell memory, improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is not straightforward because it drives effector T-cell differentiation but does not promote the formation of T-cell memory. We have developed a cost-effective expansion protocol for chimeric antigen receptor (CAR) T cells with an early memory phenotype...
April 11, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28410303/personalized-therapy-tumor-antigen-discovery-for-adoptive-cellular-therapy
#15
Cassian Yee, Gregory A Lizee
Adoptive cell therapy using endogenous T cells involves the ex vivo isolation and expansion of antigen-specific T cells from the peripheral blood and is uniquely suited for validating and translating antigen discovery. Endogenous T-cell therapy does not require accessible tumor as a source of infiltrating T cells and is free of regulatory and logistical constraints associated with engineering T cells. Candidate epitope peptides identified through antigen discovery may be rapidly implemented as targets in clinical trials of endogenous T-cell therapy and even incorporated as an "ad hoc" approach to personalized treatment when autologous tumor is available...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28410302/tumor-infiltrating-lymphocyte-therapy-and-neoantigens
#16
Paul F Robbins
The adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes has been shown to be effective at mediating tumor regression in more than half of patients with metastatic melanoma and in mediating long-term complete regression in approximately one fourth of all patients with this cancer. The success of this approach in patients with cholangiocarcinoma and colon cancer supports efforts to expand ACT therapies to treatment of patients bearing a wide array of cancer types. Recent improvements in deep sequencing of the patient cancers, combined with extensive immunological testing of autologous tumor-infiltrating lymphocytes, indicate that T cells targeting epitopes arising from nonsynonymous somatic mutations, termed neoantigens, play important roles in mediating many of the effective cancer immunotherapies seen in response to ACT...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28408606/landscape-of-immunogenic-tumor-antigens-in-successful-immunotherapy-of-virally-induced-epithelial-cancer
#17
Sanja Stevanović, Anna Pasetto, Sarah R Helman, Jared J Gartner, Todd D Prickett, Bryan Howie, Harlan S Robins, Paul F Robbins, Christopher A Klebanoff, Steven A Rosenberg, Christian S Hinrichs
Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus-associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens...
April 14, 2017: Science
https://www.readbyqxmd.com/read/28405508/antigen-receptor-redirected-t-cells-derived-from-hematopoietic-precursor-cells-lack-expression-of-the-endogenous-tcr-cd3-receptor-and-exhibit-specific-antitumor-capacities
#18
Yasmine Van Caeneghem, Stijn De Munter, Paola Tieppo, Glenn Goetgeluk, Karin Weening, Greet Verstichel, Sarah Bonte, Tom Taghon, Georges Leclercq, Tessa Kerre, Reno Debets, David Vermijlen, Hinrich Abken, Bart Vandekerckhove
Recent clinical studies indicate that adoptive T-cell therapy and especially chimeric antigen receptor (CAR) T-cell therapy is a very potent and potentially curative treatment for B-lineage hematologic malignancies. Currently, autologous peripheral blood T cells are used for adoptive T-cell therapy. Adoptive T cells derived from healthy allogeneic donors may have several advantages; however, the expected occurrence of graft versus host disease (GvHD) as a consequence of the diverse allogeneic T-cell receptor (TCR) repertoire expressed by these cells compromises this approach...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405496/il-12-il-15-and-il-18-pre-activated-nk-cells-target-resistant-t-cell-acute-lymphoblastic-leukemia-and-delay-leukemia-development-in-vivo
#19
Margherita Boieri, Aina Ulvmoen, Amanda Sudworth, Clare Lendrem, Matthew Collin, Anne M Dickinson, Lise Kveberg, Marit Inngjerdingen
NK cells have shown promise in therapy of hematological cancers, in particular against acute myeloid leukemia. In contrast, the more NK cell-resistant acute lymphoblastic leukemia (ALL) is difficult to treat with NK-cell-based therapies, and we hypothesized that pre-activation of NK cells could overcome this resistance. We show in pediatric and adult patients with T-cell ALL (T-ALL) perturbed NK cell effector functions at diagnosis. Using an in vivo rat model for T-ALL, Roser leukemia (RL), suppressed NK cell effector functions were observed...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28401257/ido-and-galectin-3-hamper-the-ex-vivo-generation-of-clinical-grade-tumor-specific-t-cells-for-adoptive-cell-therapy-in-metastatic-melanoma
#20
Sara M Melief, Marten Visser, Sjoerd H van der Burg, Els M E Verdegaal
Adoptive T cell transfer (ACT) with ex vivo-expanded tumor-reactive T cells proved to be successful for the treatment of metastatic melanoma patients. Mixed lymphocyte tumor cell cultures (MLTC) can be used to generate tumor-specific T cells for ACT; however, in a number of cases tumor-reactive T cell, expansion is far from optimal. We hypothesized that this is due to tumor intrinsic and extrinsic factors and aimed to identify and manipulate these factors so to optimize our clinical, GMP-compliant MLTC protocol...
April 11, 2017: Cancer Immunology, Immunotherapy: CII
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