Meenakshi Hegde
A5032050779- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Nanowire Synthesis and Applications
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Cell Function and Interaction
- Glioma Diagnosis and Treatment
- Advancements in Semiconductor Devices and Circuit Design
- Single-cell and spatial transcriptomics
- Cytomegalovirus and herpesvirus research
- Silicon Carbide Semiconductor Technologies
- Immunodeficiency and Autoimmune Disorders
- Neuroblastoma Research and Treatments
- Hematopoietic Stem Cell Transplantation
- Blood disorders and treatments
- Advanced Electron Microscopy Techniques and Applications
- Cancer Immunotherapy and Biomarkers
- Platelet Disorders and Treatments
- Cancer Research and Treatments
- Nanofabrication and Lithography Techniques
- Acute Lymphoblastic Leukemia research
- Cancer Cells and Metastasis
- T-cell and B-cell Immunology
- Biosimilars and Bioanalytical Methods
Texas Children's Hospital
2015-2025
Baylor College of Medicine
2016-2025
Houston Methodist
2014-2025
Methodist Hospital
2014-2025
Children's Cancer Center
2012-2025
Dan L Duncan Comprehensive Cancer Center
2024
Georg Speyer Haus
2016
National Cancer Institute
2016
University of Florida
2016
Methodist Hospital
2013
Purpose The outcome for patients with metastatic or recurrent sarcoma remains poor. Adoptive therapy tumor-directed T cells is an attractive therapeutic option but has never been evaluated in sarcoma. Patients and Methods We conducted a phase I/II clinical study which recurrent/refractory human epidermal growth factor receptor 2 (HER2) –positive received escalating doses (1 × 10 4 /m to 1 8 ) of expressing HER2-specific chimeric antigen CD28.ζ signaling domain (HER2-CAR cells). Results...
<h3>Importance</h3> Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. <h3>Objective</h3> To determine whether systemic administration of HER2-specific chimeric antigen receptor (CAR)–modified virus-specific T cells (VSTs) safe these have antiglioblastoma activity. <h3>Design, Setting, Participants</h3> In this open-label phase 1 dose-escalation study conducted at Baylor College Medicine, Houston Methodist Hospital, Texas Children’s with progressive...
In preclinical models of glioblastoma, antigen escape variants can lead to tumor recurrence after treatment with CAR T cells that are redirected single antigens. Given the heterogeneous expression antigens on glioblastomas, we hypothesized a bispecific molecule would mitigate and improve antitumor activity cells. Here, created joins HER2-binding scFv an IL13Rα2-binding IL-13 mutein make tandem exodomain (TanCAR) CD28.ζ endodomain. We determined patient TanCAR showed distinct binding HER2 or...
Targeted T cells are emerging as effective non-toxic therapies for cancer. Multiple elements, however, contribute to the overall pathogenesis of cancer through both distinct and redundant mechanisms. Hence, targeting multiple cancer-specific markers simultaneously could result in better therapeutic efficacy. We created a functional chimeric antigen receptor-the TanCAR, novel artificial molecule that mediates bispecific activation cells. demonstrate feasibility cumulative integration...
Glioblastoma (GBM) is the most common primary malignant brain cancer, and currently incurable. Chimeric antigen receptor (CAR) T cells have shown promise in GBM treatment. While we that combinatorial targeting of 2 glioma antigens offsets escape enhances T-cell effector functions, interpatient variability surface expression between patients hinders clinical impact pairs. This study addresses 3 using a single CAR product for broader application.
Preclinical and early clinical studies have demonstrated that chimeric antigen receptor (CAR)-redirected T cells are highly promising in cancer therapy. We observed targeting HER2 a glioblastoma (GBM) cell line results the emergence of HER2-null tumor maintain expression nontargeted tumor-associated antigens. Combinational these antigens could therefore offset this escape mechanism. studied single-cell coexpression patterns HER2, IL-13Rα2, EphA2 primary GBM samples using multicolor flow...
