Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia.

Abstract:

:The engineering of T lymphocytes to express chimeric antigen receptors (CARs) aims to establish T cell-mediated tumor immunity rapidly. In this study, we conducted a pilot clinical trial of autologous or donor- derived T cells genetically modified to express a CAR targeting the B-cell antigen CD19 harboring 4-1BB and the CD3ζ moiety. All enrolled patients had relapsed or chemotherapy-refractory B-cell lineage acute lymphocytic leukemia (B-ALL). Of the nine patients, six had definite extramedullary involvement, and the rate of overall survival at 18 weeks was 56%. One of the two patients who received conditioning chemotherapy achieved a three-month durable complete response with partial regression of extramedullary lesions. Four of seven patients who did not receive conditioning chemotherapy achieved dramatic regression or a mixed response in the haematopoietic system and extramedullary tissues for two to nine months. Grade 2-3 graft-versus-host disease (GVHD) was observed in two patients who received substantial donor-derived anti-CD19 CART (chimeric antigen receptor-modified T) cells 3-4 weeks after cell infusions. These results show for the first time that donor-derived anti-CD19 CART cells can cause GVHD and regression of extramedullary B-ALL. This study is registered at www.clinicaltrials.gov as NCT01864889.

journal_name

Oncoimmunology

journal_title

Oncoimmunology

authors

Dai H,Zhang W,Li X,Han Q,Guo Y,Zhang Y,Wang Y,Wang C,Shi F,Zhang Y,Chen M,Feng K,Wang Q,Zhu H,Fu X,Li S,Han W

doi

10.1080/2162402X.2015.1027469

subject

Has Abstract

pub_date

2015-05-26 00:00:00

pages

e1027469

issue

11

eissn

2162-4011

issn

2162-402X

pii

1027469

journal_volume

4

pub_type

杂志文章
  • Bone marrow provides an environment that prevents suppression of therapeutic graft-vs.-tumor immunity by regulatory T cells.

    abstract::Regulatory T cells (Tregs) can prevent graft-vs.-host disease as induced by the infusion of donor lymphocytes to cancer patients, but often they also suppress therapeutic antitumor immunity. We discuss an exception to this phenomenon, exemplifying how the milieu provided by the bone marrow may neutralize Tregs to allo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.24659

    authors: Guichelaar T,Mutis T

    更新日期:2013-07-01 00:00:00

  • CAR-T cells are serial killers.

    abstract::Chimeric antigen receptor (CAR) T cells have enjoyed unprecedented clinical success against haematological malignancies in recent years. However, several aspects of CAR T cell biology remain unknown. We recently compared CAR and T cell receptor (TCR)-based killing in the same effector cell and showed that CAR T cells ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1053684

    authors: Davenport AJ,Jenkins MR,Ritchie DS,Prince HM,Trapani JA,Kershaw MH,Darcy PK,Neeson PJ

    更新日期:2015-06-01 00:00:00

  • A single centre phase II trial to assess the immunological activity of TroVax® plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma - the SKOPOS trial.

    abstract::Vaccines in combination with chemotherapy have been shown to be safe in different tumor types. We investigated the immunological activity of the TroVax® vaccine in combination with pemetrexed-cisplatin chemotherapy in malignant pleural mesothelioma (MPM). In this first line, open-label, single-arm, phase 2 study, pati...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1457597

    authors: Lester JF,Casbard AC,Al-Taei S,Harrop R,Katona L,Attanoos RL,Tabi Z,Griffiths GO

    更新日期:2018-09-07 00:00:00

  • Ipilimumab administered to metastatic melanoma patients who progressed after dendritic cell vaccination.

    abstract:BACKGROUND:Ipilimumab has proven to be effective in metastatic melanoma patients. The purpose of this study was to determine the efficacy of ipilimumab in advanced melanoma patients who showed progressive disease upon experimental dendritic cell (DC) vaccination. METHODS:Retrospective analysis of 48 stage IV melanoma ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1201625

    authors: Boudewijns S,Koornstra RH,Westdorp H,Schreibelt G,van den Eertwegh AJ,Geukes Foppen MH,Haanen JB,de Vries IJ,Figdor CG,Bol KF,Gerritsen WR

