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 drugs are promising due to their ability to induce immunogenic cell death in target cells. However, these agents are systemically delivered and indiscriminately cytotoxic to proliferating cells. By contrast, antibody-drug conjugates can selectively deliver a cytotoxic payload to a tumor, sparing most healthy cells. The ability of antibody-drug conjugates to induce immunogenic cell death in target cells has not yet been determined, although preclinical in vivo studies suggest this possibility. Here, we describe for the first time production of the in vitro hallmarks of immunogenic cell death - ecto-calreticulin and secreted ATP and HMGB1 protein - by cells in response to treatment with antibody-drug conjugates bearing a maytansine payload.

journal_name

Oncoimmunology

journal_title

Oncoimmunology

authors

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

doi

10.1080/2162402X.2019.1565859

subject

Has Abstract

pub_date

2019-01-22 00:00:00

pages

e1565859

issue

4

eissn

2162-4011

issn

2162-402X

pii

1565859

journal_volume

8

pub_type

杂志文章
  • Strategies for purging CD96+ stem cells in vitro and in vivo: New avenues for autologous stem cell transplantation in acute myeloid leukemia.

    abstract::The persistence of leukemic stem cells (LSCs) in acute myeloid leukemia (AML) patients receiving chemotherapy may be responsible for the high frequency of relapse. The selective elimination of CD96+ AML-LSCs by means of CD96-specific monoclonal antibodies may be a promising therapeutic approach and revitalize autologo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.24500

    authors: Staudinger M,Humpe A,Gramatzki M

    更新日期:2013-06-01 00:00:00

  • Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma.

    abstract::Cutaneous angiosarcoma (CAS) is a malignant sarcoma with poor prognosis. Programmed cell death-1 (PD-1)/programmed cell death-1 ligand-1 (PD-L1) expression reflects antitumor immunity, and is associated with patient prognosis in various cancers. The purpose of this study is to investigate the relationship between PD-1...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1253657

    authors: Honda Y,Otsuka A,Ono S,Yamamoto Y,Seidel JA,Morita S,Hirata M,Kataoka TR,Takenouchi T,Fujii K,Kanekura T,Okubo Y,Takahashi K,Yanagi T,Hoshina D,Hata H,Abe R,Fujimura T,Funakoshi T,Yoshino K,Masuzawa M,Amoh Y,T

    更新日期:2016-11-04 00:00:00

  • The role of innate immune signals in antitumor immunity.

    abstract::Innate immunity serves as a first line of defense against infectious agents, and germ-line-encoded pattern recognition receptors detect stressed and infected cells and elicit potent effector activities that accomplish efficient microbe containment. Recent evidence demonstrates that these pattern-sensing systems are al...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.1.2.18495

    authors: Jinushi M

    更新日期:2012-03-01 00:00:00

  • HLA ligandomics identifies histone deacetylase 1 as target for ovarian cancer immunotherapy.

    abstract::The recent approval of clincially effective immune checkpoint inhibitors illustrates the potential of cancer immunotherapy. A challenging task remains the identification of specific targets guiding immunotherapy. Facilitated by technical advances, the direct identification of physiologically relevant targets is enable...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1065369

    authors: Peper JK,Bösmüller HC,Schuster H,Gückel B,Hörzer H,Roehle K,Schäfer R,Wagner P,Rammensee HG,Stevanović S,Fend F,Staebler A

    更新日期:2015-07-01 00:00:00

  • Glycan-mediated modification of the immune response.

    abstract::Aberrantly glycosylated tumor antigens represent promising targets for the development of anti-cancer vaccines, yet how glycans influence immune responses is poorly understood. Recent studies have demonstrated that GalNAc-glycosylation enhances antigen uptake by dendritic cells as well as CD4+ T-cell and humoral respo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.23659

    authors: Madsen CB,Pedersen AE,Wandall HH

    更新日期:2013-04-01 00:00:00

  • Spillage of bacterial products during colon surgery increases the risk of liver metastases development in a rat colon carcinoma model.

    abstract::Surgical resection of the primary tumor provides the best chance of cure for patients with colorectal carcinoma (CRC). However, bacterial translocation during intestinal surgery has been correlated with poor long-term oncological outcome. Therefore, we investigated the influence of bacterial contamination during colon...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1461302

    authors: Grewal S,Korthouwer R,Bögels M,Braster R,Heemskerk N,Budding AE,Pouw SM,van Horssen J,Ankersmit M,Meijerink J,van den Tol P,Oosterling S,Bonjer J,Gül N,van Egmond M

    更新日期:2018-07-26 00:00:00

  • Immune independent crosstalk between lymphoma and myeloid suppressor CD14+HLA-DRlow/neg monocytes mediates chemotherapy resistance.

