The generation of antibodies following exposure to therapeutic drugs has been widely studied, however in oncology, data in relation to their clinical relevance are limited. Antidrug antibodies (ADAs) can cause a decrease in the amount of drug available, resulting in some cases in decreased antitumor activity and a consequent impact on clinical outcomes. Several immunologic factors can influence the development of ADAs, and in addition, the sensitivity of the different testing methods used in different studies can vary, representing an additional potential confounding factor. The reported frequency of ADA-positive patients following treatment with immune checkpoint inhibitors varies from as low as 1.5% for pembrolizumab to 54% for atezolizumab. This latter drug is the only immune checkpoint inhibitor to have undergone an expanded analysis of the clinical implications of ADAs, but with discordant results. Given that immune checkpoint inhibitors can modify the immune response and potentially impact ADA formation, data from published as well as prospective trials need to be evaluated for a better understanding of the clinical implications of ADAs in this setting.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-2337 | DOI Listing |
Am J Clin Dermatol
January 2025
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
Individualized neoantigen-directed therapy represents a groundbreaking approach in melanoma treatment that leverages the patient's own immune system to target cancer cells. This innovative strategy involves the identification of unique immunogenic neoantigens (mutated proteins specific to an individual's tumor) and the development of therapeutic vaccines that either consist of peptide sequences or RNA encoding these neoantigens. The goal of these therapies is to induce neoantigen-specific immune responses, enabling the immune system to recognize and destroy cancer cells presenting the targeted neoantigens.
View Article and Find Full Text PDFPharmacoecon Open
January 2025
Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Objectives: Immune checkpoint inhibitor (ICI)-containing treatment is currently prescribed as first-line treatment for all patients with advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, only 30-45% of patients show no progression within 12 months after treatment start. Various biomarkers are being studied to save costly and potentially harmful treatment in non-responders.
View Article and Find Full Text PDFCancer Metastasis Rev
January 2025
Département de Radiothérapie et de Physique Médicale, Centre Henri Becquerel Rouen QuantiF, LITIS EA4108 Université Rouen, Rouen, France.
The management of bone metastases (BoM) requires a multidisciplinary approach to prevent complications, necessitating updated knowledge in light of the rapid advancements in systemic treatments and surgical, interventional radiology or radiation techniques. This review aims to discuss efficacy of new systemic treatments on BoM, the benefits of radiotherapy adjunction, and the optimal methods for combining them. Preliminary evidence suggesting reduced efficacy of immune checkpoint inhibitors (ICI), and several multi-kinase inhibitors regarding BoM may encourage early use of radiotherapy (RT).
View Article and Find Full Text PDFCell Death Differ
January 2025
Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Hyperactivation of the YAP/TEAD transcriptional complex in cancers facilitates the development of an immunosuppressive tumor microenvironment. Herein, we observed that the transcription factor SP1 physically interacts with and stabilizes the YAP/TEAD complex at regulatory genomic loci in colorectal cancer (CRC). In response to serum stimulation, PKCζ (protein kinase C ζ) was found to phosphorylate SP1 and enhance its interaction with TEAD4.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Rapa Therapeutics, Rockville, Maryland, USA.
Background: Polyclonal autologous T cells that are epigenetically reprogrammed through mTOR inhibition and IFN-α polarization (RAPA-201) represent a novel approach to the adoptive T cell therapy of cancer. Ex vivo inhibition of mTOR results causes a shift towards T central memory (T) whereas ex vivo IFN-α promotes type I cytokines, with each of these functions known to enhance the adoptive T cell therapy of cancer. Rapamycin-resistant T cells polarized for a type II cytokine phenotype were previously evaluated in the allogeneic transplantation context.
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