A5053828591- Ocular Oncology and Treatments
- Immunotherapy and Immune Responses
- Retinal Development and Disorders
- Cancer Immunotherapy and Biomarkers
- Nanoplatforms for cancer theranostics
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Cutaneous Melanoma Detection and Management
- Colorectal Cancer Treatments and Studies
- Multiple Myeloma Research and Treatments
- Cancer-related Molecular Pathways
- Adversarial Robustness in Machine Learning
- Cancer Research and Treatments
- Cancer Mechanisms and Therapy
- Melanoma and MAPK Pathways
- Anomaly Detection Techniques and Applications
- Autonomous Vehicle Technology and Safety
- Hepatocellular Carcinoma Treatment and Prognosis
- Advanced Fluorescence Microscopy Techniques
- Protein Degradation and Inhibitors
- melanin and skin pigmentation
- Cell Adhesion Molecules Research
- Mechanisms of cancer metastasis
Sidney Kimmel Cancer Center
2016-2025
Thomas Jefferson University
2016-2025
Sidney Kimmel Comprehensive Cancer Center
2025
Keio University
2023-2025
Thomas Jefferson University Hospital
2011-2024
University of California, Irvine
2021-2024
Jefferson College
1997-2024
Jefferson University Hospitals
2022-2024
Tohoku University Hospital
2021-2024
Wills Eye Hospital
2009-2022
Uveal melanoma is characterized by mutations in GNAQ and GNA11, resulting mitogen-activated protein kinase pathway activation.To assess the efficacy of selumetinib, a selective, non-adenosine triphosphate competitive inhibitor MEK1 MEK2, uveal melanoma.Randomized, open-label, phase 2 clinical trial comparing selumetinib vs chemotherapy conducted from August 2010 through December 2013 among 120 patients with metastatic at 15 academic oncology centers United States Canada.One hundred one were...
Abstract In patients with previously treated metastatic uveal melanoma, the historical 1 year overall survival rate is 37% a median of 7.8 months. We conducted multicenter, single-arm, open-label phase 2 study tebentafusp, soluble T cell receptor bispecific (gp100×CD3), in 127 treatment-refractory melanoma (NCT02570308). The primary endpoint was estimation objective response based on RECIST (Response Evaluation Criteria Solid Tumours) v1.1. Secondary objectives included safety, survival,...
The mechanism by which malignant melanoma (MM) cells survive in lymph nodes is poorly understood. One possible MM can escape immune surveillance through upregulation of immunomodulatory enzymes such as indoleamine 2,3-dioxygenase (IDO). In this study, 25 cases node metastases from patients with long and short survival were evaluated for expression IDO the number Forkhead box p3 (FOXP3)-expressing regulatory T cells. Moderate to strong cytoplasmic was present all (15/15) poor survival. Eight...
Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification this heterogeneous cancer, several targeted immune therapies were approved increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) live tissue samples from 384 patients representing the full spectrum clinical, therapeutic, mutational, heterogeneity melanoma. PDX been...
Radioembolization as Salvage Therapy for Hepatic Metastasis of Uveal Melanoma: A Single-Institution ExperienceCarin F. Gonsalves1, David J. Eschelman1, Kevin L. Sullivan2, P. Rani Anne3, Laura Doyle3 and Takami Sato4Audio Available | Share
Abstract Uveal melanoma is the most common intraocular tumor in adults and often metastasizes to liver, leaving patients with few options. Recurrent activating mutations G proteins, Gαq Gα11, are observed approximately 93% of all uveal melanomas. Although therapeutic intervention downstream Gαq/11 targets has been unsuccessful treating melanoma, we have found that inhibitor, FR900359 (FR), effectively inhibits oncogenic signaling cells expressing either mutant or Gα11. Inhibition by FR...
