INSER M

Dijon, France
Dijon, France

Time filter

Source Type

Vacchelli E.,Institute Gustave Roussy | Vacchelli E.,University Paris - Sud | Eggermont A.,University Paris - Sud | Fridman C.S.,University of Paris Descartes | And 7 more authors.
OncoImmunology | Year: 2013

Oncolytic virotherapy is emerging as a promising approach for the treatment of several neoplasms. The term "oncolytic viruses" is generally employed to indicate naturally occurring or genetically engineered attenuated viral particles that cause the demise of malignant cells while sparing their nontransformed counterparts. From a conceptual standpoint, oncolytic viruses differ from so-called "oncotropic viruses" in that only the former are able to kill cancer cells, even though both display a preferential tropism for malignant tissues. Of note, such a specificity can originate at several different steps of the viral cycle, including the entry of virions (transductional specificity) as well as their intracellular survival and replication (post-transcriptional and transcriptional specificity). During the past two decades, a large array of replication-competent and replication-incompetent oncolytic viruses has been developed and engineered to express gene products that would specifically promote the death of infected (cancer) cells. However, contrarily to long-standing beliefs, the antineoplastic activity of oncolytic viruses is not a mere consequence of the cytopathic effect, i.e., the lethal outcome of an intense, productive viral infection, but rather involves the elicitation of an antitumor immune response. In line with this notion, oncolytic viruses genetically modified to drive the local production of immunostimulatory cytokines exert more robust therapeutic effects than their non-engineered counterparts. Moreover, the efficacy of oncolytic virotherapy is significantly improved by some extent of initial immunosuppression (facilitating viral replication and spread) followed by the administration of immunostimulatory molecules (boosting antitumor immune responses). In this Trial Watch, we will discuss the results of recent clinical trials that have evaluated/are evaluating the safety and antineoplastic potential of oncolytic virotherapy. © 2013 Landes Bioscience.


Vacchelli E.,Institute Gustave Roussy | Vacchelli E.,University Paris - Sud | Eggermont A.,University Paris - Sud | Saute;s-Fridman C.,University of Paris Descartes | And 8 more authors.
OncoImmunology | Year: 2013

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 criticalrole in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovisthat operates as a mixed TLR2/ TLR4 agonist; monophosphoryl lipid A (MPL), a derivative of Salmonellaminnesota that functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the August and September issues of OncoImmunology, we described the main biological features of TLRs and discussed the progress of clinical studies evaluating the safety and therapeutic potential of TLR agonists in cancer patients. Here, we summarize the latest developments in this exciting area of research, focusing on preclinical studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate the antineoplasticactivity of TLR agonists © 2013 Landes Bioscience. © 2013 Landes Bioscience.


Vacchelli E.,Institute Gustave Roussy | Vacchelli E.,University Paris - Sud | Eggermont A.,University Paris - Sud | Fridman W.H.,University of Paris Descartes | And 10 more authors.
OncoImmunology | Year: 2013

During the past two decades, the notion that cancer would merely constitute a cell-intrinsic disease has gradually been complemented by a model postulating that the immune system plays a relevant role during all stages of oncogenesis and tumor progression. Along with this conceptual shift, several strategies have been devised to stimulate tumorspecific immune responses, including relatively unselective approaches such as the systemic administration of adjuvants or immunomodulatory cytokines. One year ago, in the July issue of OncoImmunology, we described the main biological features of this large group of proteins and discussed the progress of ongoing clinical studies evaluating their safety and therapeutic potential in cancer patients. Here, we summarize the latest developments in this area of clinical research, focusing on high impact studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate which cytokines can be employed as safe and efficient immunostimulatory interventions against cancer. © 2013 Landes Bioscience.


Vacchelli E.,Institute Gustave Roussy | Vacchelli E.,University Paris - Sud | Eggermont A.,University Paris - Sud | Fridman W.H.,University of Paris Descartes | And 7 more authors.
OncoImmunology | Year: 2013

Adoptive cell transfer (ACT) represents a prominent form of immunotherapy against malignant diseases. ACT is conceptually distinct from dendritic cell-based approaches (which de facto constitute cellular vaccines) and allogeneic transplantation (which can be employed for the therapy of hematopoietic tumors) as it involves the isolation of autologous lymphocytes exhibiting antitumor activity, their expansion/activation ex vivo and their reintroduction into the patient. Re-infusion is most often performed in the context of lymphodepleting regimens (to minimize immunosuppression by host cells) and combined with immunostimulatory interventions, such as the administration of Toll-like receptor agonists. Autologous cells that are suitable for ACT protocols can be isolated from tumor-infiltrating lymphocytes or generated by engineering their circulating counterparts for the expression of transgenic tumor-specific T-cell receptors. Importantly, lymphocytes can be genetically modified prior to re-infusion for increasing their persistence in vivo, boosting antitumor responses and minimizing side effects. Moreover, recent data indicate that exhausted antitumor T lymphocytes may be rejuvenated in vitro by exposing them to specific cytokine cocktails, a strategy that might considerably improve the clinical success of ACT. Following up the Trial Watch that we published on this topic in the third issue of OncoImmunology (May 2012), here we summarize the latest developments in ACT-related research, covering both high-impact studies that have been published during the last 13 months and clinical trials that have been initiated in the same period to assess the antineoplastic profile of this form of cellular immunotherapy. © 2013 Landes Bioscience.


