Anti-Human IL-23A (p19) (Risankizumab) [Clone ABBV-066]

Research-grade Risankizumab biosimilars are used as calibration standards or reference controls in pharmacokinetic (PK) bridging ELISAs to generate standard curves against which unknown serum samples are quantified, thereby enabling accurate measurement of risankizumab concentrations in clinical or preclinical PK studies.

Research context and method:

• In a PK bridging ELISA, known concentrations of reference-grade risankizumab (often biosimilar or research-grade material when originator drug is not available) are spiked into drug-naive serum to construct a standard calibration curve. This curve translates absorbance (or other signal) to actual drug concentration, forming the basis for quantifying drug levels in unknown clinical samples.
• Validation studies demonstrate that if the research-grade biosimilar and reference (originator) product behave similarly in the assay (bioanalytical equivalence), then either may be used as the analytical standard. Best practice is to establish that the assay measures both the biosimilar and reference product with equivalent sensitivity, precision, and accuracy before relying on the biosimilar as the sole calibrator.
• Quality control (QC) samples prepared from both the reference and biosimilar are assayed alongside clinical samples to validate precision and accuracy across runs.
• The PK bridging ELISA typically uses an antigen-capture format (e.g., sandwich or bridging ELISA) where the standard (biosimilar risankizumab) is captured and detected using reagents specific to risankizumab, ensuring that assay quantification is relevant to both biosimilar and originator molecules if they are analytically equivalent.

Key details of implementation:

• Standard curve preparation: Serial dilutions of the biosimilar risankizumab are made in drug-free human serum to a range of concentrations encompassing expected clinical levels, as recommended by method validation studies (e.g., 50–12,800 ng/mL).
• Assay usage: Unknown serum samples from PK studies are run in parallel with the standards, allowing for direct interpolation of drug concentration against the biosimilar standard curve.
• Bioanalytical comparability: Prior to using a biosimilar as a single universal standard, method qualification and validation include parallelism, accuracy, and precision assessments using both biosimilar and reference standard preparations to ensure no matrix or molecule-specific bias. Only if criteria for equivalence (e.g., 90% confidence intervals within predefined equivalence limits) are met is the biosimilar used exclusively as the assay standard.
• Purpose: This approach standardizes measurement, reduces variability associated with multiple standards, and supports regulatory requirements for robust demonstration of PK similarity in biosimilar development programs.

In summary, research-grade risankizumab biosimilars are critical tools for PK bridging ELISA calibration, provided their analytical performance in the assay is duly validated against the originator/reference comparator, ensuring accurate and reliable PK data for biosimilar development or routine drug monitoring.

The primary models where a research-grade anti-IL-23A (p19) antibody is administered in vivo to study tumor growth inhibition and to characterize tumor-infiltrating lymphocytes (TILs) are murine syngeneic tumor models, such as B16F10 melanoma and EG7 (EL4-OVA) thymoma. Humanized mouse models may also be relevant, but documented in vivo studies of anti-IL-23A with detailed TIL characterization are mainly in syngeneic settings.

Key details:

• B16F10 melanoma model (syngeneic, C57BL/6 mice):

  • Widely used to test immunotherapies including anti-IL-23 antibodies.
  • Administration of anti-IL-23 (p19) antibody, typically a neutralizing monoclonal antibody, inhibits metastasis and subcutaneous tumor growth.
  • Characterization of TILs (NK, CD8+, CD4+ T cells) is feasible; NK cell depletion abrogates the antibody effect on metastases, and analysis has been performed by flow cytometry and single-cell RNA-seq.
  • B16F10 is known for low baseline immune infiltration; thus, it allows the study of immunotherapy-induced changes.

• EG7 (EL4-OVA) thymoma (syngeneic, C57BL/6 mice):

  • Used to interrogate roles of adaptive immunity following IL-23A blockade.
  • Anti-IL-23A antibody promotes adaptive (T cell-mediated) antitumor immunity in this setting, as measured by tumor growth inhibition and functional TIL analysis.

• Other syngeneic models such as RENCA (renal carcinoma, BALB/c mice) and CT26 (colon carcinoma, BALB/c mice) are well characterized for immune composition and responses to immunotherapies, but direct published use with anti-IL-23A (p19) antibodies for TIL characterization is less frequently reported; these models, however, are suitable for such studies.

• Humanized mouse models (immunodeficient mice engrafted with human immune cells and/or tumors) are essential for testing fully human or humanized anti-IL-23A antibodies, but direct evidence from the search results about TIL profiling with anti-IL-23A in such models is lacking. Nonetheless, novel high-affinity humanized anti-IL-23 antibodies (e.g., BI 655066) have been generated and characterized for in vivo use, supporting the feasibility of such studies.

Summary Table: Experimental Models for Anti-IL-23A (p19) Antibody In Vivo Studies

Conclusion:
Mouse syngeneic tumor models, particularly B16F10 melanoma and EG7, represent the primary systems for in vivo administration of anti-IL-23A (p19) antibodies to study tumor growth inhibition and TILs. Humanized models are technically feasible for human antibodies, but published in vivo TIL studies are sparse.

Researchers have not yet directly assessed the use of Risankizumab biosimilars in combination with other checkpoint inhibitors (such as anti-CTLA-4 or anti-LAG-3 biosimilars) for synergy in complex immune-oncology models, according to currently available published studies.

Some essential points for context and supporting details:

• Risankizumab is an IL-23 inhibitor, primarily used for treating conditions like psoriasis and Crohn’s disease. It acts by targeting the p19 subunit of IL-23, affecting the Th17 pathway, which is distinct from classic immune checkpoint pathways such as PD-1/PD-L1 or CTLA-4.
• Checkpoint inhibitor combinations (e.g., anti-CTLA-4 plus anti-PD-1/PD-L1) are already widely studied in immune-oncology to increase anti-tumor efficacy through complementary immune mechanisms. These studies show that combinations can provide additive or synergistic effects by enhancing T cell responses via different mechanisms. However, Risankizumab (and other IL-23 inhibitors) are not classic checkpoint inhibitors, and their combined use with true checkpoint blockers in oncology models is not well reported.
• The predominant research focus for Risankizumab's combinations has been with immunosuppressive agents in autoimmune diseases such as Crohn’s disease or psoriasis—not in oncology or combination with checkpoint blockade.
• A recent clinical case report described the use of Risankizumab to manage psoriasis induced by checkpoint inhibitor therapy (nivolumab), not to treat cancer synergistically. This context demonstrated that Risankizumab might be safely administered in patients receiving immune checkpoint inhibitors for cancer, but not as part of a combined anticancer immunotherapy approach.

Gaps and inferences:

• There is no current evidence that researchers are systematically testing Risankizumab biosimilars in combination with checkpoint inhibitors for synergistic anti-tumor effects in preclinical or clinical immune-oncology models.
• The idea of combining agents with non-overlapping mechanisms (such as IL-23 axis inhibition and checkpoint inhibition) could be theoretically interesting for modulating the immune system, especially for managing side effects or for certain tumor microenvironment subtypes, but supporting publications are lacking.
• The literature reinforces that further research would be needed to clarify whether IL-23 inhibition could affect checkpoint inhibitor response rates or toxicity in oncology.

In summary, while combinations of immune checkpoint inhibitors themselves (e.g., anti-CTLA-4 and anti-PD-1) are actively investigated and provide evidence of synergy, the use of Risankizumab biosimilars with checkpoint inhibitors for synergistic oncology effects has not yet been systematically studied or reported in the literature.

A Risankizumab biosimilar can be used as either the capture or detection reagent in a bridging ADA (anti-drug antibody) ELISA to monitor a patient's immune response against Risankizumab by providing an antigen source that interacts specifically with circulating ADAs in patient serum, enabling quantification of immunogenicity.

Bridging ADA ELISA principle:

• The assay detects patient-generated antibodies (ADAs) against the therapeutic drug.
• The ELISA plate is coated with Risankizumab (or its biosimilar) as the capture reagent.
• Patient serum is added; if ADAs are present, they will bind Risankizumab.
• A labeled version of Risankizumab biosimilar (biotinylated, digoxigenin-tagged, etc.) serves as the detection reagent, binding to the other free arm of the ADA, forming a "bridge."
• Signal generation (often via HRP, chemiluminescence, etc.) reveals the presence and quantity of ADA.

Role of the biosimilar:

• Using a biosimilar as both capture and detection reagent ensures assay supply stability, reduces cost, and risks of overusing the originator molecule.
• The biosimilar must be analytically comparable and display high structural similarity to originator Risankizumab, ensuring it presents the same immunological epitopes necessary for ADA detection.
• In validated assays with adalimumab, analogous biosimilar reagents (purified in-house or commercially sourced) have been used as both capture and detection molecules, ensuring clinical relevance and sensitivity.

Importance for immunogenicity monitoring:

• Detecting ADAs is critical for evaluating immune responses and potential therapeutic failure or adverse effects during biosimilar or originator treatment.
• Proper selection and validation of the biosimilar as a reagent increases assay sensitivity and specificity, aligning with rigorous standards (such as those outlined for adalimumab ADA ELISA).

In summary, Risankizumab biosimilar is used in bridging ELISA as both the capture and detection reagent to form a sandwich with the patient's ADA, facilitating reliable and sensitive monitoring of immune responses against therapy. The approach follows established bioanalytical validation practices to ensure clinical utility.