    abstract::We have previously reported a novel phenotype of myeloid suppressors in lymphoma patients characterized by a loss of HLA-DR expression on monocytes, CD14+HLA-DRlow/neg. These cells were directly immunosuppressive and were associated with poor clinical outcome. In this study, we found that lymphoma tumors could have mo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2014.996470

    authors: Zhang ZJ,Bulur PA,Dogan A,Gastineau DA,Dietz AB,Lin Y

    更新日期:2015-01-26 00:00:00

  • In situ loading of skin dendritic cells with apoptotic bleb-derived antigens for the induction of tumor-directed immunity.

    abstract::The generation and loading of dendritic cells (DC) ex-vivo for tumor vaccination purposes is laborious and costly. Direct intradermal (i.d.) administration of tumor-associated antigens could be an attractive alternative approach, provided that efficient uptake and cross-presentation by appropriately activated skin DCs...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.946360

    authors: Ruben JM,Bontkes HJ,Westers TM,Hooijberg E,Ossenkoppele GJ,van de Loosdrecht AA,de Gruijl TD

    更新日期:2014-07-03 00:00:00

  • Immune cells in pancreatic cancer: Joining the dark side.

    abstract::Pancreatic tumors are rich in immune cell infiltrates that include CD4+ T-cell subsets encompassing both regulatory T cells and TH17 cells. Rather than protecting the organism by exerting an anticancer effect, these T-cell subsets promote tumor formation. Thus, re-activation of antitumor immunity should be investigate...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.29125

    authors: Zhang Y,McAllister F,Pasca di Magliano M

    更新日期:2014-06-05 00:00:00

  • HER2/neu DNA vaccination by intradermal gene delivery in a mouse tumor model: Gene gun is superior to jet injector in inducing CTL responses and protective immunity.

    abstract::DNA vaccines are potential tools for the induction of immune responses against both infectious disease and cancer. The dermal application of DNA vaccines is of particular interest since the epidermal and dermal layers of the skin are characterized by an abundance of antigen-presenting cells (APCs). The aim of our stud...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.22563

    authors: Nguyen-Hoai T,Kobelt D,Hohn O,Vu MD,Schlag PM,Dörken B,Norley S,Lipp M,Walther W,Pezzutto A,Westermann J

    更新日期:2012-12-01 00:00:00

  • Targeted overexpression of prostacyclin synthase inhibits lung tumor progression by recruiting CD4+ T lymphocytes in tumors that express MHC class II.

    abstract::Lung-specific overexpression of prostacyclin synthase (PGIS) decreases tumor initiation in murine lung cancer models. Prostacyclin analogs prevent lung tumor formation in mice and reverse bronchial dysplasia in former smokers. However, the effect of prostacyclin on lung cancer progression has not been well studied. We...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1423182

    authors: Li HY,McSharry M,Walker D,Johnson A,Kwak J,Bullock B,Neuwelt A,Poczobutt JM,Sippel TR,Keith RL,Weiser-Evans MCM,Clambey E,Nemenoff RA

    更新日期:2018-02-13 00:00:00

  • ATM activation mediates anticancer immunosurveillance by natural killer and T cells.

    abstract::The DNA damage response (DDR), which is frequently activated in cancer cells, has been proposed to operate as an early barrier against oncogenesis. We have recently shown that ATM mediates the spontaneous regression of Eμ-myc-driven murine B-cell leukemia in a natural killer and T cell-dependent manner. The DDR partia...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.24438

    authors: Tang ML,Gasser S

    更新日期:2013-06-01 00:00:00

  • Cross-talk within the tumor microenvironment mediates Th2-type inflammation in pancreatic cancer.

    abstract::Th2-type inflammation has been proposed to facilitate tumor growth. In De Monte et al. (J Exp Med 208:469-478, 2011) we identify in pancreatic cancer a complex cytokine/chemokine cross-talk within the tumor microenvironment mediating Th2 immune-deviation and show that the ratio of Th2/Th1 tumor infiltrating lymphocyte...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.1.1.17939

    authors: Protti MP,De Monte L

    更新日期:2012-01-01 00:00:00

  • Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human RHOA with p.Gly17Val mutation.

    abstract::A missense mutation in RHOA encoding p.Gly17 Val has been reported to occur frequently in angioimmunoblastic T-cell lymphoma (AITL). Here, we describe a murine model which expresses the human RHOA mutant gene product in a T-cell specific manner and develops AITL-like symptoms. Most transgenic mice feature with latency...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2020.1746553

    authors: Lee GJ,Jun Y,Yoo HY,Jeon YK,Lee D,Lee S,Kim J

    更新日期:2020-05-13 00:00:00

  • Human CD4- invariant NKT lymphocytes regulate graft versus host disease.

