Mayra Shanley
A5061272107- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Systemic Lupus Erythematosus Research
- Lymphoma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Tuberculosis Research and Epidemiology
- Hematopoietic Stem Cell Transplantation
- Neuroinflammation and Neurodegeneration Mechanisms
- Virus-based gene therapy research
- Immune cells in cancer
- SARS-CoV-2 and COVID-19 Research
- Acute Myeloid Leukemia Research
- COVID-19 Clinical Research Studies
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Chronic Lymphocytic Leukemia Research
- Glioma Diagnosis and Treatment
- Herpesvirus Infections and Treatments
- RNA Interference and Gene Delivery
- Mesenchymal stem cell research
- Single-cell and spatial transcriptomics
- Platelet Disorders and Treatments
The University of Texas MD Anderson Cancer Center
2018-2025
Abstract There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 interleukin-15 (CAR19/IL-15) in 37 patients with CD19 + B malignancies. The primary objectives were safety efficacy, defined as day 30 overall response (OR). Secondary included 100 response, progression-free survival, survival CAR19/IL-15 NK persistence....
Glioblastoma multiforme (GBM), the most aggressive brain cancer, recurs because glioblastoma stem cells (GSCs) are resistant to all standard therapies. We showed that GSCs, but not normal astrocytes, sensitive lysis by healthy allogeneic natural killer (NK) in vitro. Mass cytometry and single-cell RNA sequencing of primary tumor samples revealed GBM tumor-infiltrating NK acquired an altered phenotype associated with impaired lytic function relative matched peripheral blood from patients or...
Natural killer (NK)-cell recognition and function against NK-resistant cancers remain substantial barriers to the broad application of NK-cell immunotherapy. Potential solutions include bispecific engagers that target activity via an NK-activating receptor when simultaneously targeting a tumor-specific antigen, as well enhancing functionality using IL12/15/18 cytokine pre-activation.
Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is promising, with early-phase clinical studies showing encouraging responses. However, the transcriptional signatures that control fate CAR-NK after infusion and factors influence tumor remain poorly understood. We performed single-cell RNA sequencing mass cytometry to study heterogeneity their in vivo evolution adoptive transfer, from phase relapse. Using a preclinical model noncurative lymphoma samples responder...
Glioblastoma (GBM) is an aggressive brain cancer with limited therapeutic options. Natural killer (NK) cells are innate immune strong anti-tumor activity and may offer a promising treatment strategy for GBM. We compared the anti-GBM of NK engineered to express interleukin (IL)-15 or IL-21. Using multiple in vivo models, IL-21 were superior IL-15 both terms safety long-term activity, locoregionally administered proving toxic ineffective at tumor control. displayed unique chromatin...
Multiple factors in the design of a chimeric antigen receptor (CAR) influence CAR T-cell activity, with costimulatory signals being key component. Yet, impact domains on downstream signaling and subsequent functionality CAR-engineered natural killer (NK) cells remains largely unexplored. Here, we evaluated various CAR-NK cell using CD70-targeting CAR. We found that CD28, molecule not inherently present mature NK cells, significantly enhanced antitumor efficacy long-term cytotoxicity both...
Myelodysplastic syndrome and acute myeloid leukemia (AML) belong to a continuous disease spectrum of malignancies with poor prognosis in the relapsed/refractory setting necessitating novel therapies. Natural killer (NK) cells from patients display global dysfunction impaired killing capacity, altered metabolism, an exhausted phenotype at single-cell transcriptomic proteomic levels. In this study, we identified that was mediated through cross-talk between NK blasts cell-cell contact. cell...
Natural killer (NK) cells are innate lymphocytes recognized for their important role against tumor cells. NK expressing chimeric antigen receptors (CARs) have enhanced effector function various type of cancer and attractive contenders the next generation immunotherapies. However, a number factors hindered application cellular therapy, including poor in vitro growth kinetics relatively low starting percentages within mononuclear cell fraction peripheral blood or cord (CB). To overcome these...