    更新日期:2016-06-17 00:00:00

  • Bioreactors get personal.

    abstract::Adoptive cell transfer immunotherapy against melanoma is highly effective. However, this therapy has seen limited dissemination, mainly due to the complexity and costs of cell expansion protocols. Two bioreactors have recently been described that simplify and streamline the production of individualized cell therapies....

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21206

    authors: Somerville RP,Dudley ME

    更新日期:2012-11-01 00:00:00

  • PD-L1 expression in metastatic neuroblastoma as an additional mechanism for limiting immune surveillance.

    abstract::The prognosis of high-risk neuroblastoma (NB) remains poor, although immunotherapies with anti-GD2 antibodies have been reported to provide some benefit. Immunotherapies can be associated with an IFNγ storm that induces in tumor cells the "adaptive immune resistance" characterized by the de-novo expression of Programm...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1064578

    authors: Dondero A,Pastorino F,Della Chiesa M,Corrias MV,Morandi F,Pistoia V,Olive D,Bellora F,Locatelli F,Castellano A,Moretta L,Moretta A,Bottino C,Castriconi R

    更新日期:2015-07-15 00:00:00

  • The STING agonist DMXAA triggers a cooperation between T lymphocytes and myeloid cells that leads to tumor regression.

    abstract::Regressing tumors are usually associated with a large immune infiltrate, but the molecular and cellular interactions that govern a successful anti-tumor immunity remain elusive. Here, we have triggered type I Interferon (IFN) signaling in a breast tumor model (MMTV-PyMT) using 5,6-dimethylxanthenone-4-acetic acid (DMX...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1346765

    authors: Weiss JM,Guérin MV,Regnier F,Renault G,Galy-Fauroux I,Vimeux L,Feuillet V,Peranzoni E,Thoreau M,Trautmann A,Bercovici N

    更新日期:2017-07-07 00:00:00

  • New role of Interleukin-10 in enhancing the antitumor efficacy of oncolytic vaccinia virus for treatment of pancreatic cancer.

    abstract::Although the profile of safety of tumor-targeted oncolytic virus (TOV) is encouraging, the antitumor efficacy of TOV alone is disappointing. Interleukin-10 (IL-10) plays an important role in carcinogenesis and anti-virus immunity. Here we report that tumor-targeted oncolytic vaccinia virus (VV) armed with IL10 shows p...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1038689

    authors: Chard LS,Lemoine NR,Wang Y

    更新日期:2015-07-20 00:00:00

  • eIF2α phosphorylation: A hallmark of immunogenic cell death.

    abstract::Immunogenic cell death (ICD) induced by anticancer chemotherapeutics is usually preceded by premortem stress affecting the endoplasmic reticulum (ER). This ER stress does not reflect a canonical unfolded protein response (UPR) but rather manifests solely at the level of the phosphorylation of eIF2α. eIF2α phosphorylat...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1431089

    authors: Bezu L,Sauvat A,Humeau J,Leduc M,Kepp O,Kroemer G

    更新日期:2018-02-14 00:00:00

  • Acute myeloid leukemia and NK cells: two warriors confront each other.

    abstract::Acute myeloid leukemia (AML) is a heterogeneous disease whose therapies currently show elevated toxicity and a high rate of relapse. Recently, the burgeoning of new anti-tumor therapeutic strategies aimed at enhancing the immune response has pushed natural killer cells (NKs) into the spotlight. These cells are powerfu...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2018.1539617

    authors: Baragaño Raneros A,López-Larrea C,Suárez-Álvarez B

    更新日期:2018-10-31 00:00:00

  • Invariant NKT cells: Killers and conspirators against cancer.

