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Cell-Based Therapies in GI Cancers: Current Landscape and Future Directions.
Am Soc Clin Oncol Educ Book
January 2025
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Cell-based therapies have become integral to the routine clinical management of hematologic malignancies. Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated efficacy in immunogenic solid tumors, such as melanoma. However, in the GI field, evidence supporting the clinical success of cell-based therapies is still awaited.
View Article and Find Full Text PDFMicroenvironment actuated CAR T cells improve solid tumor efficacy without toxicity.
Sci Adv
January 2025
Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
A major limiting factor in the success of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors is targeting tumor antigens also found on normal tissues. CAR T cells against GD2 induced rapid, fatal neurotoxicity because of CAR recognition of GD2 normal mouse brain tissue. To improve the selectivity of the CAR T cell, we engineered a synthetic Notch receptor that selectively expresses the CAR upon binding to P-selectin, a cell adhesion protein overexpressed in tumor neovasculature.
View Article and Find Full Text PDFTriple knockdown of , , and in T cells reduces CAR-T cell toxicity but preserves activity against solid tumors in mice.
Sci Transl Med
January 2025
Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Chimeric antigen receptor (CAR)-T cell therapies have revolutionized the landscape of cancer treatment, in particular in the context of hematologic malignancies. However, for solid tumors that lack tumor-specific antigens, CAR-T cells can infiltrate and attack nonmalignant tissues expressing the CAR target antigen, leading to on-target, off-tumor toxicity. Severe on-target, off-tumor toxicities have been observed in clinical trials of CAR-T therapy for solid tumors, highlighting the need to address this issue.
View Article and Find Full Text PDFSafety of two-dose schedule of COVID-19 adsorbed inactivated vaccine (CoronaVac; Sinovac/Butantan) and heterologous additional doses of mRNA BNT162b2 (Pfizer/BioNTech) in immunocompromised and immunocompetent individuals.
Rev Inst Med Trop Sao Paulo
January 2025
Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Divisão de Clínica de Moléstias Infecciosas e Parasitárias, Laboratório de Investigação Médica em Imunologia (LIM-48), SSão Paulo, São Paulo, Brazil.
Immunocompromised individuals were considered high-risk for severe disease due to SARS COV-2 infection. This study aimed to describe the safety of two doses of COVID-19 adsorbed inactivated vaccine (CoronaVac; Sinovac/Butantan), followed by additional doses of mRNA BNT162b2 (Pfizer/BioNTech) in immunocompromised (IC) adults, compared to immunocompetent/healthy (H) individuals. This phase 4, multicenter, open label study included solid organ transplant and hematopoietic stem cell transplant recipients, cancer patients and people with inborn errors of immunity with defects in antibody production, rheumatic, end-stage chronic kidney or liver disease, who were enrolled in the IC group.
View Article and Find Full Text PDFExploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma.
PLoS One
January 2025
Department of Pathology, Yale School of Medicine, Yale University, New Haven, Connecticut, United States of America.
Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and the second leading cause of cancer-related mortality globally. Despite advancements in current HCC treatment, it remains a malignancy with poor prognosis. Therefore, developing novel treatment options for patients with HCC is urgently needed.
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