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Adoptive immunotherapy

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https://www.readbyqxmd.com/read/29340102/the-impact-of-antibiotic-usage-on-the-efficacy-of-chemoimmunotherapy-is-contingent-on-the-source-of-tumor-reactive-t-cells
#1
Michal P Kuczma, Zhi-Chun Ding, Tao Li, Tsadik Habtetsion, Tingting Chen, Zhonglin Hao, Locke Bryan, Nagendra Singh, James N Kochenderfer, Gang Zhou
In recent years the combined use of chemotherapy and immunotherapy, collectively termed chemoimmunotherapy, has emerged as a promising treatment option for patients with cancer. Antibiotics are commonly used to reduce infection-related complications in patients undergoing chemotherapy. Intriguingly, accumulating evidence has implicated gut microbiota as a critical determinant of host antitumor immune responses, raising the question as to whether the use of broad-spectrum antibiotics would invariably diminish tumor response to chemoimmunotherapies...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339767/regulatory-t-cells-trigger-effector-t-cell-dna-damage-and-senescence-caused-by-metabolic-competition
#2
Xia Liu, Wei Mo, Jian Ye, Lingyun Li, Yanping Zhang, Eddy C Hsueh, Daniel F Hoft, Guangyong Peng
Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical for the development of effective strategies for treating tumors and chronic infections. The molecular processes that occur in responder T cells that are suppressed by Treg cells are unclear. Here we show that human Treg cells initiate DNA damage in effector T cells caused by metabolic competition during cross-talk, resulting in senescence and functional changes that are molecularly distinct from anergy and exhaustion. ERK1/2 and p38 signaling cooperate with STAT1 and STAT3 to control Treg-induced effector T-cell senescence...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29331106/kbtbd2-inhibits-the-cytotoxic-activity-of-immortalized-nk-cells-through-down-regulating-mtor-signaling-in-a-mouse-hepatocellular-carcinoma-model
#3
Kai Dai, Yabing Huang, Zubing Chen, Xiaomei Sun, Lihua Yang, Yingan Jiang
Natural killer cell (NK cell)-based immunotherapy is a promising therapeutic strategy for hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the regulation of NK cell function in the tumor sites are not completely elucidated. In this study, we identified the enhanced expression of kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) in intratumoral NK cells in a mouse HCC implantation model as a negative regulator of NK cells. To investigate this interaction,, we used a Tet-on inducible expression system to control Kbtbd2 expression in an immortalized mouse NK cell line KIL C...
January 13, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29329591/prospects-for-chimeric-antigen-receptor-modified-t-cell-therapy-for-solid-tumors
#4
REVIEW
Erhao Zhang, Jieyi Gu, Hanmei Xu
The potential for adoptive cell immunotherapy as a treatment against cancers has been demonstrated by the remarkable response in some patients with hematological malignancies using autologous T cells endowed with chimeric antigen receptors (CARs) specific for CD19. Clinical efficacy of CAR-T cell therapy for the treatment of solid tumors, however, is rare due to physical and biochemical factors. This review focuses on different aspects of multiple mechanisms of immunosuppression in solid tumors. We characterize the current state of CAR-modified T cell therapy and summarize the various strategies to combat the immunosuppressive microenvironment of solid tumors, with the aim of promoting T cell cytotoxicity and enhancing tumor cell eradication...
January 12, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29329051/non-genetic-engineering-of-cytotoxic-t-cells-to-target-il-4-receptor-enhances-tumor-homing-and-therapeutic-efficacy-against-melanoma
#5
Gowri Rangaswamy Gunassekaran, Chae-Moon Hong, Sri Murugan Poongkavithai Vadevoo, Lianhua Chi, Padmanaban Guruprasath, Byung-Cheol Ahn, Ha-Jeong Kim, Tae Heung Kang, Byungheon Lee
Adoptive transfer of cytotoxic T lymphocytes (CTLs) has been used as an immunotherapy in melanoma. However, the tumor homing and therapeutic efficacy of transferred CTLs against melanoma remain unsatisfactory. Interleukin-4 receptor (IL-4R) is commonly up-regulated in tumors including melanoma. Here, we studied whether IL-4R-targeted CTLs exhibit enhanced tumor homing and therapeutic efficacy against melanoma. CTLs isolated from mice bearing melanomas were non-genetically engineered with IL4RPep-1, an IL-4R-binding peptide, using a membrane anchor composed of dioleylphosphatidylethanolamine...
