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CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia
TLDR
Preclinical studies show potent activity of CART33 and indicate that transient expression of anti-CD33 CAR by RNA modification could be used in patients to avoid long-term myelosuppression.
CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo.
TLDR
CD27 costimulation enhances expansion, effector function, and survival of human CAR-T cells in vitro and augments human T-cell persistence and antitumor activity in vivo.
CD137 Accurately Identifies and Enriches for Naturally Occurring Tumor-Reactive T Cells in Tumor
TLDR
A role for the TNFR-family member CD137 is revealed in the immunobiology of human cancer where it is preferentially expressed on tumor-reactive subset of TILs, thus rationalizing its agonistic engagement in vivo and its use in TIL selection for adoptive immunotherapy trials.
Chimeric Antigen Receptor T Cells with Dissociated Signaling Domains Exhibit Focused Antitumor Activity with Reduced Potential for Toxicity In Vivo
TLDR
A trans-signaling CAR-based immunotherapy strategy in which the T-cell activation signal is physically dissociated from the costimulatory signal in two CARs of differing antigen specificity can potentiate the therapeutic efficacy of CAR-T cells against cancer while minimizing parallel reactions against normal tissues bearing single antigen.
In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137 (4-1BB).
TLDR
Results show that anti-FRα CAR outfitted with CD137 costimulatory signaling in tandem overcome issues of T-cell persistence and tumor localization that limit the conventional FRα T- cell targeting strategy to provide potent antitumor activity in vivo.
Pro-survival signaling via CD27 costimulation drives effective CAR T-cell therapy
TLDR
This work investigated whether CD27 signaling augments antigen redirected human T-cell survival, expansion and function in vitro and in vivo.
Chimeric NKG2D CAR-expressing T cell-mediated attack of human ovarian cancer is enhanced by histone deacetylase inhibition.
TLDR
It is demonstrated that VPA-induced upregulation ofNKG2DL expression enhances the immune recognition of ovarian cancer cells by engineered NKG2D CAR T cells, and rationalizes the use of VPA in combination with NKG 2DL-targeted immunotherapy in ovarian cancer.
Rigorous optimization and validation of potent RNA CAR T cell therapy for the treatment of common epithelial cancers expressing folate receptor
TLDR
This work utilized a non-integrating RNA platform to engineer human T cells to express FRα-specific, CD27 CARs and tested their capacity to eliminate human FRα+ cancer, establishing a new paradigm for preclinical optimization and validation of RNA CAR candidates destined for clinical translation.
Effective adoptive immunotherapy of triple-negative breast cancer by folate receptor-alpha redirected CAR T cells is influenced by surface antigen expression level
TLDR
Results show that FRα CAR T cells can mediate antitumor activity against established TNBC tumor, particularly when FRα is expressed at higher levels, which has significant implications for the pre-selection of patients with high antigen expression levels when utilizing CAR-based adoptive T cell therapies of cancer in future clinical trials.
Control of triple-negative breast cancer using ex vivo self-enriched, costimulated NKG2D CAR T cells
TLDR
These results demonstrate that CD27 or 4-1BB costimulated, self-enriched NKG2D CAR-redirected T cells mediate anti-tumor activity against TNBC tumor, which represent a promising immunotherapeutic approach to TNBC treatment.
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