    abstract::Despite increasing evidence for a protective role of invariant (i) NKT cells in the control of graft-versus-host disease (GVHD), the mechanisms underpinning regulation of the allogeneic immune response in humans are not known. In this study, we evaluated the distinct effects of human in vitro expanded and flow-sorted ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1470735

    authors: Coman T,Rossignol J,D'Aveni M,Fabiani B,Dussiot M,Rignault R,Babdor J,Bouillé M,Herbelin A,Coté F,Moura IC,Hermine O,Rubio MT

    更新日期:2018-08-23 00:00:00

  • Trial watch: Tumor-targeting monoclonal antibodies for oncological indications.

    abstract::An expanding panel of monoclonal antibodies (mAbs) that specifically target malignant cells or intercept trophic factors delivered by the tumor stroma is now available for cancer therapy. These mAbs can exert direct antiproliferative/cytotoxic effects as they inhibit pro-survival signal transduction cascades or activa...

    journal_title:Oncoimmunology

    pub_type: 评审

    doi:10.4161/2162402X.2014.985940

    authors: Vacchelli E,Pol J,Bloy N,Eggermont A,Cremer I,Fridman WH,Galon J,Marabelle A,Kohrt H,Zitvogel L,Kroemer G,Galluzzi L

    更新日期:2015-02-03 00:00:00

  • Intratumorally delivered formulation, INT230-6, containing potent anticancer agents induces protective T cell immunity and memory.

    abstract::The benefits of anti-cancer agents extend beyond direct tumor killing. One aspect of cell death is the potential to release antigens that initiate adaptive immune responses. Here, a diffusion enhanced formulation, INT230-6, containing potent anti-cancer cytotoxic agents, was administered intratumorally into large (app...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1625687

    authors: Bloom AC,Bender LH,Tiwary S,Pasquet L,Clark K,Jiang T,Xia Z,Morales-Kastresana A,Jones JC,Walters I,Terabe M,Berzofsky JA

    更新日期:2019-07-16 00:00:00

  • Correlation between previous treatment with BRAF inhibitors and clinical response to pembrolizumab in patients with advanced melanoma.

    abstract::The optimal sequencing of targeted treatment and immunotherapy in the treatment of advanced melanoma is a key question and prospective studies to address this are ongoing. Previous observations suggest that treating first with targeted therapy may select for more aggressive disease, meaning that patients may not gain ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1283462

    authors: Simeone E,Grimaldi AM,Festino L,Giannarelli D,Vanella V,Palla M,Curvietto M,Esposito A,Palmieri G,Mozzillo N,Ascierto PA

    更新日期:2017-01-19 00:00:00

  • Order of administration of combination cytokine therapies can decouple toxicity from efficacy in syngeneic mouse tumor models.

    abstract::In combination cancer immunotherapies, consideration should be given to designing treatment schedules that harmonize with the immune system's natural timing. An efficacious temporally programmed combination therapy of extended half-life interleukin 2 (eIL2), tumor targeting antibody, and interferon (IFN) α was recentl...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1558678

    authors: Rothschilds A,Tzeng A,Mehta NK,Moynihan KD,Irvine DJ,Wittrup KD

    更新日期:2019-02-19 00:00:00

  • Replenish the source within: Rescuing tumor-infiltrating lymphocytes by double checkpoint blockade.

    abstract::We have recently reported that the PD-1 and CTLA4 signaling pathways are active in both effector and regulatory T cells, causing profound immune dysfunctions in the tumor microenvironment. In line with this notion, the dual blockade of PD-1- and CTLA4-conveyed signals may exert robust therapeutic effects. Here, we dis...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.25912

    authors: Duraiswamy J,Freeman G,Coukos G

    更新日期:2013-10-01 00:00:00

  • Anti-GD2 antibody 3F8 and barley-derived (1 → 3),(1 → 4)-β-D-glucan: A Phase I study in patients with chemoresistant neuroblastoma.

    abstract::β-glucans are complex, naturally-occurring polysaccharides that prime leukocyte dectin and complement receptor 3. Based on our preclinical findings, indicating that oral barley-derived (1 → 3),(1 → 4)-β-D-glucan (BG) synergizes with the murine anti-GD2 antibody 3F8 against neuroblastoma, we conducted a Phase I clinica...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.23402

    authors: Modak S,Kushner BH,Kramer K,Vickers A,Cheung IY,Cheung NK

    更新日期:2013-03-01 00:00:00

  • Novel treatment strategy with autologous activated and expanded natural killer cells plus anti-myeloma drugs for multiple myeloma.

    abstract::This proof-of-concept single-arm open-label phase I clinical trial (NCT02481934) studied the safety and efficacy of multiple infusions of activated and expanded natural killer (NKAE) cells in combination with anti-myeloma drugs in multiple myeloma patients. It included five patients with relapsed or refractory MM who ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1250051

    authors: Leivas A,Perez-Martinez A,Blanchard MJ,Martín-Clavero E,Fernández L,Lahuerta JJ,Martinez-Lopez J

