Anti-Human CD38 (Clone OKT10) – Purified in vivo GOLD™ Functional Grade

Clone OKT10, a mouse monoclonal antibody targeting human CD38, is primarily utilized in preclinical cancer research involving mouse models with human tumor xenografts. The antibody serves as a crucial targeting vehicle for delivering therapeutic agents to CD38-expressing tumors.

Pretargeted Radioimmunotherapy

The most prominent in vivo application involves pretargeted radioimmunotherapy (PRIT) for multiple myeloma xenografts in immunodeficient mice. This sophisticated approach enables precise delivery of radionuclides to CD38-expressing tumors, resulting in potent anti-tumor effects. In PRIT studies, OKT10 is administered first to bind tumor cells, followed by clearing agents and radiolabeled compounds that link to the pretargeted antibody.

Studies using OKT10-streptavidin chemical conjugates (OKT10-CC) demonstrated remarkable therapeutic efficacy. In mice bearing L363 myeloma xenografts, treatment with OKT10-CC followed by yttrium-90 labeled biotin achieved 100% complete remissions at the highest dose (1200µCi) by day 17, with 70% of animals remaining alive and tumor-free after 100 days. The pretargeting approach achieved tumor-to-normal organ radioactivity ratios of 10:1 for lung, 8:1 for liver, and 6:1 for kidney, demonstrating superior tumor selectivity compared to conventional directly radiolabeled antibodies.

Alpha-Particle Radioimmunotherapy

OKT10 has also been employed in alpha-emitter radioimmunotherapy using astatine-211 for disseminated multiple myeloma models. In studies with OPM-2 xenografts, treatment with ^211^At-CD38 at 45 µCi eliminated detectable disease in 100% of mice by day 41, with sustained responses through day 150. This approach proved effective across multiple myeloma cell lines including MOLP-8, OPM-2, and NCI-H929, with survival benefits that were both dose-dependent and statistically significant compared to control treatments.

These in vivo applications leverage OKT10's specificity for human CD38 to study targeted cancer therapies in preclinical models, providing valuable data for translating radioimmunotherapy approaches to clinical settings.

Based on the literature, HB2 (anti-CD7) is the most commonly used antibody in combination with OKT10 (anti-CD38), particularly in studies involving immunotoxin-based therapies targeting leukemia cells.

HB2 in Combination Therapies

HB2 and OKT10 have been extensively studied together in various therapeutic configurations. When used as immunotoxin conjugates (HB2-SAPORIN and OKT10-SAPORIN), the combination proved significantly more effective than either immunotoxin alone in treating T-cell acute lymphoblastic leukemia (T-ALL). In studies using SCID mice with human T-ALL cell lines, 60% of animals treated with both immunotoxins remained leukemia-free, compared to only 10% when treated with single immunotoxins.

The therapeutic synergy between these antibodies operates through multiple mechanisms. The combination delivers greater amounts of saporin to target cells positive for both CD7 and CD38, provides effective dosing to cells with downregulated expression of one antigen, and utilizes antibody-dependent cellular cytotoxicity (ADCC) mechanisms that interact additively with immunotoxin action. Studies with bispecific antibodies targeting both CD7 and CD38 demonstrated that combinations were ten times more effective than single agents, with increased rates of protein synthesis inactivation.

Native Antibody Combinations

Even the native HB2 and OKT10 antibodies (both murine IgG1 antibodies) without toxin conjugation showed therapeutic effects, likely mediated through ADCC mechanisms, though these effects were relatively weak and did not demonstrate additivity when used together. The combination of HB2-SAPORIN with native OKT10 antibody, or OKT10-SAPORIN with native HB2 antibody, produced intermediate therapeutic effects that were greater than single-agent therapy but less effective than the dual immunotoxin combination.

Clone OKT10 is a mouse monoclonal antibody that targets the CD38 antigen, a 45 kDa, type II transmembrane cell surface glycoprotein. Here are the key findings from scientific literature regarding OKT10:

Key Findings

1. Cellular Targets: OKT10 recognizes CD38 on various cell types, including precursor T and B cells, activated T cells, plasma cells, thymocytes, monocytes, and some bone marrow cells. It is particularly useful for studying mature B cell maturation and malignancies like multiple myeloma and CLL.

2. Cross-Species Reactivity: OKT10 shows cross-reactivity with primate immune cells, such as rhesus macaques, making it useful for animal research.

