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1.
Cell Immunol ; 399-400: 104827, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38733699

RESUMO

The need to contrive interventions to curb the rise in cancer incidence and mortality is critical for improving patients' prognoses. Adoptive cell therapy is challenged with quality large-scale production, heightening its production cost. Several cancer types have been associated with the expression of highly-immunogenic CTAG1 and CTAG2 antigens, which share common epitopes. Targeting two antigens on the same cancer could improve the antitumor response of TCR-T cells. In this study, we exploited an efficient way to generate large-fold quality TCR-T cells and also demonstrated that the common epitopes of CTAG1 and CTAG2 antigens provide an avenue for improved cancer-killing via dual-antigen-epitope targeting. Our study revealed that xeno/sera-free medium could expand TCR-T cells to over 500-fold, posing as a better replacement for FBS-supplemented media. Human AB serum was also shown to be a good alternative in the absence of xeno/sera-free media. Furthermore, TCR-T cells stimulated with beads-coated T-activator showed a better effector function than soluble T-activator stimulated TCR-T cells. Additionally, TCR-T cells that target multiple antigens in the same cancer yield better anticancer activity than those targeting a single antigen. This showed that targeting multiple antigens with a common epitope may enhance the antitumor response efficacy of T cell therapies.


Assuntos
Antígenos de Neoplasias , Imunoterapia Adotiva , Receptores de Antígenos de Linfócitos T , Antígenos de Neoplasias/imunologia , Humanos , Imunoterapia Adotiva/métodos , Receptores de Antígenos de Linfócitos T/imunologia , Animais , Epitopos de Linfócito T/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Camundongos , Linhagem Celular Tumoral , Linfócitos T/imunologia , Epitopos/imunologia
2.
Nat Commun ; 15(1): 583, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233381

RESUMO

In contrast to rodents, the mechanisms underlying human trophectoderm and early placenta specification are understudied due to ethical barriers and the scarcity of embryos. Recent reports have shown that human pluripotent stem cells (PSCs) can differentiate into trophectoderm (TE)-like cells (TELCs) and trophoblast stem cells (TSCs), offering a valuable in vitro model to study early placenta specification. Here, we demonstrate that the VGLL1 (vestigial-like family member 1), which is highly expressed during human and non-human primate TE specification in vivo but is negligibly expressed in mouse, is a critical regulator of cell fate determination and self-renewal in human TELCs and TSCs derived from naïve PSCs. Mechanistically, VGLL1 partners with the transcription factor TEAD4 (TEA domain transcription factor 4) to regulate chromatin accessibility at target gene loci through histone acetylation and acts in cooperation with GATA3 and TFAP2C. Our work is relevant to understand primate early embryogenesis and how it differs from other mammalian species.


Assuntos
Células-Tronco Pluripotentes , Fatores de Transcrição , Gravidez , Feminino , Humanos , Camundongos , Animais , Linhagem da Célula/genética , Fatores de Transcrição/genética , Trofoblastos/fisiologia , Diferenciação Celular/genética , Mamíferos , Primatas , Proteínas de Ligação a DNA/genética , Fatores de Transcrição de Domínio TEA
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