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Targeting CD44 and EpCAM with Antibody Dye Conjugates for the Photoimmunotherapy of Prostate Cancer.
Antibodies (Basel)
January 2025
Department of Urology, Medical Center-University of Freiburg, 79106 Freiburg im Breisgau, Germany.
Background/objectives: Photoimmunotherapy (PIT) is an innovative approach for the targeted therapy of cancer. In PIT, photosensitizer dyes are conjugated to tumor-specific antibodies for targeted delivery into cancer cells. Upon irradiation with visible light, the photosensitizer dye is activated and induces cancer-specific cell death.
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 PDFInitial clinical experience with [Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer: dosimetry, safety, and efficacy from the lead-in cohort of the SPLASH trial.
Front Oncol
January 2025
Department of Clinical Development, POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company, Indianapolis, IN, United States.
Introduction: SPLASH (NCT04647526) is a multicenter phase III trial evaluating the efficacy and safety of [Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC). This study leveraged a lead-in phase to assess tissue dosimetry and evaluate preliminary safety and efficacy, prior to expansion into a randomized phase. Here we report those results.
View Article and Find Full Text PDFA Universal Therapeutic Vaccine Leveraging Autologous Pre-Existing Immunity to Eliminate in Situ Uniformly Engineered Heterogeneous Tumor Cells.
Adv Mater
January 2025
Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, P. R. China.
Tumor vaccines that activate the autologous immune system to eliminate tumor cells represent a promising approach in cancer immunotherapy. However, challenges such as tumor heterogeneity, limited antigen selection, insufficient antigen presentation, and the slow onset of de novo immune responses have resulted in poor universality and suboptimal response rates. In contrast, pathogen-specific pre-existing immunity acquired through infection or vaccination, can rapidly generate a more potent and enduring immune response upon re-encounter with the same antigen.
View Article and Find Full Text PDFAdvances in CAR T cell therapy: antigen selection, modifications, and current trials for solid tumors.
Front Immunol
January 2025
Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies, achieving remarkable clinical success with FDA-approved therapies targeting CD19 and BCMA. However, the extension of these successes to solid tumors remains limited due to several intrinsic challenges, including antigen heterogeneity and immunosuppressive tumor microenvironments. In this review, we provide a comprehensive overview of recent advances in CAR T cell therapy aimed at overcoming these obstacles.
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