January 8, 2018: Biomaterials
https://www.readbyqxmd.com/read/29327110/the-role-of-interleukin-2-all-trans-retinoic-acid-and-natural-killer-cells-surveillance-mechanisms-in-anti-gd2-antibody-therapy-in-neuroblastoma
#6
Rosa Nguyen, Jim Houston, Wing K Chan, David Finkelstein, Michael A Dyer
Although anti-disialoganglioside (GD2) antibodies are successfully used for neuroblastoma therapy, a third of patients with neuroblastoma experience treatment failure or serious toxicity. Various strategies have been employed in the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell function, adoptive transfer of allogeneic NK cells to exploit immune surveillance, and retinoid-induced differentiation therapy...
January 11, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29321210/the-immune-checkpoint-modulator-ox40-and-its-ligand-ox40l-in-nk-cell-immunosurveillance-and-acute-myeloid-leukemia
#7
Tina Nuebling, Carla Emilia Schumacher, Martin Hofmann, Ilona Hagelstein, Benjamin Joachim Schmiedel, Stefanie Maurer, Birgit Federmann, Kathrin Rothfelder, Malte Roerden, Daniela Dorfel, Pascal Schneider, Gundram Jung, Helmut Rainer Salih
The TNF receptor family member OX40 promotes activation and proliferation of T cells, which fuels efforts to modulate this immune checkpoint to reinforce antitumor immunity. Besides T cells, NK cells are a second cytotoxic lymphocyte subset that contributes to antitumor immunity, particularly in leukemia. Accordingly, these cells are being clinically evaluated for cancer treatment through multiple approaches, such as adoptive transfer of ex vivo expanded polyclonal NK cells (pNKC). Here we analyzed whether and how OX40 and its ligand (OX40L) influence NK-cell function and anti-leukemia reactivity...
January 10, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29319881/systemic-il-2-anti-il-2ab-complex-combined-with-sublingual-immunotherapy-suppresses-experimental-food-allergy-in-mice-through-induction-of-mucosal-regulatory-t-cells
#8
Paola L Smaldini, Fernando Trejo, José L Cohen, Eliane Piaggio, Guillermo H Docena
Therapeutic tolerance restoration has been proven to modify food allergy in patients and animal models and although sublingual immunotherapy (SLIT) has showed promise, combined therapy may be necessary to achieve a strong and long-term tolerance. In this work, we combined SLIT with systemic administration of IL-2 associated with an anti-IL-2 monoclonal antibody (IL-2/anti-IL-2Ab complex or IL-2C) to reverse the IgE-mediated experimental allergy. Balb/c mice were sensitized with cholera toxin and milk proteins and orally challenged with allergen to elicit hypersensitivity reactions...
January 10, 2018: Allergy
https://www.readbyqxmd.com/read/29316940/gamma-delta-%C3%AE-%C3%AE-t-cells-friend-or-foe-in-cancer-development
#9
REVIEW
Yijing Zhao, Chao Niu, Jiuwei Cui
BACKGROUND: γδ T cells are a distinct subgroup of T cells containing T cell receptors (TCRs) γ and TCR δ chains with diverse structural and functional heterogeneity. As a bridge between the innate and adaptive immune systems, γδ T cells participate in various immune responses during cancer progression. Because of their direct/indirect antitumor cytotoxicity and strong cytokine production ability, the use of γδ T cells in cancer immunotherapy has received a lot of attention over the past decade...
January 10, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29313971/in-vivo-antitumor-function-of-tumor-antigen-specific-ctls-generated-in-the-presence-of-ox40-co-stimulation-in-vitro
#10
Ngoc Pham Minh, Satoshi Murata, Naomi Kitamura, Tomoyuki Ueki, Masatsugu Kojima, Toru Miyake, Katsushi Takebayashi, Hirokazu Kodama, Eiji Mekata, Masaji Tani
Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8+ T-cells, co-cultured with a tumor specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine...
