Dean A. Lee
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View article: CXCL10-induced chemotaxis of ex vivo-expanded natural killer cells combined with NKTR-255 enhances anti-tumor efficacy in osteosarcoma
CXCL10-induced chemotaxis of ex vivo-expanded natural killer cells combined with NKTR-255 enhances anti-tumor efficacy in osteosarcoma Open
Osteosarcoma (OSA) has a dismal prognosis despite surgical resection and multiagent chemotherapy. While adoptive natural killer (NK) cell therapies have been successful in hematological malignancies, the application in solid tumors is chal…
View article: Allogeneic Polyclonal CD38KO/CD38-CAR γδT Cells For The Treatment Of T Cell Malignancies
Allogeneic Polyclonal CD38KO/CD38-CAR γδT Cells For The Treatment Of T Cell Malignancies Open
Relapsed and refractory T cell malignancies are associated with poor clinical outcomes. Although autologous CAR-αβT cells have been employed in the treatment of several cancers, generating CAR-T cells for T cell malignancies remains challe…
View article: Harmonized immune recovery monitoring after HCT: evidence and practical guidance from the Westhafen Intercontinental Group
Harmonized immune recovery monitoring after HCT: evidence and practical guidance from the Westhafen Intercontinental Group Open
Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative option for patients with high-risk malignancies and nonmalignant disorders. Long-term survival depends on robust immune reconstitution (IR), which governs overall immun…
View article: Natural killer cells in skin: a unique opportunity to better characterize the many facets of an overlooked secondary lymphoid organ
Natural killer cells in skin: a unique opportunity to better characterize the many facets of an overlooked secondary lymphoid organ Open
Natural killer (NK) cells are lymphoid-derived cells that play a critical role in bridging innate and adaptive immunity. Given their ability to recognize and directly kill targets possessing missing or altered self-proteins and to induce i…
View article: Juvenile myelomonocytic leukemia stem cells are sensitive to NK cell–mediated lysis and express targetable antigens
Juvenile myelomonocytic leukemia stem cells are sensitive to NK cell–mediated lysis and express targetable antigens Open
Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm for which hematopoietic stem cell transplantation is the only curative treatment. Innovative therapies are needed to address high rates of morbidity, treatment-relate…
View article: Dark NKnight rising: a current perspective on NK cell and CAR-NK cell therapy
Dark NKnight rising: a current perspective on NK cell and CAR-NK cell therapy Open
Natural killer (NK) cell therapy began decades ago with administration of small doses of minimally-characterized cells known as cytokine-induced or lymphokine-activated killer cells (CIK or LAK, respectively). Methods and conditions that e…
View article: High-throughput drug screening identifies SMAC mimetics as enhancers of NK-cell cytotoxicity in chronic myeloid leukemia
High-throughput drug screening identifies SMAC mimetics as enhancers of NK-cell cytotoxicity in chronic myeloid leukemia Open
Natural killer (NK) cells have proven to be safe and effective immunotherapies, associated with favorable treatment responses in chronic myeloid leukemia (CML). Augmenting NK-cell function with oncological drugs could improve NK-cell–based…
View article: A framework integrating multiscale in-silico modeling and experimental data predicts CD33CAR-NK cytotoxicity across target cell types
A framework integrating multiscale in-silico modeling and experimental data predicts CD33CAR-NK cytotoxicity across target cell types Open
Uncovering mechanisms and predicting tumor cell responses to CAR-NK cytotoxicity is essential for improving therapeutic efficacy. Currently, the complexity of these effector-target interactions and the donor-to-donor variations in NK cell …
View article: Combinatorial immunotherapy with anti-ROR1 CAR NK cells and an IL-21 secreting oncolytic virus against neuroblastoma
Combinatorial immunotherapy with anti-ROR1 CAR NK cells and an IL-21 secreting oncolytic virus against neuroblastoma Open
Children with recurrent/metastatic neuroblastoma (NB) have a dismal survival (<25%). Novel therapies are desperately needed. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is highly expressed on NB. C021 is a selective oncolytic he…
View article: Comprehensive Drug Profiling and CRISPR Screening Reveal Essential Pathways for NK Cell Cytotoxicity
Comprehensive Drug Profiling and CRISPR Screening Reveal Essential Pathways for NK Cell Cytotoxicity Open
NK cell therapies offer great promise in treating hematological cancers due to their “off-the-shelf” applicability and reduced toxicity. However, challenges in specificity, potency, and longevity persist compared to T cell therapies. Genet…
View article: Trabectedin promotes oncolytic virus antitumor efficacy, viral gene expression, and immune effector function in models of bone sarcoma