Abstract Chimeric antigen receptor (CAR) T-cells targeting CD19 demonstrate remarkable efficacy in treating B-lineage acute lymphoblastic leukemia (BL-ALL), yet up to 39% of treated patients relapse with CD19(−) disease. We report that escape is associated downregulation, but preservation, targetable expression CD20 and CD22. Accordingly, we reasoned broadening the spectrum CD19CAR include both CD22 would enable them target BL-ALL while preserving their upfront efficacy. created a...
Abstract Triple-negative breast cancer (TNBC) is an aggressive disease lacking targeted therapy. In this study, we developed a CAR T cell–based immunotherapeutic strategy to target TEM8, marker initially defined on endothelial cells in colon tumors that was discovered recently be upregulated TNBC. were upon specific recognition of TEM8 secreted immunostimulatory cytokines and killed tumor as well TEM8-positive TNBC cells. Notably, the stem–like cells, offsetting formation mammospheres...
Abstract Refractory metastatic rhabdomyosarcoma is largely incurable. Here we analyze the response of a child with refractory bone marrow to autologous HER2 CAR T cells. Three cycles cells given after lymphodepleting chemotherapy induces remission which consolidated four more T-cell infusions without lymphodepletion. Longitudinal immune-monitoring reveals remodeling receptor repertoire immunodominant clones and serum autoantibodies reactive oncogenic signaling pathway proteins. The disease...
Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART. We reasoned that molecular dynamics at the CART immune synapse (CARIS) could explain differences in their rejection kinetics. observed CD28.ζ-CART engaged brief highly lethal CARIS and mastered serial killing, whereas 4-1BB.ζ-CART formed lengthy relied on robust expansion cooperative killing. analyzed...
Subsequent malignancies are well-documented complications in long-term follow-up of cancer patients. Recently, genetically modified immune effector (IE) cells have shown benefit hematologic and being evaluated clinical trials for solid tumors. Although the short-term IE well described, there is limited literature summarizing follow-up, including subsequent malignancies. We retrospectively reviewed data from 340 patients treated across 27 investigator-initiated pediatric adult at our center....
Glioblastoma (GBM) is the most common primary brain cancer in adults and virtually incurable. Recent studies have shown that cytomegalovirus (CMV) present majority of GBMs. To evaluate whether CMV antigens pp65 IE1, which are expressed GBMs, could be targeted by CMV-specific T cells, we measured frequency cells targeting IE1 peripheral blood a cohort 11 sequentially diagnosed CMV-seropositive GBM patients, evaluated it was feasible to expand autologous for future clinical studies. All...
Meeting abstracts Glioblastoma (GBM) remains incurable with current standard-of-care therapies. Adoptive T cell transfer holds the promise to improve outcomes for GBM patients. We report on results of Phase I clinical study, [NCT01109095][1], administering autologous CMV.pp65 cells
ABSTRACT Background Immune effector cell (IEC) therapies, including chimeric antigen receptor (CAR)‐modified T‐cell therapy, have shown efficacy in pediatric B‐cell acute lymphoblastic leukemia (B‐ALL) and are being investigated for other malignancies. A common toxicity associated with IEC therapy is cytokine release syndrome (CRS), which can lead to cardiovascular decompensation due systemic inflammation. Data limited regarding adverse effects children. This study aims describe the effect...
Abstract The efficacy of CAR T-cells (CART) in solid tumors is limited by immune inhibition. In our study, we observed that effector cytokines mediated the upregulation PD-L1 immune-checkpoint primary glioblastoma (GBM). To offset inhibitory signal, engineered PD-1 checkpoint reversal receptors (CPR) with a CD28 or 41BB co-stimulatory endodomain and co-expressed them first-generation CD28-containing second-generation HER2-specific (CPR/CART) using bicistronic vectors. We found bipartite...
<p>Analysis of CAR immune synapse (CARIS) with HER2+ GBM cells.</p>
<p>Immunophenotype and immune-checkpoint receptor expression in patient-derived CPR/CART cells.</p>
<p>Expression of CAR/CPR on T cells and HER2/PD-L1 tumor cells.</p>
<p>Summary of CPR/CART design and characterization CARζ co-expressing CPR containing CD28 or 4-1BB signaling.</p>