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 (approx. 300mm3) subcutaneous murine Colon26 tumors. Treatment resulted in regression from baseline in 100% of the tumors and complete response in up to 90%. CD8+ or CD8+/CD4+ T cell double-depletion at treatment onset prevented complete responses, indicating a critical role of T cells in promoting complete tumor regression. Mice with complete response were protected from subcutaneous and intravenous re-challenge of Colon26 cells in a CD4+/CD8+ dependent manner. Thus, immunological T cell memory was induced by INT230-6. Colon26 tumors express the endogenous retroviral protein gp70 containing the CD8+ T-cell AH-1 epitope. AH-1-specific CD8+ T cells were detected in peripheral blood of tumor-bearing mice and their frequency increased 14 days after treatment onset. AH-1-specific CD8+ T cells were also significantly enriched in tumors of untreated mice. These cells had an activated phenotype and highly expressed Programmed cell-death protein-1 (PD-1) but did not lead to tumor regression. CD8+ T cell tumor infiltrate also increased 11 days after treatment. INT230-6 synergized with checkpoint blockade, inducing a complete remission of the primary tumors and shrinking of untreated contralateral tumors, which demonstrates not only a local but also systemic immunological effect of the combined therapy. Similar T-cell dependent inhibition of tumor growth was also found in an orthotopic 4T1 breast cancer model.
journal_name
Oncoimmunologyjournal_title
Oncoimmunologyauthors
Bloom AC,Bender LH,Tiwary S,Pasquet L,Clark K,Jiang T,Xia Z,Morales-Kastresana A,Jones JC,Walters I,Terabe M,Berzofsky JAdoi
10.1080/2162402X.2019.1625687subject
Has Abstractpub_date
2019-07-16 00:00:00pages
e1625687issue
10eissn
2162-4011issn
2162-402Xpii
1625687journal_volume
8pub_type
杂志文章相关文献
OncoImmunology文献大全abstract::Mycosis fungoides (MF) progresses from patch to tumor stage by expansion of malignant T-cells that fail to be controlled by protective immune mechanisms. In this study, we focused on IL-32, a cytokine, highly expressed in MF lesions. Depending on the other cytokines (IL-4, GM-CSF) present during in vitro culture of he...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2016.1181237
更新日期:2016-05-05 00:00:00
abstract::The efficacy of antitumoral responses can be increased using combinatorial vaccine strategies. We recently showed that vaccination could be optimized by local administration of diverse molecular or bacterial agents to target and augment antitumoral CD8 T cells in the genital mucosa (GM) and increase regression of cerv...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1016697
更新日期:2015-05-22 00:00:00
abstract::Synthesis of extracellular adenosine by the ectonucleotidases CD39 and CD73 represents an important pathway of immune suppression in the tumor microenvironment. Using two mouse models (RET transgenic melanoma and Panc02 orthotopic pancreatic adenocarcinoma), we identified an elevated frequency of ectonucleotidase-expr...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2020.1744946
更新日期:2020-04-09 00:00:00
abstract::Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated through the IgG Fc receptor FcγRIIIa represents a major effector function of many therapeutic antibodies. In an attempt to further enhance natural killer (NK) cell-mediated ADCC, we combined therapeutic antibodies against CD20 and CD38 with recombinant immu...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1058459
更新日期:2015-06-05 00:00:00
abstract::Prostate cancer (PCa) was estimated to have the second highest global incidence rate for male non-skin tumors and is the fifth most deadly in men thus mandating the need for novel treatment options. MG1-Maraba is a potent and versatile oncolytic virus capable of lethally infecting a variety of prostatic tumor cell lin...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1445459
更新日期:2018-03-27 00:00:00
abstract::Graft-versus-host disease (GvHD) remains a significant impediment to allogeneic hematopoietic cell transplantation (HCT) success, necessitating studies focused on alleviating GvHD, while preserving the graft-versus-leukemia (GvL) effect. Based on our previous studies showing bendamustine with total body irradiation (B...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2020.1758011
更新日期:2020-04-30 00:00:00
abstract::Dendritic cell (DC)-based vaccines against cancer have been extensively developed over the past two decades. Typically DC-based cancer immunotherapy entails loading patient-derived DCs with an appropriate source of tumor-associated antigens (TAAs) and efficient DC stimulation through a so-called "maturation cocktail" ...