Trabectedin promotes oncolytic virus antitumor efficacy, viral gene expression, and immune effector function in models of bone sarcoma Open
We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucid…
View article: Circumventing resistance within the Ewing sarcoma microenvironment by combinatorial innate immunotherapy
Circumventing resistance within the Ewing sarcoma microenvironment by combinatorial innate immunotherapy Open
Background Pediatric patients with recurrent/metastatic Ewing sarcoma (ES) have a dismal 5-year survival. Novel therapeutic approaches are desperately needed. Natural killer (NK) cell number and function are low in ES patient tumors, in la…
View article: CD38-CAR human NK cells in combination with ATRA enhance cytotoxicity against CD38-expressing hematologic malignancies
CD38-CAR human NK cells in combination with ATRA enhance cytotoxicity against CD38-expressing hematologic malignancies Open
CD38 is a metabolically active enzyme broadly expressed on the surface of normal and malignant hematologic cells. It has been targeted clinically with anti-CD38 monoclonal antibodies (mAbs), for which efficacy may be limited by natural kil…
View article: Efficiently targeting neuroblastoma with the combination of anti-ROR1 CAR NK cells and N-803 in vitro and in vivo in NB xenografts
Efficiently targeting neuroblastoma with the combination of anti-ROR1 CAR NK cells and N-803 in vitro and in vivo in NB xenografts Open
The prognosis for children with recurrent and/or refractory neuroblastoma (NB) is dismal. The receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is highly expressed on the surface of NB cells, provides a potential target for nov…
View article: A Careful Examination of Large Language Model Performance on Grade School Arithmetic
A Careful Examination of Large Language Model Performance on Grade School Arithmetic Open
Large language models (LLMs) have achieved impressive success on many benchmarks for mathematical reasoning. However, there is growing concern that some of this performance actually reflects dataset contamination, where data closely resemb…
View article: Results of a phase I trial with Haploidentical <scp>mbIL</scp>‐21 ex vivo expanded <scp>NK</scp> cells for patients with multiply relapsed and refractory <scp>AML</scp>
Results of a phase I trial with Haploidentical <span>mbIL</span>‐21 ex vivo expanded <span>NK</span> cells for patients with multiply relapsed and refractory <span>AML</span> Open
Natural killer (NK)‐cells have potent anti‐tumor effects, yet it remains unclear if they are effective for patients with relapsed acute myeloid leukemia (AML). In a phase I clinical trial, we treated 12 patients (median age 60 years) with …
View article: Trabectedin Enhances Oncolytic Virotherapy by Reducing Barriers to Virus Spread and Cytotoxic Immunity in Preclinical Pediatric Bone Sarcoma
Trabectedin Enhances Oncolytic Virotherapy by Reducing Barriers to Virus Spread and Cytotoxic Immunity in Preclinical Pediatric Bone Sarcoma Open
We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucid…
View article: Single-cell functional genomics reveals determinants of sensitivity and resistance to natural killer cells in blood cancers
Single-cell functional genomics reveals determinants of sensitivity and resistance to natural killer cells in blood cancers Open
Cancer cells can evade natural killer (NK) cell activity, thereby limiting anti-tumor immunity. To reveal genetic determinants of susceptibility to NK cell activity, we examined interacting NK cells and blood cancer cells using single-cell…
View article: Knockout of the inhibitory receptor TIGIT enhances the antitumor response of ex vivo expanded NK cells and prevents fratricide with therapeutic Fc-active TIGIT antibodies
Knockout of the inhibitory receptor TIGIT enhances the antitumor response of ex vivo expanded NK cells and prevents fratricide with therapeutic Fc-active TIGIT antibodies Open
Background Inhibitory receptor T-cell Immunoreceptor with Ig and ITIM domains (TIGIT) expressed by Natural Killer (NK) and T cells regulates cancer immunity and has been touted as the next frontier in the development of cancer immunotherap…
View article: High-Throughput Screens Identify NEDD8 Inhibition As a Strategy to Augment Natural Killer Cell Cytotoxicity Against Blood Cancers
High-Throughput Screens Identify NEDD8 Inhibition As a Strategy to Augment Natural Killer Cell Cytotoxicity Against Blood Cancers Open
Natural killer (NK) cell-based therapies are amongst the emerging immunotherapeutic approaches that aim to target malignant cells refractory to standard therapies. Currently used strategies to augment the NK cell anti-cancer function of NK…
View article: S256: HLA-E/NKG2A CHECKPOINT DRIVES MULTIPLE MYELOMA RESISTANCE TO CAR-NK THERAPY
S256: HLA-E/NKG2A CHECKPOINT DRIVES MULTIPLE MYELOMA RESISTANCE TO CAR-NK THERAPY Open
Background: HLA-E is highly expressed in several tumor cells, including metastatic cells, and correlates with a poor prognosis. Its interaction with the inhibitory receptor NKG2A, expressed in T lymphocytes and NK cells, enables tumor cell…