A5027869313- Prostate Cancer Treatment and Research
- Hormonal and reproductive studies
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- PARP inhibition in cancer therapy
- Cell Adhesion Molecules Research
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Cancer Cells and Metastasis
- Ocular Infections and Treatments
- Cancer Research and Treatments
- Glycosylation and Glycoproteins Research
- Chemokine receptors and signaling
- Mass Spectrometry Techniques and Applications
- Biosimilars and Bioanalytical Methods
- HER2/EGFR in Cancer Research
- Cancer-related Molecular Pathways
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Lymphoma Diagnosis and Treatment
- Psoriasis: Treatment and Pathogenesis
- Immune cells in cancer
University of Virginia
2016-2025
University of Delhi
2024
University of Virginia Cancer Center
2016-2024
KIIT University
2024
Govind Ballabh Pant Hospital
2018-2022
AbbVie (United States)
2016-2022
Novartis Foundation
2022
National Institute of Technology Hamirpur
2017-2020
Institute of Post Graduate Medical Education and Research
2018
Roger Williams Medical Center
2018
Abstract Purpose: Elevated cyclin D1 in human pancreatic cancer correlates with poor prognosis. Because is invariably resistant to chemotherapy, the goal of this study was examine whether drug resistance cells part attributed overexpression. Experimental Design: Stable overexpression and small interfering RNA (siRNA)–mediated knockdown were done newly established Ela-myc tumor cell line. Cisplatin sensitivity control, overexpressing, siRNA-transfected determined by...
Abstract Purpose: This study reports a phase I immunotherapy trial in 23 women with metastatic breast cancer consisting of eight infusions anti-CD3 × anti-HER2 bispecific antibody (HER2Bi) armed anti-CD3–activated T cells (ATC) combination low-dose IL-2 and granulocyte-macrophage colony-stimulating factor to determine safety, maximum tolerated dose (MTD), technical feasibility, T-cell trafficking, immune responses, time progression, overall survival (OS). Experimental Design: ATC were...
Abstract Costimulatory receptors such as glucocorticoid-induced tumor necrosis factor receptor–related protein (GITR) play key roles in regulating the effector functions of T cells. In human clinical trials, however, GITR agonist antibodies have shown limited therapeutic effect, which may be due to suboptimal receptor clustering-mediated signaling. To overcome this potential limitation, a rational engineering approach is needed optimize agonist-based immunotherapies. Here we show bispecific...
Background The survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment anti-GD2 monoclonal antibodies prompted our investigation into the safety potential clinical benefits of anti-CD3×anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs). Preclinical studies demonstrated high cytotoxicity GD2BATs against GD2+cell lines, leading to initiation a phase I/II study recurrent/refractory patients. Methods 3+3 dose escalation I (...
Abstract Integrin β4 (ITGB4) has been shown to play an important role in the regulation of cancer stem cells (CSC). Immune targeting ITGB4 represents a novel approach target this cell population, with potential clinical benefit. We developed two immunologic strategies ITGB4: protein–pulsed dendritic (ITGB4-DC) for vaccination and adoptive transfer anti-CD3/anti-ITGB4 bispecific antibody (ITGB4 BiAb)–armed tumor-draining lymph node T cells. Two immunocompetent mouse models were utilized...
Abstract The consequence of activation status or gain/loss an X-chromosome in terms the expression tumor suppressor genes oncogenes breast cancer has not been clearly addressed. In this study, we investigated X-chromosomes a panel human cell lines, carcinoma, and adjacent mammary tissues murine epithelial sublines ranging from low to high invasive potentials. Results show that most lines were homozygous, but both benign heterozygous for highly polymorphic X-loci (IDS G6PD). On other hand,...
Abstract Background The ganglioside GD2 is an attractive target for immunotherapy of neuroectodermal tumors. We tested a unique bispecific antibody anti‐CD3 × anti‐GD2 (3F8BiAb) its ability to redirect activated T cells (ATC) GD2‐positive neuroblastomas. Procedure ATC were generated from normal human peripheral blood mononuclear (PBMC) by stimulating the PBMC with OKT3 and expanding in presence interleukin 2 (IL‐2) 14 days. armed 3F8BiAb (100 ng/10 6 cells) or Her2BiAb (50 prior use. 3F8...
