Aquí, Demostramos que la Trabectedina Induce la Apoptosis de las Células Leucémicas Primarias Humanas y también las Células Inmunosupresoras Mieloides y Linfoides seleccionadas, Principalmente a través de la Vía TRAIL / TNF.
Yondelis® Bloquea el eje PD-1 / PD-L1 Dirigiéndose a las Células PD-L1 + CLL, los Monocitos / Macrófagos PD-L1 + y las Células T PD-1 + .
Por lo tanto, la Trabectedin se Comporta como un Fármaco Inmunomodulador con un Valor Terapéutico Potencialmente Atractivo en la Subversión del Microambiente del Tumor y en la Superación de la Resistencia Quimioinmune.
©2019 American Association for Cancer Research.
Priyanka Banerjee, Ronghua Zhang, Cristina Ivan, Giovanni Galletti, Karen Clise-Dwyer, Federica Barbaglio, Lydia Scarfò, Miguel Aracil, Christian Klein, William Wierda, William Plunkett, Federico Caligaris-Cappio, Varsha Gandhi, Michael J. Keating and Maria Teresa S. Bertilaccio
Published December 2019 .
Abstract:
Chronic Lymphocytic Leukemia (CLL) is a B-Cell Neoplasia Characterized by protumor Immune Fysregulation involving nonmalignant cells of the Microenvironment, including T lymphocytes and Tumor-associated Myeloid cells.
Ather Therapeutic Agents have Improved Treatment Options for CLL, many Patients still Fail to Respond. Some Patients also show Immunosuppression. We have investigated Trabectedin, a marine-derived compound with Cytotoxic Activity on Macrophages in solid tumors. Here, we demonstrate that Trabectedin induces Apoptosis of human primary Leukemic cells and also selected Myeloid and Lymphoid Immunosuppressive cells, mainly through the TRAIL/TNF pathway.
Trabectedin Modulates transcription and translation of IL6, CCL2, and IFNα in myeloid cells and FOXP3 in regulatory T cells. Human memory CD8+ T cells downregulate PD-1 and, along with monocytes, exert in vivo antitumor function. In xenograft and immunocompetent CLL mouse models, Trabectedin has Antileukemic effects and antitumor impact on the Myeloid and Lymphoid cells compartment. It depletes myeloid-derived suppressor cells and tumor-associated Macrophages and increases memory T cells. T
Trabectedin Also blocks the PD-1/PD-L1 axis by targeting PD-L1+ CLL cells, PD-L1+ Monocytes/Macrophages, and PD-1+ T cells.
Thus Trabectedin behaves as an Immunomodulatory Drug with Potentially attractive therapeutic value in the subversion of the Protumor Microenvironment and in Overcoming Chemoimmune Resistance.
********************************
De Hecho ya existe esta Nueva Expectativa para Yondelis Gracias a su Manera de Actuar de la mano del M.D. Anderson Cancer Center y el NCI :
MD Anderson Cancer Center como Patrocinador en Colaboración con el Instituto Nacional del Cáncer US ( NCI ) Llevarán a Cabo un Ensayo Clínico con Yondelis en Combinación con Venclexta™ en el Tratamiento de Pacientes con Leucemia Linfocítica Crónica o Linfoma Linfocítico Pequeño Resistente o Intolerante a un Inhibidor de BTK .Study Status :
Overall Status : Recruiting .
Study Start : June 18, 2019 .
Primary Completion : April 9, 2020
Sposor/Collaborators :
Sponsor : M.D. Anderson Cancer Center .
Responsible Party : Sponsor .
Collaborators : National Cancer Institute (NCI) .