journal_title:Oncoimmunology
pub_type: 杂志文章,评审
doi:10.1080/2162402X.2017.1328341
更新日期:2017-05-12 00:00:00
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
更新日期:2018-09-07 00:00:00
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
更新日期:2013-12-01 00:00:00
abstract::High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs from the TransPORTE...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2016.1264565
更新日期:2016-12-09 00:00:00
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
更新日期:2018-08-20 00:00:00
abstract::Surgical resection is the mainstay of treatment for solid tumors, but the postoperative period is uniquely inclined to the formation of metastases, largely due to the suppression of natural killer (NK) cells. We found that preoperative influenza vaccination prevents postoperative NK-cell dysfunction, attenuating tumor...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.26618
更新日期:2013-11-01 00:00:00
abstract::Circulating fibrocytes were reported to represent a novel myeloid-derived suppressor cell (MDSC) subset and they were also proposed to be involved in the tumor immune escape. This novel fibrocyte subset had a surface phenotype resembling non-monocytic MDSCs (CD14-CD11chiCD123-) and exhibited immunomodulatory roles. Mo...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1034918
更新日期:2015-05-27 00:00:00
abstract::Tumors arise and progress in immunocompetent hosts presumably by activating tolerance mechanisms critical for normal homeostasis. Host immune cells can mount anti-tumor responses by activation of Toll-like receptors (TLRs). However, emerging data suggests that molecules that negatively regulate TLRs are exploited by t...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.18434
更新日期:2012-05-01 00:00:00
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
更新日期:2018-01-29 00:00:00
abstract::Oncolytic virotherapy is an emergent promising therapeutic approach for the treatment of cancer. We have constructed a vaccinia virus (WR strain) deleted for thymidine kinase (TK) and ribonucleotide reductase (RR) genes that expressed the fusion suicide gene FCU1 derived from the yeast cytosine deaminase and uracil ph...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1080414
更新日期:2015-10-06 00:00:00
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
更新日期:2014-12-21 00:00:00
abstract::Pharmacological reactivation of the p53 tumor suppressor is a promising strategy for anti-cancer therapy due to its high potential to elicit apoptosis or growth arrest in cancer cells. Recently we uncovered the mechanism of activation of the innate immune response by p53 upon its activation by small molecules. ...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.19409
更新日期:2012-07-01 00:00:00
abstract:: Background : Peritoneal carcinomatosis (PC) is a terminal evolution from primary colorectal cancer (pCRC) associated with poor patient survival. Impact of the immune cell infiltrate on PC pathogenesis is unknown. Therefore, we characterized the immunological tumor microenv...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2016.1242543
更新日期:2016-10-14 00:00:00
abstract::Gliomas are lethal brain tumors that resist standard therapeutic approaches. Immunotherapy is a promising alternative strategy mostly developed in the context of glioblastoma. However, there is a need for implementing immunotherapy for grade II/III gliomas, as these are the most common CNS tumors in young adults with ...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2017.1391972
更新日期:2017-11-07 00:00:00
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
更新日期:2013-10-01 00:00:00
abstract::Estrogen receptors have recently been demonstrated at the cell surface. Unlike nuclear receptors, they are able to trigger rapid responses inside the cells. In this study, we evaluated the presence and the possible role of autoantibodies specific to estrogen receptor (anti-ER Abs) in the peripheral blood of breast can...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1074375
更新日期:2015-08-12 00:00:00
abstract::Tumor cells expressing TLRs is generally recognized to mediate tumor inflammation. However, whether and how tumor TLR signaling pathways negatively regulate tumor inflammation remains unclear. In this report, we find that TLR4 signaling of H22 hepatocarcinoma tumor cells is transduced through MyD88 pathway to actin cy...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.19854
更新日期:2012-08-01 00:00:00
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
更新日期:2013-08-01 00:00:00
abstract::Numerous studies have demonstrated that inflammation contributes to a variety of cancer formation, among them, colitis-associated cancer (CAC) represents a typical inflammation-related cancer. Interleukin 27 (IL-27) has been demonstrated to play an important role in inflammation-related disease. The effect of IL-27 in...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2016.1268309
更新日期:2017-01-20 00:00:00
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
更新日期:2018-07-26 00:00:00
abstract::Purpose: Tumor development has been closely linked to tumor microenvironment, particularly in terms of myeloid-derived suppressive cells (MDSCs), a heterogeneous population of immature myeloid cells that protect tumors from elimination by immune cells. Approaches aimed at blocking MDSC accumulation could improve cance...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1442167
更新日期:2018-03-13 00:00:00
abstract::Objective:Ovarian cancer (OC) is often diagnosed at an advanced stage with two thirds of patients experiencing recurrent disease with a poor prognosis. Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has shown curative potential in malignant melanoma, but has only been investigated scarcely in ot...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1502905
更新日期:2018-09-26 00:00:00
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
更新日期:2012-11-01 00:00:00
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
更新日期:2015-01-26 00:00:00