The New Era of Cancer Immunotherapy

Khalil, Danny N.; Budhu, Sadna; Gasmi, Billel; Zappasodi, Roberta; Hirschhorn-Cymerman, Daniel; Plitt, Tamar; Henau, Olivier De; Zamarin, Dmitriy; Holmgaard, Rikke; Murphy, Judith T.; Wolchok, Jedd D.; Merghoub, Taha

doi:10.1016/bs.acr.2015.04.010

Cited by 43 publications

(19 citation statements)

References 376 publications

(393 reference statements)

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“…Migration and seeding of cancer cells in the lung after tail vein injection depends on the interactions of tumor cells and the resident host cells, i.e., the microenvironment [54]. Many studies have shown that the microenvironment has the capacity to eliminate, minimize or enhance tumorigenesis [55, 56] depending on its composition and the stromal cell proportions or their activation states [34, 57]. …”

Section: Discussionmentioning

confidence: 99%

Knockout of MDA-9/Syntenin (SDCBP) expression in the microenvironment dampens tumor-supporting inflammation and inhibits melanoma metastasis

et al. 2016

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Cancer development and progression to metastasis is a complex process, which largely depends on bidirectional communication between tumor cells and their microenvironment. Melanoma differentiation associated gene-9 (mda-9, also known as Syntenin-1, SDCBP), a gene first cloned by our group, is robustly expressed in multiple cancers including melanoma and contributes to invasion and metastasis in a tumor cell-intrinsic manner. However, the role of MDA-9/Syntenin in the tumor cell-extrinsic microenvironment remains unclear even though MDA-9/Syntenin is ubiquitously expressed in most organs that are active metastatic sites for melanoma, e.g., lung, lymph node, brain, and liver. In this study, we explored the effect of environmental mda-9/syntenin expression on melanoma growth and metastasis using multiple immunocompetent animal models, syngeneic B16 xenograft and intravenous B16 mouse model and a genetically engineered mouse (GEM) model of melanoma. Host-deficient expression of mda-9/syntenin in mice negatively impacted on subcutaneously implanted B16 tumor growth and lung metastasis. Absence of MDA-9/Syntenin in the lung microenvironment suppressed tumor growth by modulating in situ Interleukin 17A (IL17A) expression and impaired the recruitment of myeloid derived suppressor cells (MDSCs) and Th17 cells as compared to genetically wild type animals. Additionally, loss of mda-9/syntenin expression in a spontaneous melanoma model (melanocyte-specific pten loss and BrafV600E mutation) significantly delayed tumor initiation and suppressed metastasis to the lymph nodes and lungs. The present study highlights a novel role of mda-9/syntenin in tumor-promoting inflammation and immune suppression. These observations along with other documented roles of MDA-9/Syntenin in cancer and metastasis support the potential relevance of MDA-9/Syntenin in the carcinogenic process and as a target for developing improved therapies by using either genetic or pharmacologic approaches to treat and prevent melanoma and other cancers.

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Section: Discussionmentioning

confidence: 99%

Knockout of MDA-9/Syntenin (SDCBP) expression in the microenvironment dampens tumor-supporting inflammation and inhibits melanoma metastasis

et al. 2016

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“…Immunotherapy is an emerging field in the oncology with promising results for cancer patients [ 85 , 86 , 87 ]. The mission is to achieve lifelong immunity against the cancer in the patient, in order to eradicate the primary tumor as well as distant metastases.…”

Section: Reovirus and Immune Stimulationmentioning

confidence: 99%

Exploring Reovirus Plasticity for Improving Its Use as Oncolytic Virus

Kemp

Hoeben

Wollenberg

2015

Viruses

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Reoviruses are non-enveloped viruses with a segmented double stranded RNA genome. In humans, they are not associated with serious disease. Human reoviruses exhibit an inherent preference to replicate in tumor cells, which makes them ideally suited for use in oncolytic virotherapies. Their use as anti-cancer agent has been evaluated in several clinical trials, which revealed that intra-tumoral and systemic delivery of reoviruses are well tolerated. Despite evidence of anti-tumor effects, the efficacy of reovirus in anti-cancer monotherapy needs to be further enhanced. The opportunity to treat both the primary tumor as well as metastases makes systemic delivery a preferred administration route. Several pre-clinical studies have been conducted to address the various hurdles connected to systemic delivery of reoviruses. The majority of those studies have been done in tumor-bearing immune-deficient murine models. This thwarts studies on the impact of the contribution of the immune system to the tumor cell eradication. This review focuses on key aspects of the reovirus/host-cell interactions and the methods that are available to modify the virus to alter these interactions. These aspects are discussed with a focus on improving the reovirus’ antitumor efficacy.

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“…Over a century, immunology has been employed to treat malignant tumors, such as monoclonal antibody (mAb), bispecific antibody, tumor vaccine, immune checkpoint blockade, cytokine-induced killer (CIKs), tumor-infiltrating lymphocytes (TILs), and most recently chimeric antigen receptor T (CAR-T) [1]. Application of monoclonal antibodies (Herceptin, cetuximab) in malignant tumor patients showed a satisfying response rate.…”

Section: Introductionmentioning

confidence: 99%

Chimeric antigen receptor T cells: a novel therapy for solid tumors

et al. 2017

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The chimeric antigen receptor T (CAR-T) cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs) expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII) was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2), and mesothelin (MSLN), as well as the challenges for CAR-T cell therapy.

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The New Era of Cancer Immunotherapy

Cited by 43 publications

References 376 publications

Knockout of MDA-9/Syntenin (SDCBP) expression in the microenvironment dampens tumor-supporting inflammation and inhibits melanoma metastasis

Knockout of MDA-9/Syntenin (SDCBP) expression in the microenvironment dampens tumor-supporting inflammation and inhibits melanoma metastasis

Exploring Reovirus Plasticity for Improving Its Use as Oncolytic Virus

Chimeric antigen receptor T cells: a novel therapy for solid tumors

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