    abstract::Although invariant natural killer T (iNKT) cells influence antitumor responses indirectly by secreting cytokines and promoting the cytolytic functions of T and NK cells, we find that iNKT cells mediate direct tumoricidal activity in vitro and significantly inhibit tumor growth in vivo, even in the absence of other cyt...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.27440

    authors: Bassiri H,Das R,Nichols KE

    更新日期:2013-12-01 00:00:00

  • Targeting the C-terminus of galectin-9 induces mesothelioma apoptosis and M2 macrophage depletion.

    abstract::Galectin-9 has emerged as a promising biological target for cancer immunotherapy due to its role as a regulator of macrophage and T-cell differentiation. In addition, its expression in tumor cells modulates tumor cell adhesion, metastasis, and apoptosis. Malignant mesothelioma (MM) is an aggressive neoplasm of the mes...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1601482

    authors: Bertino P,Premeaux TA,Fujita T,Haun BK,Marciel MP,Hoffmann FW,Garcia A,Yiang H,Pastorino S,Carbone M,Niki T,Berestecky J,Hoffmann PR,Ndhlovu LC

    更新日期:2019-04-17 00:00:00

  • Blockade of Tumor-Expressed PD-1 promotes lung cancer growth.

    abstract::Anti-PD-1 immunotherapy is the standard of care for treating many patients with non-small cell lung cancer (NSCLC), yet mechanisms of treatment failure are emerging. We present a case of NSCLC, who rapidly progressed during a trial (NCT02318771) combining palliative radiotherapy and pembrolizumab. Planned tumor biopsy...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1408747

    authors: Du S,McCall N,Park K,Guan Q,Fontina P,Ertel A,Zhan T,Dicker AP,Lu B

    更新日期:2018-01-29 00:00:00

  • The pancreatic cancer microenvironment: an immunologic battleground.

    abstract::Recent studies of human pancreatic cancer challenge the mouse model-derived notion that the pancreas is a site of immune privilege. A heavy infiltration of CD8+ T cells expressing programmed cell death 1 (PD-1) and smaller numbers of myeloid cells and regulatory T cells provides rationale for the clinical evaluation o...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.950171

    authors: Pillarisetty VG

    更新日期:2014-08-03 00:00:00

  • Hypoxia-inducible factor 1: A link between metabolism and T cell differentiation and a potential therapeutic target.

    abstract::Naïve T cells activated by antigen-presenting cells (APC) can be differentiated into at least four major types of T-helper (T(H)) cells: T(H)1, T(H)2, T(H)17 and inducible regulatory T cells (iTreg) based on their unique cytokine production profiles and characteristic functions.(1) T(H)1 produce interferon-γ (IFNγ) an...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.19457

    authors: Pan F,Barbi J,Pardoll DM

    更新日期:2012-07-01 00:00:00

  • Trial Watch: Toll-like receptor agonists for cancer therapy.

    abstract::Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitat...

    journal_title:Oncoimmunology

    pub_type: 评审

    doi:10.4161/onci.25238

    authors: Vacchelli E,Eggermont A,Sautès-Fridman C,Galon J,Zitvogel L,Kroemer G,Galluzzi L

    更新日期:2013-08-01 00:00:00

  • Maytansine-bearing antibody-drug conjugates induce in vitro hallmarks of immunogenic cell death selectively in antigen-positive target cells.

    abstract::Oncology treatment has been revolutionized by the introduction of immune checkpoint inhibitor drugs, which enable 20-40% of patients to generate anti-tumor immune responses. Combination treatment approaches with chemotherapeutic drugs may enable responses in the remaining patient cohorts. In this regard, a handful of ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1565859

    authors: Bauzon M,Drake PM,Barfield RM,Cornali BM,Rupniewski I,Rabuka D

    更新日期:2019-01-22 00:00:00

  • Instruction of myeloid cells by the tumor microenvironment: Open questions on the dynamics and plasticity of different tumor-associated myeloid cell populations.

