Last update 01 Nov 2024

IL-2R x EpCAM

Last update 01 Nov 2024

Basic Info

Related Targets

IL-2REpCAM

Drugs associated with IL-2R x EpCAM

Tucotuzumab celmoleukin

Target

EpCAM x IL-2R

Mechanism

EpCAM inhibitors [+1]

Active Org.-

Originator Org.

EMD Lexigen Research Center Corp.

Active Indication-

Inactive Indication

Bladder Cancer [+8]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with IL-2R x EpCAM

EUCTR2006-004566-13-DE / Not yet recruitingNot Applicable

An open-label, randomised, phase II study in subjects with extensive disease, small cell lung cancer (ED-SCLC) after an initial response (complete response or partial response) to platinum-based therapy to determine the effect of EMD 273066 following low-dose cyclophosphamide on disease progression and survival versus best supportive care alone.

Start Date26 Mar 2008

Sponsor / Collaborator

Merck KGaA

NCT00408967 / WithdrawnPhase 2

An Open-label Phase II Study of Two Dose Levels of EMD 273066 Administered With Low-dose Cyclophosphamide Following Objective Response to Second-line Chemotherapy in Women With Recurrent Ovarian Carcinoma

The purpose of this study is to determine if either of two doses of EMD 273066 when given with a low dose of cyclophosphamide will result in a second time to progression that is as long or longer than the first time to progression

Start Date31 Dec 2006

Sponsor / Collaborator

EMD Serono, Inc.

100 Clinical Results associated with IL-2R x EpCAM

100 Translational Medicine associated with IL-2R x EpCAM

0 Patents (Medical) associated with IL-2R x EpCAM

Literatures (Medical) associated with IL-2R x EpCAM

01 Jul 2019·Oral OncologyQ2 · MEDICINE

Surrogates of immunologic cell death (ICD) and chemoradiotherapy outcomes in head and neck squamous cell carcinoma (HNSCC)

Q2 · MEDICINE

Article

Author: Kotsantis, Ioannis ; Anastasiou, Maria ; Koutsodontis, George ; Lianidou, Evi ; Economopoulou, Panagiota ; Giotakis, Evangelos ; Vagia, Elena ; Psyrri, Amanda ; Gagari, Eleni ; Kavourakis, George ; Gkotzamanidou, Maria ; Maragoudakis, Pavlos ; Strati, Areti ; Kirodimos, Efthymios ; Prikas, Constantine ; Perisanidis, Christos ; Papadimitriou, Nikolaos

OBJECTIVESChemoradiation can induce immunogenic (ICD) or tolerogenic cell death. ICD relies on the generation of damage-associated molecular patterns which can stimulate toll-like receptors (TLRs). We sought to determine whether we can predict responses to chemoradiation by measuring surrogate biomarkers of ICD in a cohort of patients with locally advanced (LA) head and neck squamous cell carcinoma (HNSCC).MATERIALS AND METHODSIn a cohort of 113 LA HNSCC pts we evaluated expression of TLR4, TLR7 and TLR9 in the EpCAM + circulating tumor cell (CTC) fraction at baseline and after cisplatin chemoradiation. We also quantified changes in chemokines CXCL10, CXCL16 and IL-2R in the serum.RESULTSSeventy three patients had evaluable specimens. Among cases with biomarker assessment at baseline and post treatment, 36.8% had an increase in CXCL10 levels (p = 0.022), 73.7% had an increase in CXCL16 levels (p = 0.002) and 63.8% had an increase in IL2Ra levels (p = 0.032) with treatment. 52.0% of evaluable cases at baseline and post-treatment had an increase in TLR4 levels (p = 0.996), 42.9% had an increase in TLR7 levels (p = 0.042) and 27.7% had increase in TLR9 levels (p = 0.011) with treatment. CXCL10 levels at baseline were significantly associated with PFS and OS (p = 0.010 and p = 0.032, respectively).CONCLUSIONSOur results suggest that chemoradiation leads to quantifiable effects in surrogate markers of ICD. These effects may inform trials combining chemoradiation with immune checkpoint inhibitors. In addition, CXCL10 has prognostic effect in pts treated with chemoradiation.

