Last update 01 Nov 2024

MAGE-A3 Positive Muscle Invasive Bladder Carcinoma

Last update 01 Nov 2024

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Clinical Trials associated with MAGE-A3 Positive Muscle Invasive Bladder Carcinoma

NCT01435356 / TerminatedPhase 2IIT

A Randomized, Double Blind, Placebo Controlled Phase II Trial to Evaluate the Safety and Efficacy of recMAGE-A3 + AS15 ASCI in Patients With MAGE-A3 Positive Muscle Invasive Bladder Cancer After Cystectomy

The purpose of this clinical trial was to demonstrate the benefit of the immunotherapeutic product recMAGE-A3 + AS-15 given to patients with bladder cancer after removal of the bladder. A course of 13 injections was administered over 27 months.

Start Date01 Aug 2011

Sponsor / Collaborator

GSK Plc

NCT00706238 / TerminatedPhase 2

Study of GSK1203486A Antigen-Specific Cancer Immunotherapeutic in Patients With Unresectable and Progressive Metastatic Cutaneous Melanoma

This study is being done to evaluate the safety and the clinical activity of MAGE-A3 Antigen-Specific Cancer Immunotherapeutic in patients with unresectable and progressive metastatic cutaneous melanoma.

Start Date29 Sep 2008

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with MAGE-A3 Positive Muscle Invasive Bladder Carcinoma

100 Translational Medicine associated with MAGE-A3 Positive Muscle Invasive Bladder Carcinoma

0 Patents (Medical) associated with MAGE-A3 Positive Muscle Invasive Bladder Carcinoma

Literatures (Medical) associated with MAGE-A3 Positive Muscle Invasive Bladder Carcinoma

01 Nov 2023·Environmental Research

Novel affibody molecules as potential agents in molecular imaging for MAGE-A3-positive tumor diagnosis

Article

Author: Cheng, Kai ; Zhu, Guanbao ; Zhang, Lifang ; Jiang, Pengfei ; Ren, Jiahuan ; Cai, Yiqi ; Zhu, Shanli ; Shao, Huanyi ; Wang, Pengfei ; Jiang, Peipei ; Jin, Jinji

BACKGROUNDThe cancer-testis protein melanoma antigen A3 (MAGE-A3) is highly expressed in a broad range of malignant tumor forms. It has been confirmed that affibody molecules, a novel family of small (∼6.5 kDa) targeting proteins, are useful agents for molecular imaging and targeted tumor treatment. As a novel agent for in vivo molecular imaging detection of MAGE-A3-positive tumors, the efficacy of affibody molecules was assessed in this research.METHODSIn this study, three cycles of phage display library screening resulted in the isolation of two new affibody molecules (Z_MAGE-A3:172 and Z_MAGE-A3:770) that attach to MAGE-A3. These molecules were then expressed in bacteria and purified. The affibody molecules with high affinity and specificity were evaluated using western blotting, immunohistochemistry, indirect immunofluorescence, surface plasmon resonance, and near-infrared optical imaging of tumor-bearing nude mice.RESULTSThe selected Z_MAGE-A3 affibodies can precisely bind to the MAGE-A3 protein in living cells and display high-affinity binding to the MAGE-A3 protein at the molecular level. Furthermore, the accumulation of DyLight755-labeled Z_MAGE-A3:172 or Z_MAGE-A3:770 in MAGE-A3-positive tumors was achieved as early as 30 min and disappeared at 48 h post-injection.CONCLUSIONOur findings support the potential of the two MAGE-A3 protein-binding affibody molecules for their use as molecular imaging agents.

02 Jan 2019·OncoImmunologyQ2 · MEDICINE

Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials

Q2 · MEDICINE

ArticleOA

Author: Wan, Yonghong ; Stoll, Gautier ; McCart, J. Andrea ; El-Warrak, Alexander ; Breitbach, Caroline J. ; Pomoransky, Julia ; Acuna, Sergio A. ; Evelegh, Carole ; Yadollahi, Beta ; Tang, Nan ; Hanwell, David ; Lopez, Roberto ; Millar, Jamie ; Bramson, Jonathan L. ; Parsons, Robin ; Pol, Jonathan G. ; Bell, John C. ; Martin, Chantal G. ; Goldstein, Alyssa ; Atherton, Matthew J. ; Lichty, Brian D. ; Moloo, Badru ; Stephenson, Kyle B. ; Denisova, Galina ; Turner, Patricia V. ; LaFrance, Sandra ; Stojdl, David F.