PURPOSE This phase I study aimed to define the recommended II dose (RP2D) of tebentafusp, a first-in-class T-cell receptor/anti-CD3 bispecific protein, using three-week step-up dosing regimen, and assess its safety, pharmacokinetics, pharmacodynamics, preliminary clinical activity in patients with metastatic uveal melanoma (mUM). METHODS In this open-label, international, I/II study, HLA-A*02 or HLA-A*02:01+ mUM received tebentafusp 20 μg once week 1 30 2. Dose escalation (starting at 54 μg)...
Uveal melanoma is the most common eye cancer in adults. Approximately 50% of patients with uveal develop metastatic (mUM) liver, even after successful treatment primary lesions. mUM refractory to current chemo- and immune-therapies, die within a year. characterized by gain-of-function mutations
We have previously reported a clinical trial of human cancer vaccine consisting autologous tumor cells modified with the hapten, dinitrophenyl (DNP), in patients stage III melanoma. Here we present follow-up report expanded to 214 5-year follow-up.Two hundred fourteen melanoma (117 IIIC and 97 IIIB) who were melanoma-free after standard lymphadenectomy treated multiple intradermal injections autologous, DNP-modified mixed bacille Calmette-Guérin. Four dosage schedules tested sequentially,...
PURPOSE To determine whether treatment with an autologous whole-cell vaccine modified the hapten dinitrophenyl (DNP vaccine) is effective postsurgical adjuvant for melanoma patients clinically evident nodal metastases. PATIENTS AND METHODS Eligible had regional metastases that were large enough (> or = 3 cm diameter) to prepare vaccine. Following standard lymphadenectomy, treated DNP on a monthly weekly schedule. RESULTS Of 62 metastasis in single lymph node bed (stage III), 36 are alive...
Uveal melanoma is the most common primary intraocular malignancy in adults and liver site for systemic metastases. We conducted a phase II clinical trial patients with hepatic metastases from uveal using chemoembolization of artery 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) dissolved ethiodized oil. Gelatin sponge particles were used as transiently occlusive agent. The responses metastases, overall survival, time to progression side-effects related evaluated. Thirty enrolled. Twenty-four...
The prognosis of patients with metastatic uveal melanoma is poor and there are limited therapeutic options. C-kit expressed in the majority melanoma. In this pilot trial, we examined toxicity efficacy sunitinib malate, a multitarget tyrosine kinase inhibitor, Twenty expressing c-kit, 17 whom failed previous treatments, were included study. Patients received malate 37.5 mg daily continuously 4-week cycles. evaluation response was carried out every 8 weeks. overall survival (OS)...
Aim: To compare PD-L1 expression between metastatic uveal melanoma (MUM) and cutaneous (MCM). Materials & methods: A total of 295 MCM 78 MUM specimens were analyzed for tumor cell expression. Additionally, 91 45 PD-1 on tumor-infiltrating lymphocytes. Results: 77/295 (26.1%) expressed as compared to 4/78 (5.1%) (p < 0.0001). lymphocytes was greater in (73.6%; 67/91) than (51.1%; 23/45), respectively = 0.009). Conclusion: Significant differences exist MUM. The lower may provide a rationale...
TRX518 is a mAb engaging the glucocorticoid-induced TNF receptor-related protein (GITR). This open-label, phase I study (TRX518-003) evaluated safety and efficacy of repeated dose monotherapy in combination with gemcitabine, pembrolizumab, or nivolumab advanced solid tumors.
Background Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising in previously treated mUM 1-year OS of 62% the primary analysis study IMCgp100-102. Here we report long-term from this phase 1/2 pretreated mUM. Patients methods received tebentafusp weekly intravenous at 20 µg dose 1, 30 2 either 54, 64, 68, or 73 (phase 1) 68 2) 3+. The objective...
The objective of this study was to evaluate the usefulness resection metastatic uveal melanoma and analyze characteristics patients who may benefit from surgical intervention. PATIENTS AND METHODS Twelve underwent removal metastasis between 1976 1998. Data regarding primary melanoma, systemic metastasis, procedures, outcomes were reviewed retrospectively.There seven with liver metastases, two lung one brain metastases in other organs. Median time 8 years. Seven 12 asymptomatic when they...