Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Since there are also some challenges beyond the TME that are important for CAR function, we will also discuss and provide data about the improvement of CAR T cells trafficking and delivery to the tumor site and how to solve the problem of tumor antigen heterogeneity.
|
31161552 |
2019 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Selective anti-tumor activity in the absence of toxicity provides proof-of-concept that micromolar affinity tuned CAR T cells can be used to target tumors expressing high levels of antigen while avoiding normal tissues expressing basal levels of the same antigen.
|
31337787 |
2019 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
However, their broad use is limited since a CAR targets a single tumor associated antigen (TAA), which is not effective against tumors with heterogeneous TAA expression or emerging antigen loss variants.
|
30984613 |
2019 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Recent studies have demonstrated that aberrantly glycosylated cell surface proteins on tumor cells are amenable CAR targets.
|
30510550 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In this study, we engineered T cells with a CAR consisting of the extracellular domain of heregulin-1β (HRG1β) that is a natural ligand for HER3/HER4, and evaluated the specific cytotoxicity of these CAR-T cells in cultured HER3 positive breast cancer cells and xenograft tumors.
|
29127433 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Ad-mTNFa-mIL2 increased both CAR T cell and host T cell infiltration to the tumor and altered host tumor immune status with M1 polarization of macrophages and increased dendritic cell maturation.
|
29618658 |
2018 |
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Moreover, CD19-GITR-CD3 CAR-T cells had significant cytotoxic activity against CD19-positive cancer cells <i>in vitro</i> and in Raji xenograft tumors <i>in vivo</i>.
|
29772559 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Treatment with GSK3-inhibited CAR-T cells resulted in 100% tumor elimination during the tumor-rechallenge experiment in GBM-bearing animals and increased accumulation of memory CAR-T cells in secondary lymphoid organs.
|
29959057 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The obstacles that reduce the efficacy of CAR-T therapy in solid tumors include a lack of specific tumor antigens, limited trafficking and penetration of CAR-T cells to tumor sites, and an immunosuppressive tumor microenvironment.
|
29861325 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The results indicated that the disruption of PD-1 enhanced the <i>in vivo</i> anti-tumor activity of CAR T cells against HCC, improved the persistence and infiltration of CAR T cells in the NSG mice bearing the tumor, and strengthened the inhibition of tumor-related genes expression in the xenograft tumors caused by the GPC3-CAR T cells.
|
30327605 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
CAR T cell therapy has shown stunning results especially in B-cell malignancies; however, it has shown less success against solid tumors, which is more supposed to be related to the specific characteristics of the tumor microenvironment.
|
30108584 |
2018 |
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
In a mouse model, EwS xenografts after adoptive therapy with tumor antigen-specific CAR T cells strongly expressed HLA-G whereas untreated control tumors were HLA-G<sup>neg</sup>.
|
29464090 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In addition, effects on the function of the CAR-T cells that the space distance between the antigen binding domains and tumor targets and the length of the spacer domains have are also being investigated.
|
29568411 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
CAR is found in normal epithelial cells and is increased in abundance in various human tumors, including lung carcinomas.
|
29382784 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Inclusion of the CD137 (4-1BB) costimulatory intracellular domain in the M27-28BBZ CAR provided CAR T cells with higher tumor lysis activity than when not included (as in the M27-28Z CAR).
|
30201736 |
2018 |
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Even though hundreds of clinical trials are undergoing exploring a variety of tumor-associated antigens (TAA), no such antigen with comparable properties like CD19 has yet been identified regarding solid tumors CAR-T immunotherapy.
|
29433552 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We also evaluated HER2-CAR T cells delivered by intravenous, local intratumoral, or regional intraventricular routes of administration using <i>in vivo</i> human xenograft models of breast cancer that have metastasized to the brain.<b>Results:</b> Here, we have shown that HER2-CARs containing the 4-1BB costimulatory domain confer improved tumor targeting with reduced T-cell exhaustion phenotype and enhanced proliferative capacity compared with HER2-CARs containing the CD28 costimulatory domain.
|
29061641 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In addition, scFV-3H11 CAR-T cells are able to kill tumor cells accompanied with increased interleukin-2 and interferon-γ secretion <i>in vitro</i>, and reduced the tumor burden in GC cell lines and patient-derived GC cells <i>in vivo</i>.
|
29849787 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
One limiting factor of CAR T-cell therapy for treatment of solid cancers is the suppressive tumor microenvironment (TME), which inactivates the function of tumor-infiltrating lymphocytes (TIL) through the production of immunosuppressive molecules, such as adenosine.
|
29720380 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
By comparison, the CD4+ CAR T cells persisted after tumor challenge and sustained their effector potency.
|
29769444 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
IP delivery of CAR-T cells has shown demonstrable suppression of tumors expressing carcinoembryonic antigen.
|
30103457 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Advancing the use of adoptively transferred T cells for the treatment of patients with solid tumor and other hematologic malignancies however, will require addressing numerous effector cell intrinsic as well as tumor micro environmental hurdles and exploiting a broader ACT platform that includes not only engineered CAR-T cells, but also other forms of ACT including Endogenous T Cell (ETC) and Tumor-infiltrating Lymphocyte (TIL) therapy.
|
29730057 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
A homologous, all murine anti-CD70 CAR model was also used to assess treatment-related toxicities.<b>Results:</b> The CAR consisting of the extracellular binding portion of CD27 fused with 41BB and CD3-zeta (trCD27-41BB-zeta) conferred the highest IFNγ production against CD70-expressing tumors <i>in vitro</i>, and NSG mice bearing established CD70-expressing human tumors could be cured by human lymphocytes transduced with this CAR.
|
27803044 |
2017 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors more effectively than does systemic delivery of the same cells.
|
28436934 |
2017 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In this study, we evaluated in human tumor xenograft models the proinflammatory properties of an oncolytic adenovirus (Onc.Ad) with a helper-dependent Ad (HDAd) that expresses a PD-L1 blocking mini-antibody (mini-body; HD<i>PDL1</i>) as a strategy to enhance CAR T-cell killing.
|
28235763 |
2017 |