Anti-Mouse/Human TYRP1/TRP1 (Clone TA99) – Purified in vivo GOLD™ Functional Grade

The TA-99 clone is a monoclonal antibody that targets tyrosinase-related protein 1 (TYRP1), also known as glycoprotein 75 (gp75). This protein is expressed on the surface of certain melanoma cells, such as the B16F10 cell line. Here are some common in vivo applications of the TA-99 clone in mice:

1. Melanoma Models: TA-99 is used in mouse models of metastatic melanoma, particularly to study the efficacy of antibody-based therapies targeting gp75. It has been shown to effectively prevent lung metastases in models of B16 cells, which express gp75.

2. Tumor Clearance Studies: The antibody is used to explore its effector functions, such as activating immune cells like natural killer (NK) cells and priming CD8+ T cells, which are crucial for antitumor activity.

3. Evaluation of Immune Responses: TA-99 is utilized to assess the impact of modifications in antibody structure, such as fucosylation levels, on immune activation and tumor clearance. For instance, afucosylated variants of the antibody have enhanced binding to certain mouse Fc receptors, which can improve therapeutic efficacy.

4. Preclinical Development: The TA-99 clone is also used in developing CAR-T cell therapies that target TYRP1/gp75-expressing cells, demonstrating its potential in targeted cancer treatments.

Overall, the TA-99 clone is a valuable tool in preclinical cancer research, particularly for studying targeted therapies in mouse models.

Commonly Used Antibodies and Proteins with TA-99 in the Literature

TA-99 is a well-characterized monoclonal antibody targeting tyrosinase-related protein 1 (Tyrp1, also known as TRP1 or gp75), primarily studied in murine melanoma (B16) models. Its combination with other antibodies, cytokines, and vaccines has been explored to enhance anti-tumor immunity and therapeutic outcomes.

Frequently Combined Agents

Key Scientific Insights

• Vaccine Combinations: TA-99 is often paired with DNA vaccines against Tyrp1 and gp100, resulting in enhanced CD8+ T cell infiltration and systemic reactivity against tumor antigens. The combination also induces epitope spreading, broadening the immune response beyond the original vaccine target.
• Cytokine Augmentation: IL-2, a potent T cell growth factor, is used to amplify the effects of TA-99, especially in the context of adoptive T cell transfer and vaccination.
• Immune Checkpoint Modulation: Anti-PD1 checkpoint inhibitors are combined with TA-99-based therapies to overcome immune evasion by tumors.
• Agonist Antibodies: Anti-4-1BB antibodies prevent activation-induced death of T cells and further amplify the anti-tumor response initiated by TA-99.
• Treg Depletion: Transient depletion of regulatory T cells (via anti-CD25) enhances the efficacy of TA-99, though the timing of depletion is crucial to avoid compromising effector T cell responses.
• Innate Immune Stimulation: TLR ligands are used to activate innate immunity, complementing the adaptive response driven by TA-99.
• Engineered Antibody-Cytokine Fusions: TA99-Neo2/15, an antibody-cytokine chimera, represents a next-generation approach, showing synergy with checkpoint blockade and multi-antigen vaccination.

Summary Table of Common Combinations

Conclusion

TA-99 is most commonly used in combination with DNA vaccines (Tyrp1, gp100), cytokines (IL-2), immune checkpoint inhibitors (anti-PD1), agonist antibodies (anti-4-1BB), Treg-depleting agents (anti-CD25), and TLR ligands to enhance anti-tumor immunity in preclinical melanoma models. These combinations aim to overcome tumor immune evasion, broaden antigen recognition, and sustain effective T cell responses. Engineered antibody-cytokine fusions like TA99-Neo2/15 represent an advanced strategy, showing promise when combined with checkpoint blockade and multi-antigen vaccination.

Key findings from scientific literature citing clone TA-99 focus on its use as a tool and therapeutic in immuno-oncology, specifically targeting tyrosinase-related protein 1 (TRP1/gp75) expressed in melanocytes and melanoma cells.

Essential findings include:

• Target specificity and applications: TA-99 is a well-characterized mouse monoclonal antibody that recognizes human and mouse TRP1 (TYRP1, gp75), a glycoprotein involved in pigmentation. Its specificity has made it a standard marker for studying melanocyte biology and melanoma in laboratory research.

