Anti-Human CD319 (SLAMF7) (Elotuzumab)

Research-grade Elotuzumab biosimilars are used in pharmacokinetic (PK) bridging ELISA assays as calibration standards (for generating a quantitative standard curve) or as reference controls for assay validation and bridging studies. Their primary roles are to provide an analytically consistent, non-clinical version of the drug antibody to enable precise measurement of Elotuzumab concentrations in serum samples from PK studies.

Key points on their use:

• Calibration Standards:

  • A research-grade Elotuzumab biosimilar with equivalent binding/structural characteristics to the therapeutic antibody is serially diluted in a relevant biological matrix (typically human serum or buffer), spanning the expected concentration range found in test samples.
  • These spiked standards are added to each ELISA plate alongside test samples. They are used to generate a standard curve of signal (optical density) versus concentration, which is crucial for converting raw assay signals from patient or animal serum into quantifiable drug concentration values.
  • The biosimilar is specifically chosen to closely match the originator drug's epitopes and behavior in the assay, ensuring that the ELISA platform is sensitive and specific for both the original and biosimilar forms.

• Reference Controls:

  • Biosimilars can also act as positive controls to verify that the assay can accurately detect known concentrations, helping monitor assay performance, reproducibility, and detect any shifts in sensitivity or specificity over time.
  • Reference controls are typically run at low, medium, and high concentrations to assess the precision and accuracy of both intra-assay and inter-assay measurements.

• Bridging ELISA Specifics:

  • In a PK bridging ELISA, an anti-idiotypic capture antibody specific for Elotuzumab’s unique variable region is immobilized on the plate. The serum sample (containing Elotuzumab) and the biosimilar calibration standard compete for binding.
  • Detection is typically performed using an anti-idiotypic detection antibody conjugated to an enzyme (e.g., HRP), as described in bridging formats for other monoclonal antibodies.
  • The output standard curve allows accurate interpolation of Elotuzumab concentrations in unknown samples.

Example Workflow:

• Prepare a serial dilution of research-grade Elotuzumab biosimilar in pooled human serum or assay buffer (e.g., 0.5 ng/mL to 200 ng/mL).
• Add calibration standards, test serum samples, and reference controls to a 96-well ELISA plate pre-coated with anti-idiotypic antibody.
• Incubate, wash, and add detection antibody (HRP-conjugated; anti-idiotypic or anti-human Fc).
• Develop with a suitable substrate, measure absorbance, and use the standard curve to calculate sample concentrations.
• Reference biosimilars ensure the system detects authentic Elotuzumab or equivalent drug regardless of source (branded vs. biosimilar) and allow for comparability/bioequivalence trials.

Summary Table:

References:

• Example workflow with Trastuzumab ELISA kit for biosimilar quantification.
• Use of biosimilar and originator antibodies as calibrators and controls in PK ELISA validation.
• Research-grade Elotuzumab biosimilars with matching variable regions are suitable as reference standards.
• Bridging ELISA schematic and explanation of biosimilars as reference/control in PK ELISAs.

If you require the specifics of buffer composition, dilution schemes, or plate formats, these are detailed in kit instructions or primary assay validation reports which should be consulted for regulatory submission.

Currently, there is no specific information available in the search results about the administration of a research-grade anti-CD319 antibody in syngeneic or humanized models to study tumor growth inhibition and characterize tumor-infiltrating lymphocytes (TILs). However, we can discuss the types of models that are commonly used for such studies and how they might be relevant.

Syngeneic Models

• Definition: Syngeneic tumor models involve using genetically identical mice with implanted tumors derived from the same strain. These models are widely used in preclinical studies because they retain a fully functional immune system, making them ideal for evaluating immunotherapeutic agents.
• Application: Syngeneic models could potentially be used to study the effects of anti-CD319 antibodies by evaluating their impact on tumor growth and TILs. However, specific data on anti-CD319 antibodies in these models is not provided in the search results.

Humanized Models

• Definition: Humanized models typically involve mice with human immune systems (e.g., NSG-Tg(Hu-IL15) transgenic mice) and are used to study human immune responses more accurately.
• Application: While humanized models are crucial for studying human-specific immune interactions, the search results do not mention the use of anti-CD319 antibodies in these models specifically for studying TILs and tumor growth inhibition.

Relevant Findings

• CD319 (SLAMF7): Recent studies have shown that CD319 (SLAMF7) can play roles in immune cell interactions, potentially influencing tumor environments.
• ABV-319: Although not directly relevant to CD319, ABBV-319 is a CD19-targeting therapy that demonstrates potent antitumor effects in B-cell malignancies, showing how targeted therapies can be effective in specific models.

For studying tumor growth inhibition and characterizing TILs with an anti-CD319 antibody, researchers might consider using syngeneic models for their intact immune systems or humanized models to study human-specific immune responses. However, specific data on anti-CD319 antibodies in these contexts is not available in the provided search results.

