In recent studies, we established and validated two new human lymphoma cell‑line–derived xenograft (CDX) models, generated from the OCI‑Ly19 (diffuse large B‑cell lymphoma, DLBCL) and REC‑1 (mantle cell lymphoma) cell lines. These models were developed in strategic collaboration with BIMINI Biotech, an innovative start-up advancing first-in-class therapies for oncology and autoimmune disease, as part of a Eurostars grant–funded project.

Within this collaboration, the CDX models were applied to explore therapeutic strategies targeting the Wiskott–Aldrich syndrome protein (WASP) — a key regulator of actin filament reorganization, WASP is crucial for efficient actin polymerization. WASP has critical functional roles in lymphoid and myeloid cell proliferation, migration, receptor signaling, cytotoxicity, and phagocytosis. The protein has demonstrated both tumor‑suppressive and oncogenic functions in hematologic malignancies, providing a strong rationale for its therapeutic evaluation.

From target validation to CDX: A flexible and translational preclinical workflow

Translating early discovery findings into robust in vivo evaluation requires an integrated and adaptive approach. In collaboration with BIMINI, InnoSer developed a translational workflow spanning:

• In vitro screening and target validation;
• Selection of relevant lymphoma cell lines based on WASp biology;
• Generation of tailored CDX models;
• Execution of in vivo efficacy studies;
• Toxicology assessments.

This cohesive platform ensures scientific continuity, efficient decision making, and consistent data quality across development stages.

Throughout the collaboration, the direct and flexible working relationship enabled joint strategic guidance in selecting the most appropriate lymphoma models. Regular milestone discussions ensured alignment, adaptability, and efficient progression from in vitro validation to successful CDX establishment.

Strengthening our lymphoma portfolio with newly validated CDX models

For BIMINI’s targeted therapeutic strategy, the REC‑1 and OCI‑Ly19 models were selected based on WASp expression and complementary biological behavior. The REC-1 and OCI-Ly19 CDX models represent biologically distinct B-cell lymphoma subtypes, REC-1 carrying the hallmark t(11;14)(q13;q32) translocation, whereas OCI-Ly19 harbors the canonical t(14;18)(q32;q21) IGH–BCL2 rearrangement.

Importantly for this study, these CDX models have reported differences in their responsiveness to BTK inhibition, with REC‑1 described as ibrutinib‑sensitive, whereas OCI‑Ly19 shows reduced sensitivity or resistance. This differential pharmacological profile makes the pair highly suitable for downstream efficacy evaluation across both BTK inhibitor–responsive and –non‑responsive lymphoma settings.

Following subcutaneous implantation in NOD/SCID mice, both CDX models demonstrated robust and reproducible tumor growth kinetics, making them suitable for evaluating monotherapies, combination regimens, antibody–drug conjugates (ADCs), and small‑molecule inhibitors (Figure 1).

FIGURE 1. Tumor growth curve validation data from the two new human lymphoma cell line–derived (CDX) mouse models. Following in vitro expansion, human lymphoma cells from the A) REC-1 and B) OCI-Ly19 cell lines were injected subcutaneously into the left (single-flank) or both left and right (bilateral) flanks of NOD/SCID mice at varying cell densities. Data are presented as mean tumor volume ± standard error of the mean (SEM), with n = 3 mice per group for single-flank injections and n = 6 mice per group for bilateral-flank injections.

Evaluating therapeutic response in REC‑1 and OCI‑Ly19 lymphoma CDX models

With both CDX models successfully established and validated, we advanced to assess their response to BTK inhibition. PBS was used as the negative control, and ibrutinib—a small‑molecule inhibitor of Bruton’s tyrosine kinase (BTK) that suppresses B‑cell proliferation—serving as the positive control.

In line with literature‑reported profiles, REC‑1 showed clear growth inhibition under ibrutinib, confirming its suitability as a BTK‑responsive reference model. In contrast, OCI‑Ly19 did not display reduced tumor progression under identical treatment conditions, reflecting its reduced sensitivity to BTK inhibition and offering a complementary, non‑responsive lymphoma setting for therapeutic evaluation (Figure 2).

FIGURE 2. Antitumor efficacy assessment in two human lymphoma cell line–derived (CDX) mouse models. Following CDX model development and validation, both a negative control (PBS) and a positive control (ibrutinib) were used to evaluate treatment efficacy in the A) REC-1 and B) OCI-Ly19 CDX models. Data are presented as mean tumor volume ± standard error of the mean (SEM), with n = 8 mice per group.

Reach out to our expert scientific team to learn more about our oncology models, including a wide range of cancer cell lines and CDX mouse model options. Our team will work together with you to identify the most suitable model, taking into account your needs and your therapeutics’ MoA.