    abstract::The versatility and plasticity of myeloid cell polarization/differentiation has turned out to be crucial in health and disease, and has become the subject of intense investigation during the last years. On one hand, myeloid cells provide a critical contribution to tissue homeostasis and repair. On the other hand, myel...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21566

    authors: Schouppe E,De Baetselier P,Van Ginderachter JA,Sarukhan A

    更新日期:2012-10-01 00:00:00

  • IL-33 increases ST2+ Tregs and promotes metastatic tumour growth in the lungs in an amphiregulin-dependent manner.

    abstract::Regulatory T cells (Tregs) facilitate primary and metastatic tumour growth through the suppression of anti-tumour immunity. Emerging evidence suggests a distinct role for Tregs in mediating tissue repair and barrier integrity in the lungs by IL-33 mediated production of the growth factor amphiregulin (AREG). Dependent...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1527497

    authors: Halvorsen EC,Franks SE,Wadsworth BJ,Harbourne BT,Cederberg RA,Steer CA,Martinez-Gonzalez I,Calder J,Lockwood WW,Bennewith KL

    更新日期:2018-10-16 00:00:00

  • Differential potency of regulatory T cell-mediated immunosuppression in kidney tumors compared to subcutaneous tumors.

    abstract::In many cancers, regulatory T cells (Treg) play a crucial role in suppressing the effector immune response thereby permitting tumor development. Indeed, in mouse models, their depletion can promote the regression of tumors of various origins, including renal cell carcinoma when located subcutaneous (SC). In the presen...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.963395

    authors: Devaud C,Westwood JA,Teng MW,John LB,Yong CS,Duong CP,Smyth MJ,Darcy PK,Kershaw MH

    更新日期:2014-12-21 00:00:00

  • Tbet and IL-36γ cooperate in therapeutic DC-mediated promotion of ectopic lymphoid organogenesis in the tumor microenvironment.

    abstract::We have previously reported that direct injection of dendritic cells (DC) engineered to express the Type-1 transactivator Tbet (i.e., DC.Tbet) into murine tumors results in antitumor efficacy in association with the development of structures resembling tertiary lymphoid organs (TLO) in the tumor microenvironment (TME)...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1322238

    authors: Weinstein AM,Chen L,Brzana EA,Patil PR,Taylor JL,Fabian KL,Wallace CT,Jones SD,Watkins SC,Lu B,Stroncek DF,Denning TL,Fu YX,Cohen PA,Storkus WJ

    更新日期:2017-04-28 00:00:00

  • Resistance of cyclooxygenase-2 expressing pancreatic ductal adenocarcinoma cells against γδ T cell cytotoxicity.

    abstract::The prostaglandin (PG) synthetase cyclooxygenase 2 (Cox-2) promotes tumorigenesis, tumor progression, and metastasis in a variety of human cancer entities including pancreatic ductal adenocarcinoma (PDAC). In this study, we demonstrate that in PDAC cells such as Colo357 cells, enhanced Cox-2 expression and increased r...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/2162402X.2014.988460

    authors: Gonnermann D,Oberg HH,Kellner C,Peipp M,Sebens S,Kabelitz D,Wesch D

    更新日期:2015-01-07 00:00:00

  • The role of NF-kB in modulating antitumor immunity.

    abstract::Recent breakthroughs in therapeutic modulation of immune cells have led to novel exciting treatments for cancers. Moreover, the cytokine milieu in the tumor microenvironment is important for appropriate immune surveillance. Here, we demonstrate that NF-κB activity in myeloid cells is essential for cytokine-mediated an...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1005522

    authors: Richmond A,Yang J

    更新日期:2015-10-20 00:00:00

  • Depletion of B220+NK1.1+ cells enhances the rejection of established melanoma by tumor-specific CD4+ T cells.