January 4, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29311309/signaling-by-the-epstein-barr-virus-lmp1-protein-induces-potent-cytotoxic-cd4-and-cd8-t-cell-responses
#11
Il-Kyu Choi, Zhe Wang, Qiang Ke, Min Hong, Yu Qian, Xiujuan Zhao, Yuting Liu, Hye-Jung Kim, Jerome Ritz, Harvey Cantor, Klaus Rajewsky, Kai W Wucherpfennig, Baochun Zhang
The B-lymphotropic Epstein-Barr virus (EBV), pandemic in humans, is rapidly controlled on initial infection by T cell surveillance; thereafter, the virus establishes a lifelong latent infection in the host. If surveillance fails, fatal lymphoproliferation and lymphomagenesis ensue. The initial T cell response consists of predominantly CD8+ cytotoxic T cells and a smaller expansion of CD4+ cells. A major approach to treating EBV-associated lymphomas is adoptive transfer of autologous or allogeneic T cells that are stimulated/expanded on EBV-transformed B cells...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29308300/co-stimulatory-signaling-determines-tumor-antigen-sensitivity-and-persistence-of-car-t-cells-targeting-psca-metastatic-prostate-cancer
#12
Saul J Priceman, Ethan A Gerdts, Dileshni Tilakawardane, Kelly T Kennewick, John P Murad, Anthony K Park, Brook Jeang, Yukiko Yamaguchi, Xin Yang, Ryan Urak, Lihong Weng, Wen-Chung Chang, Sarah Wright, Sumanta Pal, Robert E Reiter, Anna M Wu, Christine E Brown, Stephen J Forman
Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with "on-target off-tumor" activity...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29307234/reprogramming-t-cells-for-adoptive-immunotherapy-of-ovarian-cancer
#13
Sofia Genta, Eleonora Ghisoni, Gaia Giannone, Gloria Mittica, Giorgio Valabrega
Epithelial ovarian cancer (EOC) is the most common cause of death among gynecological malignancies. Despite surgical and pharmacological efforts to improve patients' outcome, persistent and recurrent EOC remains an un-eradicable disease. Chimeric associated antigens (CAR) T cells are T lymphocytes expressing an engineered T cell receptor that activate the immune response after an MHC unrestricted recognition of specific antigens, including tumor associated antigens (TAAs). CART cells have been shown to be effective in the treatment of hematologic tumors even if frequently associated with potentially severe toxicity and high production costs...
January 10, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29305520/soluble-slamf6-receptor-induces-strong-cd8-t-cell-effector-function-and-improves-anti-melanoma-activity-in-vivo
#14
Galit Eisenberg, Roni Engelstein, Anat Geiger, Emma Hajaj, Sharon Merims, Shoshana Frankenburg, Ronny Uzana, Abraham Rutenberg, Arthur Machlenkin, Gabi Frei, Tamar Peretz, Michal Lotem
SLAMF6, a member of the SLAM (signaling lymphocyte activation molecules) family, is a homotypic-binding immune receptor expressed on NK, T, and B lymphocytes. Phosphorylation variance between T-cell subclones prompted us to explore its role in anti-melanoma immunity. Using a 203-amino acid sequence of the human SLAMF6 (seSLAMF6) ectodomain, we found that seSLAMF6 reduced activation-induced cell death and had an anti-apoptotic effect on tumor infiltrating lymphocytes. CD8+ T cells costimulated with seSLAMF6 secreted more interferon gamma and displayed augmented cytolytic activity...
January 5, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29301752/t-cell-responses-in-the-microenvironment-of-primary-renal-cell-carcinoma-implications-for-adoptive-cell-therapy
#15
Rikke Andersen, Marie Christine Wulff Westergaard, Julie Westerlin Kjeldsen, Anja Mueller, Natasja Wulff Pedersen, Sine Reker Hadrup, Ozcan Met, Barbara Seliger, Bjarne Kromann-Andersen, Thomas Hasselager, Marco Donia, Inge Marie Svane
In vitro expansion of large numbers of highly potent tumor-reactive T cells appears a prerequisite for effective adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) as shown in metastatic melanoma (MM). We therefore sought to determine whether renal cell carcinomas (RCC) are infiltrated with tumor-reactive T cells that could be efficiently employed for adoptive transfer immunotherapy. TILs and autologous tumor cell lines (TCLs) were successfully generated from 22 (92%) and 17 (77%) of 24 consecutive primary RCC specimens and compared to those generated from MM...