Ma Y.,University of Paris Descartes | Adjemian S.,Gustave Roussy Cancer Campus | Galluzzi L.,University of Paris Descartes | Zitvogel L.,INSER M | And 2 more authors.
OncoImmunology | Year: 2014

Depending on tumor type, stage and immunological contexture, the inhibition of chemokines or their receptors may yield positive or deleterious effects on disease progression. We have recently demonstrated in several murine models of anthracycline-based chemotherapy that the inhibition of chemokine (C-C motif) ligand 2 (CCL2) or chemokine (C-C motif) receptor 2 (CCR2) may impair the elicitation of anticancer immune responses that contribute to therapeutic success. © 2014 Landes Bioscience.


Aranda F.,Gustave Roussy | Vacchelli E.,Gustave Roussy | Vacchelli E.,University Paris - Sud | Eggermont A.,Gustave Roussy | And 8 more authors.
OncoImmunology | Year: 2014

Immunostimulatory monoclonal antibodies (mAbs) exert antineoplastic effects by eliciting a novel or reinstating a pre-existing antitumor immune response. Most often, immunostimulatory mAbs activate T lymphocytes or natural killer (NK) cells by inhibiting immunosuppressive receptors, such as cytotoxic T lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1 (PDCD1, best known as PD-1), or by engaging co-stimulatory receptors, like CD40, tumor necrosis factor receptor superfamily, member 4 (TNFRSF4, best known as OX40) or TNFRSF18 (best known as GITR). The CTLA4-targeting mAb ipilimumab has been approved by the US Food and Drug Administration for use in patients with unresectable or metastatic melanoma in 2011. The therapeutic profile of ipilimumab other CTLA4-blocking mAbs, such as tremelimumab, is currently being assessed in subjects affected by a large panel of solid neoplasms. In the last few years, promising clinical results have also been obtained with nivolumab, a PD-1-targeting mAb formerly known as BMS- 936558. Accordingly, the safety and efficacy of nivolumab and other PD-1-blocking molecules are being actively investigated. Finally, various clinical trials are underway to test the therapeutic potential of OX40- and GITR-activating mAbs. Here, we summarize recent findings on the therapeutic profile of immunostimulatory mAbs and discuss clinical trials that have been launched in the last 14 months to assess the therapeutic profile of these immunotherapeutic agents. © 2014 Landes Bioscience.


Semeraro M.,Gustave Roussy | Vacchelli E.,Gustave Roussy | Vacchelli E.,University Paris - Sud | Eggermont A.,Gustave Roussy | And 7 more authors.
OncoImmunology | Year: 2013

Lenalidomide is a synthetic derivative of thalidomide currently approved by the US Food and Drug Administration for use in patients affected by multiple myeloma (in combination with dexamethasone) and low or intermediate-1 risk myelodysplastic syndromes that harbor 5q cytogenetic abnormalities. For illustrative purposes, the mechanism of action of lenalidomide can be subdivided into a cancer cellintrinsic, a stromal, and an immunological component. Indeed, lenalidomide not only exerts direct cell cycle-arresting and proapoptotic effects on malignant cells, but also inhi their physical and functional interaction with the tumor microenvironment and mediates a robust, pleiotropic immunostimulatory activity. In particular, lenalidomide has been shown to stimulate the cytotoxic functions of T lymphocytes and natural killer cells, to limit the immunosuppressive impact of regulatory T cells, and to modulate the secretion of a wide range of cytokines, including tumor necrosis factor α, interferon γ as well as interleukin (IL)-6, IL-10, and IL-12. Throughout the last decade, the antineoplastic and immunostimulatory potential of lenalidomide has been investigated in patients affected by a wide variety of hematological and solid malignancies. Here, we discuss the results of these studies and review the status of clinical trials currently assessing the safety and efficacy of this potent immunomodulatory drug in oncological indications. © 2013 Landes Bioscience.


Hervieu A.,INSER M | Hervieu A.,Dijon CHU Hospital | Hervieu A.,University of Burgundy | Mignot G.,INSER M | And 3 more authors.
OncoImmunology | Year: 2013

Melanoma is a highly chemoresistant and metastatic tumor that, in the absence of BRAF mutations, is generally treated with the alkylating agent dacarbazine (DTIC). We discovered that DTIC upregulates the expression of NKG2D ligands on tumor cells, leading to the activation of natural killer (NK) and CD8+ T cells. These observations underscore the immunogenic properties of DTIC and provide a rationale to combine DTIC with immunotherapeutic agents © 2013 Landes Bioscience.


Mignot G.,INSER M | Mignot G.,University of Burgundy | Bugaut H.,INSER M | Bugaut H.,University of Burgundy | And 3 more authors.
OncoImmunology | Year: 2013

In addition to cytotoxic effects, anticancer agents can exert multiple immunomodulatory functions. We have recently described the molecular mechanisms whereby bleomycin can (1) promote endoplasmic reticulum stress, causing the immunogenic death of cancer cells and hence strengthening antitumor CD8+ T cell responses; and (2) induce the secretion of transforming growth factor β (TGFβ), which stimulates regulatory T cells. This suggests that bleomycin may be favorably combined with TGFβ-targeting strategies. © 2013 Landes Bioscience.


Ghiringhelli F.,INSER M | Ghiringhelli F.,Center Georges Francois Leclerc | Ghiringhelli F.,University of Burgundy | Bruchard M.,INSER M | And 4 more authors.
OncoImmunology | Year: 2013

Cytotoxic anticancer drugs can promote antitumor immune responses. The anticancer activity of 5-fluorouracil (5FU)relies on the restorationof T-cell immunity following the elimination of myeloid-derived suppressor cells (MDSCs). We have recently discovered that the 5FU-driven activation of the NLRP3 inflammasome in MDSCs promotes tumorangiogenesis by eliciting TH17 responses that compromise anticancer immunity. This underscores the need to combine5-FU with NLRP3 inhibitors to prevent tumor progression. © 2013 Landes Bioscience.

Loading INSER M collaborators
Loading INSER M collaborators