    abstract::Five-year survival rates for patients diagnosed with metastatic melanoma are less than 5%. Adoptive cell transfer (ACT) has achieved an objective response of 50% by Response Evaluation Criteria in Solid Tumors (RECIST) in this patient population. For ACT to be maximally effective, the host must first be lymphodepleted...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1019196

    authors: Wilson KA,Goding SR,Neely HR,Harris KM,Antony PA

    更新日期:2015-04-01 00:00:00

  • The immune molecular landscape of the B7 and TNFR immunoregulatory ligand-receptor families in head and neck cancer: A comprehensive overview and the immunotherapeutic implications.

    abstract::The B7 family and tumor necrosis factor receptor (TNFR) superfamily play a vital role in the T-cell co-stimulatory and co-inhibitory pathways, regulating T-cell activation, tolerance, and exhaustion; therapeutic modulation of these pathways is translated into effective new cancer treatments. Better understanding of th...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1288329

    authors: Chen YP,Zhang J,Wang YQ,Liu N,He QM,Yang XJ,Sun Y,Ma J

    更新日期:2017-02-16 00:00:00

  • Cell-type specific MyD88 signaling is required for intestinal tumor initiation and progression to malignancy.

    abstract::The signal adapter MyD88, an essential component of Toll-like receptor (TLR) signaling, is important for gut-microbiome interactions. However, its contribution to cancer and its cell-type specific functions are controversially discussed. Therefore, we generated new tissue-specific mouse models and analyzed the clinica...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1466770

    authors: Holtorf A,Conrad A,Holzmann B,Janssen KP

    更新日期:2018-06-11 00:00:00

  • Tumor infiltrating CD8+ T lymphocyte count is independent of tumor TLR9 status in treatment naïve triple negative breast cancer and renal cell carcinoma.

    abstract::Toll-like receptor 9 (TLR9) is a cellular DNA-receptor of the innate immune system that is widely expressed in cancers. We demonstrated that low tumor TLR9 expression predicts poor disease-specific survival in triple negative breast cancer (TNBC) and renal cell carcinoma (RCC). We hypothesized that this is because TLR...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2014.1002726

    authors: Mella M,Kauppila JH,Karihtala P,Lehenkari P,Jukkola-Vuorinen A,Soini Y,Auvinen P,Vaarala MH,Ronkainen H,Kauppila S,Haapasaari KM,Vuopala KS,Selander KS

    更新日期:2015-05-22 00:00:00

  • Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxin.

    abstract::Granulysin is a protein present in the granules of human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, with cytolytic activity against microbes and tumors. Previous work demonstrated the therapeutic effect of intratumoral injection of recombinant granulysin using in vivo models of breast cancer and mult...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1641392

    authors: Ibáñez-Pérez R,Guerrero-Ochoa P,Al-Wasaby S,Navarro R,Tapia-Galisteo A,De Miguel D,Gonzalo O,Conde B,Martínez-Lostao L,Hurtado-Guerrero R,Sanz L,Anel A

    更新日期:2019-07-22 00:00:00

  • Non-V delta 2 gamma delta T lymphocytes as effectors of cancer immunotherapy.

    abstract::Gamma delta T cells (γδT) are potent mediators of antitumor cytotoxicity and have shown promising efficacy in early phase clinical trials. Most is known about the tumoricidal properties of cells bearing the Vδ2 T cell receptor chain, but recent studies have demonstrated that cells with the Vδ1 chain and those with nei...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/2162402X.2014.973808

    authors: Fisher J,Kramer AM,Gustafsson K,Anderson J

    更新日期:2014-12-23 00:00:00

  • The myeloid response to pancreatic carcinogenesis is regulated by the receptor for advanced glycation end-products.

    abstract::We identified a critical role for receptor for advanced glycation end products (RAGE) in the intratumoral accumulation of myeloid-derived suppressor cells (MDSCs) during pancreatic carcinogenesis. The absence of RAGE markedly delayed neoplasia and limited MDSC accumulation in mice expressing an oncogenic variant of Kr...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.24184

    authors: Vernon PJ,Zeh Iii HJ,Lotze MT

    更新日期:2013-05-01 00:00:00