{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:07:13Z","timestamp":1772168833289,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.140284.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000}}],"reference-count":65,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>Background Conventional chemotherapy results in severe toxic side effects due to affecting normal and cancer cells. The conjugation of chemotherapy with mAb will improve the chemotherapy selectivity towards cancer cells and at the same time will potentiate immune system to detect and kill cancer cells. The aim of the study was to prepare atezolizumab-pemetrexed conjugate using two types of linkers (linker conjugated with -NH2 of lysine amino acid in the mAb). Methods This study utilizes (for the first time) the mAb atezolizumab (AtZ) to prepare a new, selective conjugate carrier for pemetrexed (PMX) by using gamma amino butyric acid (GABA) as linker for the first time in comparison to the commonly used linker polyethylene glycol (PEG) using carbodiimide (EDC) \/ N-hydroxysulfosuccinimide (Sulfo-NHS) zero length cross linker. Stepwise evaluation for PMX-linkers linkage as well as mAb conjugates was evaluated by FTIR, 1HNMR, DSC, LC-MS, gel-electrophoresis as well as the anticancer activity against lung cells A549. Results The work revealed that two molecules of GABA combined with PMX, which in turn conjugated with an average ratio of 4:1 with mAb, while one molecule of PEG combined with PMX, which in turn conjugated with mAb in the same average ratio. The IC50 for the prepared PMX-GABA-AtZ conjugate was 0.048 \u00b5M, which was much lower than PMX alone, antibody AtZ alone as well as PMX-PEG-AtZ conjugate in a dose and time dependent manner. Conclusions The potential use of such conjugate that selectively directed to the overexpressed lung cells antigen in a low dose leading to reduction of serious side effects of PMX and the cost of therapeutically AtZ mAb used.<\/ns3:p>","DOI":"10.12688\/f1000research.140284.2","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T13:10:09Z","timestamp":1710162609000},"page":"1197","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prospective effect of linkers type on the anticancer activity of pemetrexed-monoclonal antibody (atezolizumab) conjugates"],"prefix":"10.12688","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3802-9525","authenticated-orcid":false,"given":"Faten Q.","family":"Ibraheem","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5628-1479","authenticated-orcid":false,"given":"Nidhal K.","family":"Maraie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basma Talib","family":"Al-Sudani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8957-2093","authenticated-orcid":false,"given":"Ayad M.R.","family":"Raauf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e00535-e00511","DOI":"10.1002\/prp2.535","article-title":"The pharmacology and therapeutic applications of monoclonal antibodies.","volume":"7","author":"M Castelli","year":"2019","journal-title":"Pharmacol. 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We are going forward in our future research to discover more about Atezolizumab stability and specifically temprature effect. We appreciate your feedback.","URL":"https:\/\/f1000research.com\/articles\/12-1197\/v2#referee-comment-11216","order":3,"name":"referee-comment-11216","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.163486.r309198, Youlin Zeng, Hunan Normal University, Changsha, Hunan, 12 Aug 2024, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/12-1197\/v2#referee-response-309198","order":4,"name":"referee-response-309198","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}