January 4, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29299660/reduction-of-myeloid-derived-suppressor-cells-reinforces-the-anti-solid-tumor-effect-of-recipient-leukocyte-infusion-in-murine-neuroblastoma-bearing-allogeneic-bone-marrow-chimeras
#16
Isabelle Dierckx de Casterlé, Sabine Fevery, Omer Rutgeerts, Fariba Poosti, Sofie Struyf, Caroline Lenaerts, Mark Waer, An D Billiau, Ben Sprangers
Allogeneic hematopoietic stem cell transplantation is an emerging treatment option for solid tumors because of its capacity to elicit immune graft-versus-tumor effects. However, these are often limited and associated with GvHD. Adoptive recipient leukocyte infusion (RLI) was shown to enhance anti-tumor responses of allogeneic bone marrow transplantation in murine neuroblastoma (Neuro2A)-bearing chimeras. In contrast to the clinically used donor leukocyte infusion, the RLI anti-tumor effect-elicited by host-versus-graft lymphohematopoietic reactivity-does not cause GvHD; however, the tumor growth-inhibitory effect is incomplete, because overall survival is not prolonged...
January 3, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29295873/potentiating-tissue-resident-type-2-innate-lymphoid-cells-by-il-33-to-prevent-renal-ischemia-reperfusion-injury
#17
Qi Cao, Yiping Wang, Zhiguo Niu, Chengshi Wang, Ruifeng Wang, Zhiqiang Zhang, Titi Chen, Xin Maggie Wang, Qing Li, Vincent W S Lee, Qingsong Huang, Jing Tan, Minghao Guo, Yuan Min Wang, Guoping Zheng, Di Yu, Stephen I Alexander, Hui Wang, David C H Harris
The IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI). Compared with control-treated IRI mice, IL-33-treated IRI mice had increased levels of IL-4 and IL-13 in serum and kidney and more ILC2, regulatory T cells (Tregs), and anti-inflammatory (M2) macrophages...
January 2, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29288540/expansion-of-human-%C3%AE-%C3%AE-t-cells-for-adoptive-immunotherapy-using-a-bisphosphonate-prodrug
#18
Yoshimasa Tanaka, Kaoru Murata-Hirai, Masashi Iwasaki, Kenji Matsumoto, Kosuke Hayashi, Asuka Kumagai, Mohanad H Nada, Hong Wang, Hirohito Kobayashi, Hiroshi Kamitakahara, Haruki Okamura, Tomoharu Sugie, Nagahiro Minato, Masakazu Toi, Craig T Morita
Cancer immunotherapy with human γδ T cells expressing Vγ2Vδ2 T cell receptor (also termed Vγ9Vδ2) has shown promise because of their ability to recognize and kill most types of tumors in an MHC-unrestricted fashion that is independent of the number of tumor mutations. In clinical trials, adoptive transfer of Vγ2Vδ2 T cells has been shown to be safe and does not require preconditioning. In this report, we describe a method for preparing highly enriched human Vγ2Vδ2 T cells using the bisphosphonate prodrug, tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate (PTA)...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29288509/cancer-immunotherapy-a-need-for-peripheral-immunodynamic-monitoring
#19
REVIEW
Wenjun Wang, Xiaojun Xia, Sipei Wu, Minzhang Guo, Puyi Lie, Jianxing He
Immunotherapy has become an important approach for treating different tumours which has shown significant efficacy in numerous clinical trials, especially those using new checkpoint inhibitors and adoptive cell therapy, which have rapidly become widespread after being approved. However, analysis of peripheral immune biomarkers before and after immunotherapy and their relationship to clinical responses and disease prognosis have rarely been performed in clinical trials. In this review, we examine dynamic changes in the immune system before and after therapy by analyzing recent clinical trials of immunotherapy in patients with cancer that focused on checkpoint inhibitors and adoptive cell therapy...
December 30, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29285113/low-dose-irradiation-increases-adoptive-cytotoxic-t-lymphocyte-migration-in-gastric-cancer
#20
Juan Du, Shu Su, Hongyan Li, Jie Shao, Fanyan Meng, Mi Yang, Hanqing Qian, Zhengyun Zou, Xiaoping Qian, Baorui Liu
Adoptive cellular immunotherapy (ACI) has been demonstrated to be a promising cancer therapeutic; however, the inefficient migration of adoptive immune cells to tumors is one of the rate-limiting factors of ACI. The present study investigated whether 2 Gy low dose irradiation (LDI) was able to increase the migration of adoptive lymphocytes to gastric cancer cells. Treatment with 2 Gy LDI resulted in marked chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 production from gastric cancer cell lines. A Transwell chamber migration assay demonstrated enhanced transmigration of cytotoxic T lymphocytes to gastric cancer cells following LDI treatment...
December 2017: Experimental and Therapeutic Medicine
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