huPD-1/hPD-L1/huCD19 Mouse

Programmed cell death protein 1 (PDCD1/PD-1) is a member of the B7-CD28 family of costimulatory receptor proteins. It is expressed on activated T cells and functions as an immunosuppressive receptor involved in regulating the function of effector T cells, including CD8⁺ T cells, and promoting the differentiation of CD4⁺ T cells into regulatory T cells. PD-1 is expressed in various tumors and plays an important role in antitumor immunity. In addition, PD-1 is involved in immune tolerance and suppresses antitumor and antimicrobial immune responses ^[1].

PDL1, also known as programmed cell death 1 ligand 1 (PD-L1), cluster of differentiation 274 (CD274), or B7 homolog 1 (B7-H1), encodes an immunosuppressive receptor ligand mainly expressed by hematopoietic and non-hematopoietic cells, including T cells, B cells, and various tumor cells ^[2]. PD-L1 is a type I transmembrane protein containing immunoglobulin V-like (IgV) and C-like (IgC) domains. PD-L1 interacts with the PD-1 receptor expressed on T cells, thereby inhibiting T cell activation and effector function. This interaction prevents excessive immune responses against normal tissues but can also be exploited by tumor cells to evade immune surveillance. Monoclonal antibodies targeting PD-L1 can disrupt the interaction between PD-1 and PD-L1, reverse PD-1/PD-L1-mediated immune suppression, reactivate T cells, and initiate antitumor immune responses ^[3].

The CD19 gene encodes a member of the immunoglobulin superfamily and serves as a key co-receptor in the B cell receptor (BCR) signaling pathway, playing an essential role in B cell development, activation, and differentiation. CD19 is a pan-B cell marker that is specifically expressed in the B cell lineage and remains stably expressed throughout B cell development, from pre-B cells to mature B cells and memory B cells. CD19 acts as a positive regulator of BCR signaling. The CD19 protein forms a B cell-specific signaling complex with CD21 (complement receptor type 2), CD81 (tetraspanin), and CD225 (Leu13), which lowers the threshold for antigen-induced B cell activation ^[4].

The huPD-1/hPD-L1/huCD19 mouse is a triple-gene humanized model generated by crossing the hPDL1-V(2) mouse (Catalog No.: C001235), the huPD-1 mouse (Catalog No.: C001524), and the huCD19 mouse (Catalog No.: C001731). This model can be used for pharmacodynamic evaluation, mechanism of action studies, and combination therapeutic strategy development of anti-CD19 therapeutics and PD-1/PD-L1 immune checkpoint inhibitors. It supports the evaluation of combination therapies involving anti-CD19 CAR-T cells, bispecific antibodies, and immune checkpoint inhibitors, as well as studies of B cell–T cell interactions and tumor immune microenvironment mechanisms. This model provides a preclinical research platform for developing innovative immunotherapies for B-cell malignancies, including acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL).