MACTIDE-V | CD206-Targeted Peptide-Drug Conjugate for TAM Modulation and Cancer Research

Description

Product Description

MACTIDE-V is an advanced peptide-drug conjugate (PDC) designed for the selective targeting and modulation of CD206⁺ tumor-associated macrophages (TAMs). It represents a novel strategy in cancer immunotherapy and tumor microenvironment (TME) reprogramming, providing a powerful research tool for studying macrophage-driven tumor progression and immune suppression.

The compound consists of a macrophage-targeting peptide (MACTIDE) linked to Verteporfin, a small-molecule photosensitizer known for its inhibitory effect on the Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) signaling pathway. Upon binding to CD206, a mannose receptor highly expressed on TAMs, MACTIDE-V selectively delivers Verteporfin to these immunosuppressive cells, enabling precise reprogramming of the tumor immune microenvironment.

Research Significance

Tumor-associated macrophages represent a major component of the tumor stroma and play a pivotal role in supporting cancer growth, metastasis, angiogenesis, and immune evasion. The CD206 receptor, or mannose receptor C-type 1 (MRC1), is highly expressed in M2-like macrophages that promote tumor progression through secretion of IL-10, VEGF, and other immunosuppressive mediators. Targeting these macrophages has emerged as a promising therapeutic and research strategy.

MACTIDE-V’s selective targeting allows for potent inhibition of the YAP/TAZ signaling pathway in TAMs, leading to YAP exclusion from the nucleus. This action shifts macrophage polarization from a pro-tumoral M2 phenotype toward an anti-tumoral M1 phenotype, characterized by enhanced antigen presentation, increased phagocytosis, and secretion of pro-inflammatory cytokines such as TNF-α and IL-12.

Functional Outcomes

• Immune Activation: Reprogrammed TAMs enhance infiltration of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells into the tumor microenvironment.

• Suppression of Metastasis: In triple-negative breast cancer (TNBC) mouse models, MACTIDE-V significantly reduces both primary tumor volume and lung metastatic nodules.

• Pathway Regulation: Inhibits YAP/TAZ transcriptional coactivators, reducing proliferation and migration signals in cancer cells indirectly through macrophage modulation.

• Oral Bioavailability: Unlike most peptide conjugates, MACTIDE-V demonstrates oral activity, providing convenience and translational potential in research applications.

Collectively, MACTIDE-V serves as a next-generation immunomodulatory research compound for investigating macrophage biology, tumor immunology, and targeted delivery systems.

Product Specifications

Mechanism of Action

MACTIDE-V’s mechanism of action is centered on targeted macrophage modulation and immune reactivation through YAP/TAZ signaling suppression.

1. CD206-Mediated Targeting

CD206, also known as MRC1, is a mannose-binding receptor overexpressed on M2-like TAMs. MACTIDE-V’s peptide backbone has high affinity for CD206, ensuring selective internalization via receptor-mediated endocytosis. Once internalized, the conjugated Verteporfin is released intracellularly, enabling localized inhibition of YAP/TAZ activity within the macrophage.

2. YAP/TAZ Inhibition and Macrophage Repolarization

The Hippo-YAP/TAZ signaling pathway regulates cellular proliferation, differentiation, and immune suppression. Verteporfin delivered via MACTIDE-V binds YAP and disrupts its interaction with TEAD transcription factors, preventing its nuclear translocation.
As a result, TAMs undergo a phenotypic shift from an M2 (tumor-promoting) to M1 (tumor-suppressing) phenotype. The M1 macrophages release pro-inflammatory cytokines, enhance phagocytosis, and increase tumor antigen presentation, amplifying adaptive immune responses.

3. Immune Microenvironment Modulation

Repolarized TAMs reduce tumor immune evasion by:

• Increasing CD8⁺ T-cell infiltration and NK cell activation.

• Promoting cytotoxic activity and antigen presentation.

• Reducing levels of IL-10, VEGF, and TGF-β, which are key immunosuppressive mediators.

4. Suppression of Tumor Growth and Metastasis

In TNBC mouse models, MACTIDE-V effectively suppresses both primary tumor growth and secondary metastasis (especially to the lungs). This suppression results from synergistic mechanisms involving immune activation, decreased angiogenesis, and reprogramming of the tumor microenvironment to an anti-tumoral state.

5. Significance in Research

MACTIDE-V enables exploration of:

• TAM-targeted therapy development

• Mechanistic studies on YAP/TAZ pathway inhibition

• Cross-talk between macrophages and tumor immunity

• Development of orally active peptide-drug conjugates

  

Side Effects

As a research compound, MACTIDE-V is not approved for therapeutic use. However, based on mechanistic studies and in vivo research data, several laboratory-observed effects have been reported:

• Cytokine Elevation: Increased TNF-α and IL-12 release due to macrophage activation.

• Transient Inflammation: Local inflammatory responses observed in some animal models.

• Mitochondrial Stress: Moderate oxidative stress resulting from YAP inhibition and macrophage reprogramming.

• Hepatic Uptake: As CD206 is also expressed in liver macrophages (Kupffer cells), hepatic accumulation may occur.

• Immune Modulation: Enhanced adaptive immune activation could influence experimental immune balance.

Proper safety protocols should be observed when handling MACTIDE-V, including PPE use and controlled dosing during in vivo experiments.

Disclaimer

For research use only. Not intended for human or veterinary use, diagnosis, or treatment. Handle only by trained laboratory personnel under approved biosafety conditions.

Keywords

MACTIDE-V, CD206-targeted conjugate, TAM modulation, Verteporfin peptide, YAP/TAZ inhibitor, macrophage reprogramming, tumor immunology, TNBC research, anti-tumor immune activation, peptide-drug conjugate.

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