Antibody-Drug Conjugates in Breast Cancer: Toward a Molecular Perspective Into Clinical Practice DOI
Roberto Paz-Manrique, Joseph A. Pinto, Guillermo Valencia

et al.

JCO Precision Oncology, Journal Year: 2024, Volume and Issue: 8

Published: Oct. 1, 2024

Antibody-drug conjugates (ADCs) are at the forefront of cancer therapy, combining targeted precision with potent cytotoxicity. Conceived by Paul Ehrlich in early 1900s, concept a magic bullet selectively eliminating cells has evolved alongside bioengineering and biology advancements. ADCs consist monoclonal antibody, linker, cytotoxic payload, designed to target specific antigens on tumor while minimizing collateral damage. Mechanistically, internalized via endocytosis, releasing payload within lysosome, potentially affecting neighboring cells. ADC development progressed through multiple generations, each addressing limitations its predecessors. From gemtuzumab ozogamicin trastuzumab emtansine (T-DM1), now third-generation agents such as deruxtecan (DS-8201) disitamab vedotin (RC48), improvements have been made selectivity, potency, linker stability, reduced off-target effects. Significant success seen targeting human epidermal growth factor receptor 2 trophoblast cell-surface antigen antigens, especially patients breast cancer, including those resistant previous therapies. The future includes exploring new surface bispecific antibodies, immune-activating radiopharmaceutical-loaded ADCs, masked for tissue-specific activation. Ongoing research aims optimize treatment efficacy toxicity, expanding potential combination therapy. represent promising frontier treatment, continued enhancing their beyond. This review provides comprehensive exploration ADCs' evolution offering molecular perspective inform clinical practice update colleagues this dynamic field.

Language: Английский

Amino Acids Frequency and Interaction Trends: Comprehensive Analysis of Experimentally Validated Viral Antigen–Antibody Complexes DOI

Roylan Pais,

Anil Kumar Nagraj,

Riya Patel

et al.

Molecular Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Language: Английский

Citations

1
Amino acids characterization based on frequency and interaction analysis in human antigen-antibody complexes from Thera-SAbDab DOI Creative Commons

Roylan Pais,

Anil Kumar Nagraj,

Akshata S. Gavade

et al.

Human Antibodies, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Background Antibodies are composed of light and heavy chains, both which have constant variable regions. The diversity, specific binding ability therapeutic potential antibodies determined by hypervariable loops called complementarity-determining regions (CDRs), with the other being framework Objective To investigate key amino acid patterns in various antibody human antigen-antibody (Ag-Ab) complexes collected from Thera-SAbDab database. Method study focuses on identifying frequency, diversity index CDRs, paratope-epitope interactions, bond formation types among selected Ag-Ab complexes. Results results revealed that Ser is highly distributed overall chain CDRs while Gly CDRs. CDR profiling analysis indicated average 60% to 70%, chain, it 50% 60%. Aromatic residues such as Tyr, Trp Phe top contributors these interactions chains. Moreover, we examined frequency acids chains Importantly, outcome this leverages depth single residues, dipeptides, tripeptides for Conclusion We conclude interaction centered will benefit engineering parameters design, optimization, affinity maturation, development.

Language: Английский

Citations

1
Production and characterization of novel antioxidant peptides from mulberry leaf ferment using B. subtilis H4 and B. amyloliquefaciens LFB112 DOI Creative Commons
Zaheer Abbas, Jing Zhang,

Yucui Tong

et al.