Cytomegalovirus (CMV) antigens occur in glioblastoma but not normal brains, making them desirable immunologic targets.Highly functional autologous polyclonal CMV pp65-specific T cells from patients with were numerically expanded under good manufacturing practice compliant conditions and administered after 3 weeks of lymphodepleting dose-dense temozolomide (100 mg/m2) treatment. The phase I component used a 3+3 design, ascending through four dose levels (5 × 106-1 108 cells). Treatment...
Adoptive cell therapy with virus-specific T cells has been used successfully to treat life-threatening viral infections, supporting application of this approach coronavirus disease 2019 (COVID-19). We expand severe acute respiratory syndrome 2 (SARS-CoV-2) from the peripheral blood COVID-19-recovered donors and non-exposed controls using different culture conditions. observe that choice cytokines modulates expansion, phenotype, hierarchy antigenic recognition by SARS-CoV-2 cells. Culture...
CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the of NK surveillance acute myeloid leukemia (AML). cells patients AML had lower expression CD226. CRISPR-Cas9 deletion led reduced LFA-1 recruitment, poor decreased anti-leukemic activity. Engineering express chimeric antigen receptor targeting CD38 (CAR38) could...
Abstract Adoptive cell therapies (ACT) leverage tumor-immune interactions to cure cancer. Despite promising phase I/II clinical trials of chimeric-antigen-receptor natural killer (CAR-NK) therapies, molecular mechanisms and cellular properties required achieve benefits in broad cancer spectra remain underexplored. While vitro vivo experiments are this endeavor, they typically expensive, laborious, limited targeted investigations. Here, we present ABMACT (Agent-Based Model for Cell Therapy),...
Abstract Chimeric antigen receptor (CAR) natural killer (NK) cell immunotherapy offers a promising approach against cancer. However, the molecular mechanisms governing CAR NK activity remain poorly understood. In this study, we identified transcription factor cAMP response element modulator (CREM) as pivotal regulator of function. Using Raji model, single-cell RNA sequencing revealed marked upregulation CREM in cells during peak anti-tumor after adoptive transfer. expression correlated with...
Background B cells play a pivotal role in regulating the immune response. The induction of cell-mediated immunosuppressive function requires cell activating signals. However, mechanisms by which activated mediate T-cell suppression are not fully understood. Methods We investigated potential contribution metabolic activity to performing vitro experiments and analyzing clinical samples using mass cytometry single-cell RNA sequencing. Results Here we show that following activation, acquire an...
Acute graft-vs.-host (GVHD) disease remains a common complication of allogeneic stem cell transplantation with very poor outcomes once the becomes steroid refractory. Mesenchymal cells (MSCs) represent promising therapeutic approach for treatment GVHD, but so far this strategy has had equivocal clinical efficacy. Therapies using MSCs require optimization taking advantage plasticity these in response to different microenvironments. In study, we aimed optimize cord blood tissue derived (CBti...
2515 Background: Cytomegalovirus (CMV) antigens are present in > 90% of GBMs but not normal brain making it an attractive immunological target. Methods: Highly functional autologous polyclonal CMV pp65 specific T cells were expanded under GMP-compliant conditions from GBM patients and administered after 3 weeks lymphodepleting dose-dense temozolomide (ddTMZ, 100 mg/m 2 ). The phase I component used a 3+3 design ascending through four dose levels (5 x 10 6 to 1 8 cells). Treatment was...
SUMMARY Adoptive cell therapy with viral-specific T cells has been successfully used to treat life-threatening viral infections, supporting the application of this approach against COVID-19. We expanded SARS-CoV-2 T-cells from peripheral blood COVID-19-recovered donors and non-exposed controls using different culture conditions. observed that choice cytokines modulates expansion, phenotype hierarchy antigenic recognition by T-cells. Culture IL-2/4/7 but not other cytokine-driven conditions...