Megan M. Davis
A5044053032- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Biosimilars and Bioanalytical Methods
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Biomedical Ethics and Regulation
- Cancer Cells and Metastasis
- Multiple Myeloma Research and Treatments
- Chronic Lymphocytic Leukemia Research
- Nanowire Synthesis and Applications
- Monoclonal and Polyclonal Antibodies Research
- Semiconductor materials and devices
- Cytomegalovirus and herpesvirus research
- Single-cell and spatial transcriptomics
- Silicon Carbide Semiconductor Technologies
- RNA and protein synthesis mechanisms
- Endometrial and Cervical Cancer Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Mechanical Circulatory Support Devices
- Prostate Cancer Treatment and Research
- Ovarian cancer diagnosis and treatment
University of Pennsylvania
2016-2025
Torbay and South Devon NHS Foundation Trust
2020
Emory University Hospital
2019
Medical University of South Carolina
2016
CRISPR-Cas9 gene editing provides a powerful tool to enhance the natural ability of human T cells fight cancer. We report first-in-human phase 1 clinical trial test safety and feasibility multiplex engineer in three patients with refractory Two genes encoding endogenous cell receptor (TCR) chains, TCRα (
BACKGROUND. CAR T cells are a promising therapy for hematologic malignancies. B cell maturation antigen (BCMA) is rational target in multiple myeloma (MM).
Chimeric antigen receptors (CAR) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR cells ineffective for solid tumors date. We found the cell-surface molecule c-Met was expressed ∼50% breast tumors, prompting construction a cell specific c-Met, which halted tumor growth immune-incompetent mice with xenografts. then evaluated safety and feasibility treating metastatic cancer intratumoral administration...
The success of chimeric antigen receptor (CAR)-mediated immunotherapy in acute lymphoblastic leukemia (ALL) highlights the potential T-cell therapies with directed cytotoxicity against specific tumor antigens. efficacy CAR therapy depends on engraftment and persistence T cells following adoptive transfer. Most protocols for engineering routinely expand
BACKGROUND. Multiple myeloma is usually fatal due to serial relapses that become progressively refractory therapy. CD19 typically absent on the dominant multiple cell population but may be present minor subsets with unique myeloma-propagating properties. To target cells, we clinically evaluated autologous T cells transduced a chimeric antigen receptor (CAR) against (CTL019).
Key points T cells from patients early in myeloma therapy exhibit better fitness for CAR manufacturing than those relapsed/refractory patients. may be more effective if manufactured before onset of disease.
In chronic lymphocytic leukemia (CLL) patients who achieve a complete remission (CR) to anti-CD19 chimeric antigen receptor T cells (CART-19), remissions are remarkably durable. Preclinical data suggesting synergy between CART-19 and the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib prompted us conduct prospective single-center phase 2 trial in which we added autologous humanized binding domain (huCART-19) with CLL not CR despite ≥6 months of ibrutinib. The primary endpoints were...
Chimeric antigen receptor (CAR) T cell therapy targeting CD19 has achieved tremendous success treating B malignancies; however, some patients fail to respond due poor autologous fitness. To improve response rates, we investigated whether disruption of the co-inhibitory receptors CTLA4 or PD-1 could restore CART function. CRISPR-Cas9-mediated deletion in preclinical models leukemia and myeloma improved CAR proliferation anti-tumor efficacy. Importantly, this effect was specific not seen upon...
Chimeric antigen receptor (CAR) T cells have not induced meaningful clinical responses in solid tumors. Loss of cell stemness, poor expansion capacity, and exhaustion during prolonged tumor exposure are major causes CAR therapeutic resistance. Single-cell RNA-sequencing analysis from a first-in-human trial metastatic prostate cancer identified two independently validated states associated with antitumor potency or lack efficacy. Low expression PRDM1 , encoding the BLIMP1 transcription...
Chimeric antigen receptor (CAR) T cells have induced remarkable antitumor responses in B cell malignancies. Some patients do not respond because of deficiencies that hamper the expansion, persistence, and effector function these cells. We used longitudinal immune profiling to identify phenotypic pharmacodynamic changes CD19-directed CAR with chronic lymphocytic leukemia (CLL). expression maintenance was also investigated this can affect response durability. failure accompanied by preexisting...
Chimeric antigen receptor (CAR) T cells demonstrate remarkable success in treating hematological malignancies, but their effectiveness non-hematopoietic cancers remains limited. This study proposes enhancing CAR cell function and localization solid tumors by modifying the epigenome governing tissue-residency adaptation early memory differentiation. We identify that a key factor human tissue-resident (CAR-T
Genome engineering methods have advanced greatly with the development of programmable nucleases, but for quantifying on- and off-target cleavage sites associated deletions remain nascent. Here, we report an improvement GUIDE-seq method, iGUIDE, which allows filtering mispriming events to clarify true signal. Using specify locations Cas9-guided four guide RNAs, characterize deletions, show that naturally occurring background DNA double-strand breaks are open chromatin, gene dense regions,...
The advent of engineered T cells as a form immunotherapy marks the beginning new era in medicine, providing transformative way to combat complex diseases such cancer. Following FDA approval CAR directed against CD19 protein for treatment acute lymphoblastic leukemia and diffuse large B cell lymphoma, are poised enter mainstream oncology. Despite this success, number patients unable receive therapy due inadequate numbers or rapid disease progression. Furthermore, lack response is some cases...
Abstract Chimeric antigen receptor (CAR) T-cells directed against CD19 have drastically altered outcomes for children with relapsed and refractory acute lymphoblastic leukemia (r/r ALL). Pediatric patients r/r ALL treated CAR-T are at increased risk of both cytokine release syndrome (CRS) sepsis. We sought to investigate the biologic differences between CRS sepsis develop predictive models which could accurately differentiate from time critical illness. identified 23 different cytokines that...
7004 Background: A substantial proportion of patients (pts) with relapsed/refractory (R/R) non-Hodgkin lymphomas (NHL) will not derive a long-term benefit from the existing anti-CD19 chimeric antigen receptor (CAR) T cells. To enhance therapeutic efficacy, we have engineered huCART19-IL18, 4 th generation 4-1BB construct, armored ability to secrete pro-inflammatory cytokine, IL-18. Methods: This is first-in-human trial using huCART19-IL18 for CD19+ B-cell malignancies (NCT04684563)....