Food Chemistry, Journal Year: 2025, Volume and Issue: 482, P. 144022 - 144022

Published: April 6, 2025

The objective of this study was to isolate and characterize antioxidant peptides from mulberry leaves fermented with Bacillus subtilis H4 amyloliquefaciens LFB112. results indicated that fraction F4 (<1 kDa) exhibited superior DPPH activity compared the F1 (>10 kDa), F2 (3-10 F3 (1-3 fractions, cytoprotective effect against lipopolysaccharides (LPS)-induced oxidative stress in RAW264.7 cells. Three novel peptides, FRFDP, RFGG, GPPLAFGGGP, were identified leaf ferment, docking showed these could form stable carbon (covalent) hydrogen bonds active sites Keap1, thus regulating Keap1-Nrf2 pathway by blocking Nrf2 binding on Keap1. These significantly upregulated mRNA expression Nrf2, HO-1, NQO1, providing indirect evidence their potential enhance cellular defense via possible activation pathway. Furthermore, good ABTS scavenging activities, indicating as peptides. This offers valuable insights into integration developing ferment a functional food use feed additive.

Language: Английский

Citations

1
Isoelectric point, net charge and amino acid analysis of experimentally validated therapeutic antibodies DOI

Anil Kumar Nagraj,

Riya Patel,

Akshata S. Gavade

et al.

In Silico Pharmacology, Journal Year: 2025, Volume and Issue: 13(2)

Published: April 17, 2025

Language: Английский

Citations

0
Design and Binding Affinity of Antisense Peptides for Snake Venom Neutralization DOI Creative Commons

Ivan Biruš,

Tino Šeba, Marija Kušter Marić

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 903 - 903

Published: Feb. 15, 2025

Snakebites are a significant public health problem in many tropical and subtropical regions, causing extensive morbidity mortality. Traditional snake antivenoms face multiple challenges, including allergenicity, high production costs, logistical difficulties, highlighting the urgent need for new therapeutic approaches. This pilot study explores potential of oligopeptides as inhibitors targeting neurotoxic sites ammodytoxin A (AtxA; PDB: 3G8G) from Vipera ammodytes. We selected two sense to represent critical regions AtxA targets inhibition by complementary antisense peptides. Utilizing heuristic peptide design based on molecular recognition theory, we modeled counterparts each oligopeptide. The peptides were commercially synthesized, their binding affinities evaluated using spectrofluorometric titrations. determined dissociation constants (KD) range 1-10 μM all sense-antisense pairs, revealing relatively strong affinities. Confirmation prompted further investigation into native target protein through global docking simulations HPEPDOCK web server. results highlight applicability theory development that could change strategies various biomedical fields. Further studies needed investigate efficacy broader applications these

Language: Английский

Citations

0
Antibody-Drug Conjugates in Breast Cancer: Toward a Molecular Perspective Into Clinical Practice DOI
Roberto Paz-Manrique, Joseph A. Pinto, Guillermo Valencia

et al.

JCO Precision Oncology, Journal Year: 2024, Volume and Issue: 8

Published: Oct. 1, 2024

Antibody-drug conjugates (ADCs) are at the forefront of cancer therapy, combining targeted precision with potent cytotoxicity. Conceived by Paul Ehrlich in early 1900s, concept a magic bullet selectively eliminating cells has evolved alongside bioengineering and biology advancements. ADCs consist monoclonal antibody, linker, cytotoxic payload, designed to target specific antigens on tumor while minimizing collateral damage. Mechanistically, internalized via endocytosis, releasing payload within lysosome, potentially affecting neighboring cells. ADC development progressed through multiple generations, each addressing limitations its predecessors. From gemtuzumab ozogamicin trastuzumab emtansine (T-DM1), now third-generation agents such as deruxtecan (DS-8201) disitamab vedotin (RC48), improvements have been made selectivity, potency, linker stability, reduced off-target effects. Significant success seen targeting human epidermal growth factor receptor 2 trophoblast cell-surface antigen antigens, especially patients breast cancer, including those resistant previous therapies. The future includes exploring new surface bispecific antibodies, immune-activating radiopharmaceutical-loaded ADCs, masked for tissue-specific activation. Ongoing research aims optimize treatment efficacy toxicity, expanding potential combination therapy. represent promising frontier treatment, continued enhancing their beyond. This review provides comprehensive exploration ADCs' evolution offering molecular perspective inform clinical practice update colleagues this dynamic field.

Language: Английский

Citations

1