Researchers use Elotuzumab biosimilars in conjunction with other checkpoint inhibitors such as anti-CTLA-4 or anti-LAG-3 biosimilars in complex immuno-oncology models primarily to investigate potential synergistic effects on immune-mediated tumor destruction and to overcome resistance seen with single-agent therapies.

Essential context and supporting details:

• Elotuzumab Mechanism and Model Use:
  Elotuzumab biosimilars target SLAMF7 on natural killer (NK) cells and myeloma cells, activating NK cytotoxicity and flagging tumor cells for immune destruction. These biosimilars are designed for research use, mirroring the clinically approved monoclonal antibody but are more cost-effective and widely accessible for preclinical experimentation.

• Combination Rationale:
  Combinations with checkpoint inhibitors—such as anti-CTLA-4 or anti-LAG-3—are of interest because each inhibitor modulates distinct but complementary immune pathways. For example:

  • Anti-CTLA-4 predominantly enhances T-cell activation in lymph nodes.
  • Anti-LAG-3 works at the tumor site and can coordinate with PD-1/PD-L1 pathways to boost local immune responses.

  By combining these with Elotuzumab, which chiefly activates NK cells and engages antibody-dependent cellular cytotoxicity (ADCC), researchers seek to induce broader and deeper anti-tumor immunity than is seen with monotherapies.

• Implementation in Models:
  In complex immune-oncology models—such as humanized mouse models or sophisticated in vitro co-culture systems—researchers:

  • Administer Elotuzumab biosimilar antibodies alongside checkpoint inhibitor biosimilars.
  • Assess synergistic enhancement of immune cell activity (e.g., increased T cell proliferation, greater NK cell cytotoxicity, and heightened cytokine/chemokine release).
  • Analyze the effect on tumor regression, immune phenotype modulation, and potential reduction of immunosuppressive barriers.
  • Elotuzumab biosimilars are ideal for such research because they provide reproducibility and lower experimental costs versus clinical-grade antibodies.

• Research Applications—Synergistic Effects:
  Preclinical studies have shown that combining Elotuzumab with other ICIs can:

  • Enhance NK and T-cell activity,
  • Promote more robust and durable anti-tumor effects,
  • Potentially overcome resistance observed during single-agent treatments.

  For example, combining Elotuzumab (SLAMF7 targeting) with thalidomide derivatives increased NK activation and anti-tumor activity in preclinical models, illustrating the potential for synergy when integrating additional ICIs.

• Experimental Evaluations:
  Synergy is often quantified by:

  • Tumor growth delay/regression in animal models,
  • Immune infiltrate profiling via flow cytometry or multiparameter imaging,
  • Functional assays for cytotoxicity, cytokine production, and T/NK cell activation markers.

Additional information:

• No routinely published studies were found specifically involving Elotuzumab biosimilars with anti-LAG-3 or anti-CTLA-4 biosimilars together; however, this synergistic multi-agent approach is strongly supported by mechanistic and early combination data from diverse checkpoint inhibitor pairings.
• The main barrier for such studies remains cost and access to multiple high-quality biosimilars—issues which the research-use-only biosimilars aim to overcome.

In summary, combining Elotuzumab biosimilars with other checkpoint inhibitor biosimilars in complex immuno-oncology models serves to dissect synergy between innate (NK cell–mediated) and adaptive (T cell–mediated) immune responses, revealing strategies to augment anti-cancer immunity and address resistance mechanisms in preclinical investigation.

A Elotuzumab biosimilar is commonly used as either the capture reagent or the detection reagent in a bridging ADA (anti-drug antibody) ELISA to monitor a patient’s immune response against elotuzumab therapy. The biosimilar antibody provides the same antigenic epitopes as the therapeutic, allowing detection of ADAs that may develop against the original drug.

In the bridging ADA ELISA:

• Capture role: The biosimilar elotuzumab is immobilized on the ELISA plate, capturing ADAs from a patient's serum that specifically bind to elotuzumab's epitopes.
• Detection role: A labeled (e.g., HRP- or biotin-tagged) biosimilar elotuzumab is added, which binds to the other arm (Fab) of the ADA, forming a "bridge"—the ADA is sandwiched between two molecules of the biosimilar drug.

This format leverages the bivalent nature of ADAs (they typically bind two drug molecules), enabling highly sensitive and specific measurement of immune responses against the therapeutic antibody. Using a biosimilar for both capture and detection ensures the recognized epitopes are identical to those of the original elotuzumab drug, improving the accuracy of ADA detection and mitigating lot-to-lot variability seen with clinical material.

Key steps:

• Coat plate: With biosimilar elotuzumab for ADA capture.
• Incubate sample: Patient serum containing potential ADAs.
• Add labeled biosimilar: To detect bridged ADAs.
• Readout: Via colorimetric or chemiluminescent signal proportional to ADA amount.

This method is widely used for immunogenicity testing of biosimilars and monoclonal antibodies and is adaptable to different drug targets and labeling strategies.

If you need precise concentrations, validation controls, or protocol variants, typical references include streptavidin-coated plates, biotin/HRP-labeling kits, and standardized readout methods depending on study needs.