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Query: UMLS:C0406810 (
NAME
)
13,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Our recent clinical study demonstrated that glypican-3 (GPC3)-specific chimeric antigen receptor-modified T (CAR-T) cells are a promising treatment for hepatocellular carcinoma (HCC). However, the interaction of
programmed cell death 1
(
PD-1
) and PD-L1-mediated T-cell inhibition is involved in immune evasion in a wide range of solid tumors, including HCC. To overcome this problem, we introduced a fusion protein composed of a
PD-1
extracellular domain and CH3 from IgG4 into GPC3-specific
CAR
-T cells (GPC3-28Z) to block the
PD-1
/PD-L1 pathway. GPC3-specific
CAR
-T cells carrying the
PD-1
-CH3 fusion protein (sPD1) specifically recognized and lysed GPC3-positive HCC cells. The proliferation capacity of GPC3-28Z-sPD1 T cells after weekly stimulation with target cells was much higher than that of control GPC3-28Z T cells. Additionally, the coexpression of sPD1 could protect
CAR
-T cells from exhaustion when incubated with target cells, as phosphorylated AKT and Bcl-xL expression levels were higher in GPC3-28Z-sPD1 T cells than in GPC3-28Z cells. Importantly, in two HCC tumor xenograft models, GPC3-28Z-sPD1 T cells displayed a significantly higher tumor suppression capacity than GPC3-28Z T cells. In addition, an increased number of CD3
+
T cells in the circulation and tumors and increased granzyme B levels and decreased Ki67 expression levels in the tumors were observed in the mice treated with GPC3-28Z-sPD1 T cells. Together, these data indicated that GPC3-specific
CAR
-T cells carrying sPD1 show promise as a treatment for patients with HCC.
...
PMID:Increased antitumor activities of glypican-3-specific chimeric antigen receptor-modified T cells by coexpression of a soluble PD1-CH3 fusion protein. 3007 52
Anti-CD19 chimeric antigen receptor T cell (CAR-T) therapy has changed the typical outcomes of relapsed/refractory B-cell leukemia and lymphoma. However, treatment effectiveness for patients with relapsed/refractory B-cell non-Hodgkin lymphoma has been less satisfactory compared with patients with B-cell acute lymphoblastic leukemia. The present study described a case of refractory follicular lymphoma. A high expression of
programmed cell death 1
(
PD-1
) was measured on CD3
+
T cells (80.90%) in peripheral blood samples obtained from the patient enrolled in this study, indicating that treatment with autologous
CAR
-T 19 cell therapy may not be successful. Therefore, a therapy regimen consisting of
CAR
-T 19 cells in combination with a reduced dose of nivolumab (1.5 mg/kg) for
PD-1
blockade was used. A low dose of
PD-1
blockade therapy was used to reduce the adverse effects associated with the combination of a
PD-1
inhibitor and
CAR
-T 19 cells. This salvage therapy resulted in remission that lasted for >10 months.
...
PMID:CAR-T 19 combined with reduced-dose PD-1 blockade therapy for treatment of refractory follicular lymphoma: A case report. 3161 50
Introduction
: Lung cancer is a devastating disease with poor overall survival. Despite significant advances in the treatment of lung cancers using radiochemotherapy, targeted therapies and/or immune therapies prognosis remains poor. The capacity of natural killer (NK) cells to provide a first line of defense that can bridge and orchestrate innate and 'downstream' adaptive immune responses renders them to be an ideal platform on which to base new cancer therapeutics.
Areas covered
: We provide an overview of the mechanisms controlling the effector functions of NK cells, tumor-directed immune escape, the impact and influence of NK cells on the development of effective, protective anti-tumor immunity and the therapeutic potential of combined cytokine-, complement-dependent- and antibody-dependent cellular cytotoxicity (CDC/ADCC), NK-92-, KIR mismatch- and
CAR
-NK cell-based therapies.
Expert opinion
: Despite promising results of immuno-oncological approaches, a relevant proportion of patients do not profit from these therapies, partly due to an ineffective NK cell activation, a lack of tumor-specific NK cells, an upregulated expression of checkpoint pathways, and a low mutational burden, which hinders the development of long-term adaptive immunity. Strategies that re-activate NK cells in combination with other therapies are therefore likely to be beneficial for the clinical outcome of patients with lung cancer.
Abbreviations:
ADCC: antibody-dependent cell-mediated cytotoxicity; ALK: anaplastic lymphoma kinase;
CAR
: chimeric antigen receptor; CDC: complement-dependent cytotoxicity; CEACAM-1: carcinoembryonic antigen-related cell adhesion molecule 1; DC: dendritic cell; DNAM: activating, maturation receptor; EGFR, epidermal growth factor receptor; EMT: epithelial-to-mesenchymal transition; EpCAM: epithelial cell adhesion molecule; GM-CSF: granulocyte monocyte colony stimulating factor; HIF: hypoxia inducible factor; IDO, indoleamine 2,3-dioxygenase; IFN: interferon; IL: interleukin; ITIM/ITAM: immune tyrosine-based inhibitory/activatory motif; KIR: killer cell immunoglobulin-like receptor; LAG-3: lymphocyte activation gene 3; MDSC: myeloid derived suppressor cells; MICA/B: MHC class I-related proteins A/B; MHC: major histocompatibility complex; mTOR: mechanistic target of rapamycin; NCAM: neuronal adhesion molecule; NCR: natural cytotoxicity receptor; NK: natural killer; NSCLC: non-small cell lung cancer; PD-1:
programmed cell death 1
; PS: phosphatidylserine; SCLC: small cell lung cancer; STAT: signal transducer and activator of transcription; TAM: tumor-associated M2 macrophages; TCR: T cell receptor; TIGIT: T cell immunoglobulin and ITIM domain; Tim-3: T cell immunoglobulin- and mucin domain-containing 3; TNF: tumor necrosis factor; ULBP: UL16-binding protein.
...
PMID:NK cell-based therapeutics for lung cancer. 3171 56
