Antibody–Drug Conjugates—Evolution and Perspectives

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 6969 - 6969

Published: June 26, 2024

Antineoplastic therapy is one of the main research themes this century. Modern approaches have been implemented to target and heighten effect cytostatic drugs on tumors diminish their general/unspecific toxicity. In context, antibody-drug conjugates (ADCs) represent a promising successful strategy. The aim review was assess different aspects regarding ADCs. They were presented from chemical pharmacological perspective like structure, conjugation development particularities alongside effects, clinical trials, safety issues perspectives challenges for future use these discussed. Representative examples include but are not limited following structural components ADCs: monoclonal antibodies (trastuzumab, brentuximab), linkers (pH-sensitive, reduction-sensitive, peptide-based, phosphate-based, others), payloads (doxorubicin, emtansine, ravtansine, calicheamicin). Regarding pharmacotherapy success, high effectiveness expectation associated with ADC treatment supported by large number ongoing trials. Major such as strategies first discussed, advantages disadvantages, efficacy, offering retrospective insight subject. second part prospective, focusing various plans overcome previously identified difficulties.

Language: Английский

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Novel Targets and Advanced Therapies in Diffuse Large B Cell Lymphomas

Cancers, Journal Year: 2024, Volume and Issue: 16(12), P. 2243 - 2243

Published: June 17, 2024

Since the introduction of rituximab in late 1990s, significant progress has been made advancing targeted therapies for B cell lymphomas, improving patients’ chance being cured and clinicians’ therapeutic armamentarium. A better understanding disease biology pathogenic pathways, coupled with refinements immunophenotypic molecular diagnostics, have instrumental these achievements. While traditional chemotherapy remains fundamental most cases, concerns surrounding chemorefractoriness cumulative toxicities, particularly depletion hemopoietic reserve, underscore imperative personalized treatment approaches. Integrating agents, notably monoclonal antibodies, alongside yielded heightened response rates prolonged survival. notable paradigm shift is underway innovative-targeted replacing cytotoxic drugs, challenging conventional salvage strategies like stem transplantation. This review examines landscape emerging targets lymphoma cells explores innovative diffuse large (DLBCL). From Chimeric Antigen Receptor-T to more potent antibody–drug conjugates, bispecific checkpoint inhibitors, small molecules targeting intracellular each modality offers promising avenues advancement. aims furnish insights into their potential implications future DLBCL strategies.

Language: Английский

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Disulfidptosis: A Novel Prognostic Criterion and Potential Treatment Strategy for Diffuse Large B-Cell Lymphoma (DLBCL)

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7156 - 7156

Published: June 28, 2024

Diffuse Large B-cell Lymphoma (DLBCL), with its intrinsic genetic and epigenetic heterogeneity, exhibits significantly variable clinical outcomes among patients treated the current standard regimen. Disulfidptosis, a novel form of regulatory cell death triggered by disulfide stress, is characterized collapse cytoskeleton proteins F-actin due to intracellular accumulation disulfides. We investigated expression variations disulfidptosis-related genes (DRGs) in DLBCL using two publicly available gene datasets. The initial analysis DRGs (GSE12453) revealed differences patterns between various normal B cells DLBCL. Subsequent (GSE31312) identified strongly associated prognostic outcomes, revealing eight characteristic (CAPZB, DSTN, GYS1, IQGAP1, MYH9, NDUFA11, NDUFS1, OXSM). Based on these DRGs, were stratified into three groups, indicating that (1) can predict prognosis, (2) help identify therapeutic candidates. This study underscores significant role biological processes within Assessing risk scores individual allows for more precise stratification prognosis treatment strategies patients, thereby enhancing effectiveness practice.

Language: Английский

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The potential of antibody-drug conjugates for effective therapy in diffuse large B-cell lymphoma

Expert Opinion on Biological Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Introduction Antibody-drug conjugates (ADCs) are a rapidly evolving class of anti-cancer drugs with significant impact on management hematological malignancies including diffuse large B-cell lymphoma (DLBCL). ADCs combine cytotoxic drug (a.k.a. payload) attached through linker to monoclonal antibody specific particular cancer antigen. Payloads include microtubule disruptors or DNA damaging chemicals. After attaching the antigen, internalized, and payload is dissociated from ADC by lysozymes delivered intended site for exerting effects. This unique molecular design permits better balance efficacy safety. Loncastuximab tesirine polatuzumab vedotin two approved in U.S.A. treatment DLBCL.

Language: Английский

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Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11384 - 11384

Published: Oct. 23, 2024

Diffuse large B-cell lymphoma (DLBCL) is a malignancy of immense biological and clinical heterogeneity. Based on the transcriptomic or genomic approach, several different classification schemes have evolved over years to subdivide DLBCL into clinically (prognostically) relevant subsets, but each leaves unclassified samples. Herein, we outline tumor biology behind actual potential drug targets address challenges drawbacks coupled with their (potential) use. Therapeutic modalities are discussed, including small-molecule inhibitors, naked antibodies, antibody-drug conjugates, chimeric antigen receptors, bispecific antibodies T-cell engagers, immune checkpoint inhibitors. Candidate drugs explored in ongoing trials diverse toxicity issues refractoriness drugs. According literature DLBCL, promise for new therapeutic lies epigenetic alterations, receptor NF-κB pathways. present putative hiding lipid pathways, ferroptosis, gut microbiome that could be used addition immuno-chemotherapy improve general health status patients, thus increasing chance being cured. It may time devote more effort exploring metabolism discover novel druggable targets. We also performed bibliometric knowledge-map analysis published from 2014-2023.

Language: Английский

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Hepatopulmonary syndrome associated with long-term use of ado-trastuzumab emtansine (T-DM1) for treatment of HER2-positive metastatic breast cancer - a case report and series

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Oct. 21, 2024

Background The advent of antibody-drug conjugates (ADCs) represents a landmark advance in cancer therapy, permitting targeted delivery potent cytotoxic agent to tumor cells with minimal damage surrounding cells. Although ADCs can induce sustained therapeutic responses heavily pretreated patients, they also cause significant toxicity and thus require careful monitoring. prototype ADC, ado-trastuzumab emtansine (T-DM1) is comprised humanized, monoclonal human epidermal growth factor receptor 2 (HER2)-directed antibody, trastuzumab, linked the agent, DM1, used for treatment early-stage advanced HER2-positive breast cancer. Liver toxicities, including transaminitis nodular regenerative hyperplasia resulting portal hypertension have been described. We report case series four patients who developed hepatopulmonary syndrome (HPS) during T-DM1. HPS characterized by hypoxemia, hypertension, intrapulmonary shunting, it be associated severe hypoxic respiratory failure. secondary noncirrhotic occurring long-term exposure T-DM1 has not previously reported. Case presentation Four received our institutional cohort (n=230) HPS, which Each patient diagnosed >50 doses Only one at diagnosis had resting hypoxia, while other three became exertion only. Discontinuation led clinical improvement hypoxia patients. spectrum liver injury that occurs use remains incompletely defined. Conclusions As approved management operable cancer, awareness as potential complication administration necessary. emergence dyspnea alone or combined low oxygen saturation signs hypoxemia (clubbing elevated hemoglobin) should raise suspicion prompt evaluation HPS. Cancer care team members vigilant regarding new serious side effects novel therapies, may emerge years beyond initial regulatory approval.

Language: Английский

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Determination of the decapping efficiency of THIOMAB™ antibodies with the engineered cysteine in the Fc region for making antibody–drug conjugates by specific hinge fragmentation-liquid chromatography

Analytical and Bioanalytical Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Language: Английский

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