Background . New nontoxic targeted approaches are needed for patients with castrate resistant prostate cancer (CRPC). Our preclinical studies show that activated T cells (ATC) armed anti-CD3 x anti-Her2 bispecific antibody (Her2Bi) kill lines, induce a Th 1 cytokine pattern upon engagement of tumor cells, prevent the development tumors, and retard growth in immunodeficient mice. These provided strong rationale our phase I dose-escalation pilot study to test ATC Her2Bi (aATC) safety men CRPC....
Purpose This was a phase I/II adoptive T cell trial in 7 locally advanced and metastatic pancreatic cancer patients using 3-8 infusions of anti-CD3 x anti-EGFR bispecific antibody armed activated cells (BATs) to determine safety, the maximum tolerated dose (MTD), immune responses, time progression (TTP), overall survival (OS).
Abstract Purpose The purpose of this study was to determine the safety, feasibility, and immunologic responses treating grade 4 astrocytomas with multiple infusions anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination radiation chemotherapy. Methods This phase I used a 3 + dose escalation design test safety feasibility intravenously infused EGFR BATs temozolomide (TMZ) patients newly diagnosed (AG4). After finding feasible dose, an expansion cohort...
Abstract Purpose: We have previously shown that p90 ribosomal protein S6 kinase 4 (RSK4), an X-linked gene, is highly up-regulated in mammary tumors of MMTV-c-Myc transgenic mice. In this study, we further investigated whether RSK4 inhibits or promotes breast tumor growth and progression. Experimental Design: Stable overexpression small interfering RNA–mediated knockdown was done the MDA-MB-231 cell line. clones were tested for proliferation, anchorage-independent soft agar, invasive...
Cryotherapy offers a minimally invasive treatment option for the management of both irresectable and localized prostate, liver, pulmonary, renal tumors. The antineoplastic effects cryotherapy are mediated by direct tumor lysis indirect effects, such as intracellular dehydration, pH changes, microvascular damage resulting in ischemic necrosis. In this study, we investigated whether percutaneous cryoablation lung metastasis from cell carcinoma (RCC) combination with aerosolized...
Abstract CD137 (TNFRSF9, 4-1BB) agonist antibodies (mAb) have demonstrated potent antitumor activity with memory response while causing hepatotoxicity in mouse models. In clinical trials, the degrees of liver toxicity anti-CD137 vary from grade 4 transaminitis (urelumab) to nonexistent (utomilumab). To exploit potential signaling, we identified a new class mAbs strong potency without significant vivo compared agonists previously reported. These are cross-reactive and cynomolgus monkey showed...
Abstract Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and available for treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In this single-arm, two-cohort, multicenter clinical study, potential racial differences in immune responses to sipuleucel-T mCRPC were explored. Patients’ blood samples obtained assess serum cytokines, humoral responses, immunity markers before after...
Radiation Therapy (RT) can modulate the immune system and generate anti-tumor T cells. However, this anti-tumor-activity is countered by radiation-induced immunosuppression (RIIS). Clinical advantages of proactively sparing RT dose to rich organs have not previously been evaluated. We conducted a phase II randomized trial from 2020 2023, enrolling 51 early-stage lung cancer patients treated with SBRT, evaluate effect reduction on RIIS. Two groups were: RIIS-optimized-treatment (lowering...
ABSTRACT Tumor clearance by T cells is impaired insufficient tumor antigen recognition, infiltration, and the immunosuppressive microenvironment (TME). Although targeted cell therapy circumvents failures in suppression TME failure to infiltrate can hinder these cells. Checkpoint inhibitors (CPI) promises reverse be combined with bispecific antibody armed (BATs) improve clinical outcomes. CPIs require target pathway of inhibition active elicit a therapeutic response. We hypothesize that...