01 Dec 2011·Cancer Immunology, ImmunotherapyQ2 · MEDICINE

Ab-IL2 fusion proteins mediate NK cell immune synapse formation by polarizing CD25 to the target cell-effector cell interface

Q2 · MEDICINE

Article

Author: Paul M. Sondel ; Brian Gadbaw ; Stephen D. Gillies ; Arvinder K. Kapur ; Manish S. Patankar ; Sachi Horibata ; Dhara Patel ; Joseph Connor ; Jennifer A. A. Gubbels ; Ilia N. Buhtoiarov ; Jacquelyn A. Hank

The huKS-IL2 immunocytokine (IC) consists of IL2 fused to a mAb against EpCAM, while the hu14.18-IL2 IC recognizes the GD2 disialoganglioside. They are under evaluation for treatment of EpCAM(+) (ovarian) and GD2(+) (neuroblastoma and melanoma) malignancies because of their proven ability to enhance tumor cell killing by antibody-dependent cell-mediated cytotoxicity (ADCC) and by antitumor cytotoxic T cells. Here, we demonstrate that huKS-IL2 and hu14.18-IL2 bind to tumor cells via their antibody components and increase adhesion and activating immune synapse (AIS) formation with NK cells by engaging the immune cells' IL-2 receptors (IL2R). The NK leukemia cell line, NKL (which expresses high affinity IL2Rs), shows fivefold increase in binding to tumor targets when treated with IC compared to matching controls. This increase in binding is effectively inhibited by blocking antibodies against CD25, the α-chain of the IL2R. NK cells isolated from the peritoneal environment of ovarian cancer patients, known to be impaired in mediating ADCC, bind to huKS-IL2 via CD25. The increased binding between tumor and effector cells via ICs is due to the formation of AIS that are characterized by the simultaneous polarization of LFA-1, CD2 and F-actin at the cellular interface. AIS formation of peritoneal NK and NKL cells is inhibited by anti-CD25 blocking antibody and is 50-200% higher with IC versus the parent antibody. These findings demonstrate that the IL-2 component of the IC allows IL2Rs to function not only as receptors for this cytokine but also as facilitators of peritoneal NK cell binding to IC-coated tumor cells.

01 Aug 2003·Clinical cancer research : an official journal of the American Association for Cancer Research

Sensitive and specific detection of circulating cancer cells in patients with hepatocellular carcinoma; detection of human telomerase reverse transcriptase messenger RNA after immunomagnetic separation.

Article

Author: Fukuhara, Yasuo ; Suda, Takeshi ; Aoyagi, Yutaka ; Nomoto, Minoru ; Waguri, Nobuo ; Mita, Yusaku ; Kobayashi, Makoto ; Igarashi, Masato ; Kuroiwa, Takashi ; Kawai, Hirokazu

PURPOSEWe evaluated whether detection of human telomerase reverse transcriptase (hTERT) mRNA after immunomagnetic separation is useful to detect circulating cancer (CC) cells.EXPERIMENTAL DESIGNTwo ml of peripheral blood were collected from 55 cases with hepatocellular carcinoma (HCC), 20 cases with chronic liver diseases devoid of cancer, and 20 healthy volunteers. Then 1500 and 500 micro l were subjected to immunomagnetic separations using Ber-EP4 and anti-CD45 antibodies, harvested and supernatant cells were collected as epithelial and nonleukocyte fractions, respectively. Samples of each fraction were subjected to reverse transcription-PCR detecting beta-actin, interleukin-2 receptor (IL-2r), alpha-fetoprotein, and hTERT mRNAs. The cases were judged to be positive, equivocal, or negative for CC cells when hTERT positivity with IL-2r negativity, hTERT positivity with IL-2r positivity, or hTERT negativity was seen in epithelial and/or nonleukocyte fractions, respectively.RESULTSThe dilution experiments revealed that our system could detect 10(0-1) HeLa cells involved in 2 ml of blood. The Ber-EP4-harvested cells from cases with distant metastasis were positive for immunostaining using Hep Par 1 monoclonal antibody. CC cells were judged to be positive in 29 of 55 (53%) HCC cases. On the contrary, no cases without HCC were determined to be positive. The frequency of positivity was significantly correlated with disease extent of HCC.CONCLUSIONSThese results strongly suggest that detection of hTERT mRNA after immunomagnetic separation is a specific and sensitive tool to detect CC cells and that it would provide useful source for further investigation of cancer metastasis.

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