PLA-PEG-PLA diacrylate from PolySciTech Used in testing of crosslinked rituximab-loaded nanoparticles for treatment of non-Hodgkin’s lymphoma in novel mouse model

 

Replicating the human body conditions in another animal is not a trivial task however necessary for creating therapies against complex diseases such as cancer which can not be replicated using cell-cultures or other benchtop techniques. Recently, researchers at University of California Los Angeles and University of Alabama used PLA-PEG-PLA-diacrylate (AI102) from PolySciTech (www.polyscitech.com) to form crosslinked particles loaded with Rituximab as a cancer therapy and tested these against a novel mouse model. This research holds promise to improve both therapies and testing of those therapies for treatment of cancer. Read more: Wen, Jing, Lan Wang, Jie Ren, Emiko Kranz, Shilin Chen, Di Wu, Toshio Kanazawa, Irvin Chen, Yunfeng Lu, and Masakazu Kamata. "Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model." Journal for ImmunoTherapy of Cancer 9, no. 2 (2021): e001524. https://jitc.bmj.com/content/9/2/e001524.abstract

“Abstract: Background Despite the numerous applications of monoclonal antibodies (mAbs) in cancer therapeutics, animal models available to test the therapeutic efficacy of new mAbs are limited. NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice are one of the most highly immunodeficient strains and are universally used as a model for testing cancer-targeting mAbs. However, this strain lacks several factors necessary to fully support antibody-mediated effector functions—including antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity (CDC)—due to the absence of immune cells as well as a mutation in the Hc gene, which is needed for a functional complement system. Methods: We have developed a humanized mouse model using a novel NSG strain, NOD.Cg−Hc1Prkdcscid Il2rgtm1Wjl/SzJ (NSG−Hc1), which contains the corrected mutation in the Hc gene to support CDC in addition to other mechanisms endowed by humanization. With this model, we reevaluated the anticancer efficacies of nanoencapsulated rituximab after xenograft of the human Burkitt lymphoma cell line 2F7-BR44. Results: As expected, xenografted humanized NSG−Hc1 mice supported superior lymphoma clearance of native rituximab compared with the parental NSG strain. Nanoencapsulated rituximab with CXCL13 conjugation as a targeting ligand for lymphomas further enhanced antilymphoma activity in NSG−Hc1 mice and, more importantly, mediated antilymphoma cellular responses. Conclusions: These results indicate that NSG−Hc1 mice can serve as a feasible model for both studying antitumor treatment using cancer targeting as well as understanding induction mechanisms of antitumor cellular immune response.”