• Cancer research and therapy: TA-99 has played a significant role in preclinical melanoma models, where it is used both for tumor detection (immunohistochemistry, Western blot) and as a therapeutic antibody. Notably, it has been foundational in assessing the immune response to melanoma, contributing to a better understanding of antibody-mediated tumor control.

• Immunotherapy combinations: Experiments in mice show that combining TA-99 with immune-modulating strategies—such as immune checkpoint inhibitors or regulatory T cell depletion—enhances its anti-tumor effects. For example, TA-99 plus MEK inhibitor and immune checkpoint blockade led to improved therapeutic outcomes in melanoma models.

• Mechanistic insights: Studies reveal that the efficacy of TA-99 in mobilizing adaptive immunity is tightly regulated by immune suppression (e.g., regulatory T cells, immune checkpoints). Effective combination therapies involve TA-99 and regulatory-targeted agents to overcome immune resistance.

• Biotechnological innovations: TA99 has been linked to novel cancer immunotherapies such as antibody-cytokine fusion proteins and CAR-T cells targeting TRP1, broadening its translational potential for melanoma treatment.

• Historical and technical context: Clone TA-99 was developed in the mid-1980s via hybridoma technology with the aim of generating antibodies reactive with melanoma antigens. It remains a reference antibody for TRP1 in research settings.

Summary Table: Key Applications and Findings for Clone TA-99

The collective literature indicates clone TA-99 is a pivotal reagent in melanoma biology and immunotherapy preclinical research, with significant evidence supporting its use as a therapeutic antibody, particularly in combination strategies.

Dosing regimens of the anti-tyrosinase-related protein-1 monoclonal antibody clone TA-99 vary by mouse model, experimental context, and the immunological background of the mice. Studies predominantly use C57BL/6 or specialized genetically engineered mice for melanoma and immunotherapy research.

Key differences in dosing regimens include:

• Dose Amount and Frequency:

  • In typical C57BL/6 B16 melanoma models, TA-99 is administered at 200 µg per mouse intraperitoneally (i.p.) on days 5 and 7 or 5 and 9 after tumor inoculation. This two-dose schedule is supported by multiple studies focused on immune modulation and Treg depletion.
  • Other regimens utilize up to four doses at intervals determined by tumor or immune cell kinetics, especially in models designed to tolerate repeated dosing.

• Routes of Administration:

  • Most commonly, TA-99 is delivered intraperitoneally (i.p.).
  • In models requiring rapid systemic exposure, intravenous (i.v.) injection is used, especially in metastasis models where B16-F10 cells are injected i.v. followed by TA-99 doses.

• Specialized Mouse Models:

  • In knock-in mice expressing humanized IgG1 Fc regions (to model human FcγR biology and minimize immune clearance), repeated TA-99 administration is feasible without rapid clearance due to anti-drug antibody formation—unlike standard mice where anti-human IgG responses limit dosing.
  • In such models, four doses of a TA-99 hIgG1 variant are administered post tumor inoculation, enabling study of both efficacy and immunogenicity under chronic dosing.

• Combination Therapy Contexts:

  • TA-99 is often given in combination with cytokines (e.g., IL-2, IFNα) or immune checkpoint inhibitors, altering dosing timing (often staggered or concurrent with other agents) and requiring careful schedule harmonization.
  • The combination with Treg depletion, for instance, sets TA-99 on days 5 and 7 after tumor cells, with adjunct therapy (e.g., anti-CD25 mAb) added at later time points.

• Dose Range and Toxicity:

  • High single doses (300–1000 µg) have been associated with off-target effects (e.g., mouse depigmentation), and so lower doses (≤200 µg per injection) are used in most tumor and combination studies to balance efficacy and safety.

Summary:
Most studies standardize on 200 µg i.p. on two separate days post-tumor inoculation for routine immunotherapy or tumor challenge models in C57BL/6 mice, whereas genetically engineered, humanized models support repeated or variant dosing regimens to study long-term effects and human-specific antibody variants. Combination protocols may further adapt the regimen to synchronize with other immune-modulating agents. High-dose applications are rare and primarily used for mechanistic or toxicity studies.