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Use of Immunotherapy in Gynaecological and Breast Cancer
Published in Shazia Rashid, Ankur Saxena, Sabia Rashid, Latest Advances in Diagnosis and Treatment of Women-Associated Cancers, 2022
Showket Hussain, Sandeep Sisodiya, Vishakha Kasherwal, Sonam Tulsyan, Asiya Khan
LAG3 is another potent immunotherapeutic target found on the activated immune cells, especially on NK cells and T-cell lines [30]. LAG3 possesses a higher affinity than CD4 and is shown to be the probable receptor for MHC class II molecules. LAG-3 is claimed to inhibit various cellular processes like homeostasis of T cells, their proliferation and activation and is also known to contribute significantly towards the suppression behaviour of Tregs. A study on the soluble version of LAG-3 IMP321 suggested that no significant adverse events were found to be associated, and it can be used as a future treatment for breast cancer [31]. Till now, no LAG-3–based approved drugs are available in the market, but several clinical trials to ICI are ongoing.
Characterization of a novel anti-human lymphocyte activation gene 3 (LAG-3) antibody for cancer immunotherapy
Published in mAbs, 2019
Xiaojie Yu, Xiao Huang, Xiuxiu Chen, Jianfei Liu, Chenglin Wu, Qian Pu, Yuxiao Wang, Xiaoqiang Kang, Lijun Zhou
As shown on clinicaltrials.gov, numerous LAG-3-modulating agents have entered clinical trials. For example, IMP321 (Prima BioMed/Immutep) was designed as an antigen-presenting cell activator. Relatlimab (Bristol-Myers Squibb) is a human IgG4 antibody identified from a mouse-source phage library screen, while LAG525 (Novartis) and MK-4280 (Merck) are humanized antibodies. LBL-007 is a novel anti-LAG-3 antibody obtained from a large human phage library. It showed good binding specificity and stable metabolic parameters in monkeys. In this study, LBL-007 showed better uptake into cells than relatlimab analog, suggesting that LBL-007 may have broader applications. Also, it should be noted that relatlimab analog was prepared in house. In view of different expression system or preparation processes, it cannot be inferred the performance of relatlimab analog is identical to the originator’s relatlimab.
Building on the anti-PD1/PD-L1 backbone: combination immunotherapy for cancer
Published in Expert Opinion on Investigational Drugs, 2019
Alvaro H Ingles Garces, Lewis Au, Robert Mason, Jennifer Thomas, James Larkin
IMP321 (developed by Immutep) is a soluble LAG3-Fc fusion protein that has shown clinical activity and safety in phase I trials in renal-cell, breast, and pancreatic cancers [14,25–27]. A phase I study with 21 renal-cell cancer patients who were treated with at least three doses of IMP321 had no clinically significant local or systemic AEs related to the therapy (only grade 1 local reactions). It was not observed objective tumor response but tumor growth was reduced in the higher dose group. PFS was significantly better in those patients receiving higher doses and 7 of 8 evaluable patients had SD at 3 (P = 0.015) [26]. Another phase I/II study with metastatic breast cancer patients which evaluated the combination of IMP321 with weekly paclitaxel, also showed no clinically significant local or systemic IMP321-related AEs. With the combination, grade 3 AEs reported were: asthenia, neuropathy, allergic reaction, and neutropenia. Clinical benefit was observed in 90% of patients in this trial [27].
LAG-3 antagonists by cancer treatment: a patent review
Published in Expert Opinion on Therapeutic Patents, 2019
Martin Perez-Santos, Maricruz Anaya-Ruiz, Jorge Cebada, Cindy Bandala, Gerardo Landeta, Patricia Martínez-Morales, Nemesio Villa-Ruano
Another patent submitted by Immutep (EP2205257B1 [38]), Triebel disclosed a recombinant soluble human LAG-3lg fusion protein (IMP321) that elicits a monocyte-mediated immune response. This protein has the potential for use as an anti-cancer medicament. Metastatic breast patients were administered with one subcutaneous IMP321 dose of 0.25 mg 1–2 days after chemotherapy every other week, for 24 weeks, separated by 14-day administration-free intervals. An increase of 2.5 and 3.5 in the monocyte counts in PBMC samples was observed at three and six months of treatment with IMP231, respectively. On the other hand, metastatic renal clear-cell carcinoma patients using high IMP321 dose were administered with one subcutaneous IMP321 dose of 6.25 mg every other week, for 12 weeks, separated by 14-day administration-free intervals. An increase of 2 and 3 in the monocyte counts in PBMC samples was observed at three months of treatment.