Anticancer immunochemotherapy using adjuvants with direct cytotoxic effects

Zitvogel, Laurence; Kroemer, Guido

doi:10.1172/jci39991

Cited by 42 publications

(56 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…243 RIG-I antagonists may thus also be suited for treatment of viral infections and cancer. 244 A recent study has identified an RNA aptamer that binds to RIG-I, activates signaling, and blocks viral replication in infected host cells, demonstrating potential as an antiviral agent 245 and possibly also as an anti-cancer drug.…”

Section: Rna Helicases As Drug Targetsmentioning

confidence: 99%

RNA helicases in infection and disease

Steimer

Klostermeier

2012

RNA Biology

View full text Add to dashboard Cite

Section: Rna Helicases As Drug Targetsmentioning

confidence: 99%

RNA helicases in infection and disease

Steimer

Klostermeier

2012

RNA Biology

View full text Add to dashboard Cite

“…Recently, it has become evident that chemotherapeutic drugs not only have a direct cytotoxic effect on tumor cells but may also potentiate the immune system via so-called off-target effects (1,2). For example, direct immune-activating effects of cancer chemotherapy have been observed: treatment with low concentrations of several chemotherapeutics resulted in increased antigen cross-presentation, T lymphocyte expansion, and T cell infiltration of tumors by to-date-unknown molecular mechanisms (3,4).…”

Section: Introductionmentioning

confidence: 99%

Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice

Lesterhuis

Punt²,

Hato³

et al. 2011

J. Clin. Invest.

289

226

View full text Add to dashboard Cite

Tumor microenvironments feature immune inhibitory mechanisms that prevent T cells from generating effective antitumor immune responses. Therapeutic interventions aimed at disrupting these inhibitory mechanisms have been shown to enhance antitumor immunity, but they lack direct cytotoxic effects. Here, we investigated the effect of cytotoxic cancer chemotherapeutics on immune inhibitory pathways. We observed that exposure to platinum-

show abstract

“…Briefly, stress before death matters for an immunogenic cell death pathway to occur. First, an endoplasmic reticulum stress response culminating with CRT exposure to the tumor cell surface (17), then late apoptosis associated with the exodus of the chromatin-binding HMGB1 protein (18), and finally, activation of the autophagy machinery leading to ATP release (19), all contribute to the adequate phagocytosis, processing, and antigen presentation of the dying tumor cells to T lymphocytes (20,21). Therefore, we addressed whether CatmAb-mediated tumor cell death could trigger an immunogenic cell death program.…”

Section: Tumor Cell Death Fingerprint Post-catmabmentioning

confidence: 99%

Potent Immunomodulatory Effects of the Trifunctional Antibody Catumaxomab

et al. 2013

Self Cite

View full text Add to dashboard Cite

Catumaxomab (CatmAb), a trifunctional bispecific antibody directed against the epithelial cell adhesion molecule (EpCAM) and the T-cell antigen CD3, is approved as intraperitoneal therapy for the treatment of malignant ascites in patients with EpCAM-positive carcinomas. The immunomonitoring results of a phase II/III study using CatmAb revealed a tumoricidal effect associated with reduced VEGF levels, CD69-expressing T cells, and the release of T-helper cell (T H )-1 cytokines. We comprehensively dissected the immunomodulatory effects of the CatmAb on the major subsets of malignant ascites-infiltrating leukocytes and the molecular fingerprint of tumor cell death. Herein we show that in the presence of EpCAM-positive tumor targets, CatmAb markedly enhanced T-cell activation [CD69, CD107A (LAMP1), HLA-DR and PD-1(PDCD1) expression] and stimulated inflammatory CD4þ T H 1 and CD8 þ T H 1 to release IFN-g but failed to trigger T H 17 cells. Engagement of CD16-expressing cells caused upregulation of TRAIL (TNFSF10) and costimulatory CD40 and CD80 molecules. CatmAb promoted tumor cell death associated with ATP release and strongly synergized with oxaliplatin for the exposure of the three hallmarks of immunogenic cell death (calreticulin, HMGB1, and ATP). These findings warrant validation as potential biomarkers of efficacy of CatmAb. Cancer Res; 73(15); 4663-73. Ó2013 AACR.

show abstract

Anticancer immunochemotherapy using adjuvants with direct cytotoxic effects

Cited by 42 publications

References 19 publications

RNA helicases in infection and disease

RNA helicases in infection and disease

Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice

Potent Immunomodulatory Effects of the Trifunctional Antibody Catumaxomab

Contact Info

Product

Resources

About