Published January 30, 2015
| Version v1
Publication
Open
Chemokine Receptor-Specific Antibodies in Cancer Immunotherapy: Achievements and Challenges
Creators
- 1. Centro Nacional de Biotecnología
- 2. Consejo Superior de Investigaciones Científicas
- 3. Fundación para la Investigación, Docencia y Prevención del Cáncer
- 4. Centro de Investigaciones Biológicas Margarita Salas
Description
The 1990s brought a burst of information regarding the structure, expression pattern, and role in leukocyte migration and adhesion of chemokines and their receptors. At that time, the FDA approved the first therapeutic antibodies for cancer treatment. A few years later, it was reported that the chemokine receptors CXCR4 and CCR7 were involved on directing metastases to liver, lung, bone marrow, or lymph nodes, and the over-expression of CCR4, CCR6, and CCR9 by certain tumors. The possibility of inhibiting the interaction of chemokine receptors present on the surface of tumor cells with their ligands emerged as a new therapeutic approach. Therefore, many research groups and companies began to develop small molecule antagonists and specific antibodies, aiming to neutralize signaling from these receptors. Despite great expectations, so far, only one anti-chemokine receptor antibody has been approved for its clinical use, mogamulizumab, an anti-CCR4 antibody, granted in Japan to treat refractory adult T-cell leukemia and lymphoma. Here, we review the main achievements obtained with anti-chemokine receptor antibodies for cancer immunotherapy, including discovery and clinical studies, proposed mechanisms of action, and therapeutic applications.
Translated Descriptions
⚠️
This is an automatic machine translation with an accuracy of 90-95%
Translated Description (Arabic)
جلبت التسعينيات موجة من المعلومات المتعلقة بالبنية ونمط التعبير والدور في هجرة الكريات البيض والتصاق الكيموكينات ومستقبلاتها. في ذلك الوقت، وافقت إدارة الغذاء والدواء على أول أجسام مضادة علاجية لعلاج السرطان. بعد بضع سنوات، أفيد أن مستقبلات الكيموكين CXCR4 و CCR7 كانت متورطة في توجيه النقائل إلى الكبد أو الرئة أو نخاع العظام أو الغدد الليمفاوية، والإفراط في التعبير عن CCR4 و CCR6 و CCR9 من قبل بعض الأورام. ظهرت إمكانية تثبيط تفاعل مستقبلات الكيموكين الموجودة على سطح الخلايا السرطانية مع روابطها كنهج علاجي جديد. لذلك، بدأت العديد من المجموعات والشركات البحثية في تطوير مضادات جزيئات صغيرة وأجسام مضادة محددة، بهدف تحييد الإشارات من هذه المستقبلات. على الرغم من التوقعات الكبيرة، حتى الآن، لم تتم الموافقة إلا على جسم مضاد واحد لمستقبلات الكيموكين لاستخدامه السريري، وهو موغاموليزوماب، وهو جسم مضاد لـ CCR4، تم منحه في اليابان لعلاج سرطان الدم التائي وسرطان الغدد الليمفاوية للبالغين. هنا، نستعرض الإنجازات الرئيسية التي تم الحصول عليها مع الأجسام المضادة لمستقبلات الكيموكين للعلاج المناعي للسرطان، بما في ذلك الاكتشاف والدراسات السريرية، وآليات العمل المقترحة، والتطبيقات العلاجية.Translated Description (French)
Les années 1990 ont apporté une explosion d'informations concernant la structure, le modèle d'expression et le rôle dans la migration et l'adhésion des leucocytes des chimiokines et de leurs récepteurs. À cette époque, la FDA a approuvé les premiers anticorps thérapeutiques pour le traitement du cancer. Quelques années plus tard, il a été rapporté que les récepteurs de chimiokines CXCR4 et CCR7 étaient impliqués dans l'orientation des métastases vers le foie, le poumon, la moelle osseuse ou les ganglions lymphatiques, et la surexpression de CCR4, CCR6 et CCR9 par certaines tumeurs. La possibilité d'inhiber l'interaction des récepteurs des chimiokines présents à la surface des cellules tumorales avec leurs ligands est apparue comme une nouvelle approche thérapeutique. Par conséquent, de nombreux groupes de recherche et entreprises ont commencé à développer des antagonistes de petites molécules et des anticorps spécifiques, visant à neutraliser la signalisation de ces récepteurs. Malgré de grandes attentes, jusqu'à présent, un seul anticorps anti-récepteur des chimiokines a été approuvé pour son utilisation clinique, le mogamulizumab, un anticorps anti-CCR4, accordé au Japon pour traiter la leucémie et le lymphome à cellules T réfractaires chez l'adulte. Ici, nous passons en revue les principales réalisations obtenues avec les anticorps anti-récepteurs des chimiokines pour l'immunothérapie du cancer, y compris la découverte et les études cliniques, les mécanismes d'action proposés et les applications thérapeutiques.Translated Description (Spanish)
La década de 1990 trajo una explosión de información sobre la estructura, el patrón de expresión y el papel en la migración de leucocitos y la adhesión de quimiocinas y sus receptores. En ese momento, la FDA aprobó los primeros anticuerpos terapéuticos para el tratamiento del cáncer. Unos años más tarde, se informó que los receptores de quimiocinas CXCR4 y CCR7 estaban involucrados en la dirección de metástasis al hígado, pulmón, médula ósea o ganglios linfáticos, y la sobreexpresión de CCR4, CCR6 y CCR9 por ciertos tumores. La posibilidad de inhibir la interacción de los receptores de quimiocinas presentes en la superficie de las células tumorales con sus ligandos surgió como un nuevo enfoque terapéutico. Por lo tanto, muchos grupos de investigación y empresas comenzaron a desarrollar antagonistas de moléculas pequeñas y anticuerpos específicos, con el objetivo de neutralizar la señalización de estos receptores. A pesar de las grandes expectativas, hasta ahora, solo se ha aprobado un anticuerpo anti-receptor de quimiocinas para su uso clínico, mogamulizumab, un anticuerpo anti-CCR4, otorgado en Japón para tratar la leucemia y el linfoma de células T adultas refractarias. Aquí, revisamos los principales logros obtenidos con los anticuerpos anti-receptores de quimiocinas para la inmunoterapia del cáncer, incluidos los estudios clínicos y de descubrimiento, los mecanismos de acción propuestos y las aplicaciones terapéuticas.Files
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Additional details
Additional titles
- Translated title (Arabic)
- الأجسام المضادة الخاصة بمستقبلات الكيموكين في العلاج المناعي للسرطان: الإنجازات والتحديات
- Translated title (French)
- Anticorps spécifiques aux récepteurs des chimiokines dans l'immunothérapie du cancer : réalisations et défis
- Translated title (Spanish)
- Anticuerpos específicos contra el receptor de quimiocinas en la inmunoterapia contra el cáncer: logros y desafíos
Identifiers
- Other
- https://openalex.org/W2028166635
- DOI
- 10.3389/fimmu.2015.00012
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