3. Mechanism and Epitope Mapping: The antibody binds to a specific epitope on CD38, specifically requiring the 15 C-terminal amino acids for binding. This is crucial for understanding the structural basis of CD38 recognition.

4. Applications: OKT10 is applied in various research techniques, including flow cytometry, and has been used for cell fractionation in studies involving cynomolgus macaques.

5. Therapeutic Potential: OKT10 has shown therapeutic effects in certain cancer models, such as T-cell acute lymphoblastic leukemia, when used in immunotoxin forms.

6. Membrane Antigen Expression: OKT10 can induce or reveal hidden CD38 on resting T cells upon membrane perturbation, demonstrating the dynamic nature of CD38 expression.

Overview of OKT10 Dosing Regimens in Mouse Models

OKT10 is a widely used monoclonal antibody targeting human CD38, primarily studied in mouse models of hematological malignancies such as multiple myeloma (MM). Dosing regimens vary depending on the experimental design, particularly whether OKT10 is used as a naked antibody, a component of pretargeted radioimmunotherapy (RIT), or conjugated to radionuclides.

Naked OKT10 Antibody Dosing

• In preclinical studies, the standard dose of OKT10 as a single agent is 1.4 nmol per mouse, equivalent to 300 µg. This dose is administered via injection, and the protocol typically involves a single administration followed by monitoring for tumor response.
• Efficacy: When used alone, OKT10 does not induce tumor regression or significantly delay tumor growth in MM xenograft models; tumors progress rapidly, and all animals require euthanasia by day 17 due to disease burden.
• Purpose: Naked OKT10 is primarily used as a targeting agent in combination therapies, such as pretargeted RIT, rather than as a monotherapy with intrinsic anti-tumor activity in these models.

OKT10 in Pretargeted Radioimmunotherapy (RIT)

• Pretargeting Protocol: Mice are injected with OKT10-CC (a conjugate of OKT10 with a clearing agent), followed 24 hours later by a radiolabeled effector molecule (e.g., (^{90})Y-DOTA-biotin).
• OKT10-CC Dose: The standard dose remains 1.4 nmol (300 µg) per mouse.
• Radiolabeled Effector: The dose of the radiolabeled agent varies, with studies testing 400, 800, or 1200 µCi of (^{90})Y-DOTA-biotin per mouse. All these dose levels, when combined with OKT10-CC, resulted in tumor shrinkage and prolonged survival, with 100% complete remissions achieved at the 1200 µCi dose.
• Efficacy: The combination of OKT10-CC with radioactive effector leads to rapid and complete tumor regression, in stark contrast to the lack of effect seen with OKT10 alone. Survival benefits are dose-dependent, with higher radioactivity doses offering deeper and more durable remissions.

Other Conjugated OKT10 Therapies

• Radionuclide Conjugates: In studies utilizing (^{211})At-CD38 (where the antibody is directly labeled with the alpha-emitter astatine-211), mice received 15, 30, or 45 µCi per animal in a single treatment. Higher doses (30–45 µCi) resulted in eradication of detectable disease in a majority of mice, with minimal recurrence and extended survival.
• Dosage Variation: These doses are appreciably lower (in mass) than naked antibody doses, reflecting the potency of alpha-emitter conjugates and the need to minimize radiation toxicity.

Key Variables in Dosing

• Tumor Model: The choice of xenograft (e.g., L363 for MM) and the aggressiveness of the tumor line influence the required dose and regimen.
• Combination Therapy: OKT10 is most effective as part of a pretargeted or directly conjugated therapeutic strategy, not as a standalone agent in these models.
• Route and Schedule: While most studies use intravenous or intraperitoneal injection, the timing (single dose vs. multiple doses) may vary based on the study design.

Summary Table

Conclusion

Dosing regimens of OKT10 in mouse models are highly dependent on the therapeutic strategy:

• As a naked antibody, a standard dose of 300 µg (1.4 nmol) is typical, but this confers little to no anti-tumor activity alone.
• In pretargeted RIT, the same antibody dose is used, but combined with varying amounts of radiolabeled effector (e.g., 400–1200 µCi (^{90})Y), leading to potent, dose-dependent tumor responses.
• With direct radionuclide conjugation (e.g., (^{211})At), much lower radioactivity doses (15–45 µCi) are effective, highlighting the importance of the payload in determining regimen and efficacy.

Thus, OKT10 dosing in mouse models is not one-size-fits-all: it is tailored to the experimental design, tumor model, and whether the antibody is used alone, as a targeting agent, or as part of a conjugated therapy.