    更新日期:2016-11-22 00:00:00

  • Immunogenic cell death in a combined synergic gene- and immune-therapy against cancer.

    abstract::It was previously demonstrated that engineered mesenchymal stem cells (MSCs) which express a high level of a very efficient modified gene CYP2B6* (CYP2B6TM-RED) acting as a suicide gene (MSC-2B6*) in combination with cyclophosphamide (CPA) constitute a powerful cell/gene therapy approach for solid tumors. In murine mo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1667743

    authors: Nayagom B,Amara I,Habiballah M,Amrouche F,Beaune P,de Waziers I

    更新日期:2019-09-27 00:00:00

  • Primary sterile necrotic cells fail to cross-prime CD8(+) T cells.

    abstract::Necrotic cells are known to activate the innate immune system and trigger inflammation by releasing damage associated molecular patterns (DAMPs). However, how necrotic cells influence the induction of antigen-specific CD8(+) T cell-mediated adaptive immune responses under sterile conditions, in the absence of pathogen...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21098

    authors: Gamrekelashvili J,Ormandy LA,Heimesaat MM,Kirschning CJ,Manns MP,Korangy F,Greten TF

    更新日期:2012-10-01 00:00:00

  • Bcl-2: Live and let die.

    abstract::Recent findings from our laboratory provide the first indication that overexpression of Bcl-2 in Eµ-myc transgenic cells enhances tumor immunosurveillance by inducing NKG2D ligands. Initial evidence suggests that this model is relevant to human patients. Thus, antitumor therapies that target Bcl-2 harbor the risk of r...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.19536

    authors: Putz EM,Schuster C,Sexl V

    更新日期:2012-08-01 00:00:00

  • Cell-to-cell distances between tumor-infiltrating inflammatory cells have the potential to distinguish functionally active from suppressed inflammatory cells.

    abstract::Beyond their mere presence, the distribution pattern of inflammatory cells is of special interest. Our hypothesis was that random distribution may be a clear indicator of being non-functional as a consequence of lack of interaction. Here, we have assessed the implication of cell-to-cell distances among inflammatory ce...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1127494

    authors: Nagl S,Haas M,Lahmer G,Büttner-Herold M,Grabenbauer GG,Fietkau R,Distel LV

    更新日期:2016-01-13 00:00:00

  • Immunoglobulin genes implicated in glioma risk.

    abstract::Both genetic and environmental factors are thought to be causal in gliomagenesis. Several genes have been implicated in glioma development, but the putative role of a major immunity-related gene complex member, immunoglobulin heavy chain γ (IGHG) has not been evaluated. Prior observations that IGHG-encoded γ marker (G...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.28609

    authors: Pandey JP,Kaur N,Costa S,Amorim J,Nabico R,Linhares P,Vaz R,Viana-Pereira M,Reis RM

    更新日期:2014-05-23 00:00:00

  • Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma.

    abstract::Efforts to reduce immunosuppression in the solid tumor microenvironment by blocking the recruitment or polarization of tumor associated macrophages (TAM), or myeloid derived suppressor cells (MDSCs), have gained momentum in recent years. Expanding our knowledge of the immune cell types, cytokines, or recruitment facto...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1507668

    authors: Moyes KW,Davis A,Hoglund V,Haberthur K,Lieberman NA,Kreuser SA,Deutsch GH,Franco S,Locke D,Carleton MO,Gilbertson DG,Simmons R,Winter C,Silber J,Gonzalez-Cuyar LF,Ellenbogen RG,Crane CA

    更新日期:2018-08-27 00:00:00

  • Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer.

    abstract::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, ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1380764

    authors: Priceman SJ,Gerdts EA,Tilakawardane D,Kennewick KT,Murad JP,Park AK,Jeang B,Yamaguchi Y,Yang X,Urak R,Weng L,Chang WC,Wright S,Pal S,Reiter RE,Wu AM,Brown CE,Forman SJ

    更新日期:2017-10-16 00:00:00

  • Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4 blockade in patients with metastatic melanoma.

    abstract::We report long-term clinical outcomes and immune responses observed from a phase 1 trial of agonist CD40 monoclonal antibody (mAb) and blocking CTLA-4 mAb in patients with metastatic melanoma. Twenty-four patients previously untreated with checkpoint blockade were enrolled. The agonistic CD40 mAb CP-870,893 and the CT...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1468956

    authors: Bajor DL,Mick R,Riese MJ,Huang AC,Sullivan B,Richman LP,Torigian DA,George SM,Stelekati E,Chen F,Melenhorst JJ,Lacey SF,Xu X,Wherry EJ,Gangadhar TC,Amaravadi RK,Schuchter LM,Vonderheide RH

    更新日期:2018-08-20 00:00:00