Multiple immunotherapeutics have been approved for cancer patients, however advanced solid tumors are frequently refractory to treatment. We evaluated the safety and immunogenicity of a vaccination approach with multimodal oncolytic potential in non-human primates (NHP) (Macaca fascicularis). Primates received a replication-deficient adenoviral prime, boosted by the oncolytic Maraba MG1 rhabdovirus. Both vectors expressed the human MAGE-A3. No severe adverse events were observed. Boosting with MG1-MAGEA3 induced an expansion of hMAGE-A3-specific CD4⁺ and CD8⁺ T-cells with the latter peaking at remarkable levels and persisting for several months. T-cells reacting against epitopes fully conserved between simian and human MAGE-A3 were identified. Humoral immunity was demonstrated by the detection of circulating MAGE-A3 antibodies. These preclinical data establish the capacity for the Ad:MG1 vaccination to engage multiple effector immune cell populations without causing significant toxicity in outbred NHPs. Clinical investigations utilizing this program for the treatment of MAGE-A3-positive solid malignancies are underway (NCT02285816, NCT02879760).

01 Jan 2018·ESMO OpenQ3 · MEDICINE

Association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic

Q3 · MEDICINE

ArticleOA

Author: Robert, Caroline ; Lebbe, Céleste ; Jarnjak, Silvija ; Lehmann, Frédéric F ; Baurain, Jean-François ; Grange, Florent ; Mortier, Laurent ; De Sousa Alves, Pedro Miguel ; Louahed, Jamila ; Neyns, Bart ; Gillet, Marc ; Ulloa-Montoya, Fernando

PURPOSEThis study assessed clinical activity, safety and immunogenicity of MAGE-A3 immunotherapeutic in patients with MAGE-A3-positive metastatic melanoma.PATIENTS AND METHODSIn this open-label, multicentre, uncontrolled, Phase II study (ClinicalTrials.gov NCT00896480), patients received ≤24 doses of MAGE-A3 immunotherapeutic (4-cycle schedule). At screening, two skin lesions were biopsied for MAGE-A3 expression analysis and presence/absence of a previously identified gene signature (GS) associated with favourable clinical outcome. Clinical activity was assessed in terms of clinical response, time-to-treatment failure (TTF) and progression-free survival (PFS). Adverse events (AEs) and serious AEs (SAEs) were recorded. MAGE-A3-specific immune responses were assessed. Clinical activity and immunogenicity were analysed overall and separately in patients with 2/2 (GS+/+), 1/2 (GS+/-) or 0/2 (GS-/-) biopsies presenting GS.RESULTSOf 49 screened patients, 32 had MAGE-A3-positive tumours; 24 (8 GS+/+, 8 GS+/-, 8 GS-/-) were treated. Two complete (GS+/+ patients) and two partial responses (one GS+/+, one GS+/-) were reported; of note, one of the two complete responses was unlikely to be related to the study treatment. Median TTF and PFS were 14.8 and 7.2 months for GS+/+, 2.3 and 2.8 months for GS+/- and 2.4 and 2.9 months for GS-/- patients. Three grade 3 AEs and two SAEs unrelated to treatment were reported. All patients were seropositive for MAGE-A3 antibodies on vaccination with no differences between the different GS profiles. MAGE-A3-specific CD4+ and CD8+ T cell immunogenicity was detected; 12/16 (75.0%) of patients presented CD4+ T cell responses.CONCLUSIONTreatment with MAGE-A3 immunotherapeutic showed signs of clinical activity in GS+/+ patients. Treatment was well tolerated and immunogenic. No differences in immune responses according to GS status were observed.TRIAL REGISTRATION NUMBERNCT00896480 (Results).

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MAGE-A3 Positive Muscle Invasive Bladder Carcinoma

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