Next-Generation Humanized Nanobody Targeting LRRC32 and TGFB1 for Advanced Breast Cancer Therapy
VHH-P357 is a humanized single-domain antibody nanoparticle specifically engineered to target the glycoprotein-A repetitions predominant-transforming growth factor beta 1 complex. This novel nanobody acts against leucine rich repeat containing 32 (LRRC32) and transforming growth factor beta 1 (TGFB1), making it a promising candidate for the treatment of breast cancer. Currently in the Biological Testing stage, VHH-P357 combines a humanized variable heavy chain domain with an Fc fragment, designed to enhance effector functions. Its rational design aims to disrupt key pathological signaling in breast cancer, paving the way for innovative therapeutic strategies.
| Candidate | VHH-P357 |
| Target | leucine rich repeat containing 32 (LRRC32) transforming growth factor beta 1 (TGFB1) |
| Modality | humanized bispecific VHH |
| Indication | Breast Cancer |
Licensing Opportunity
VHH-P357 is open for out-licensing and collaboration opportunities. We welcome inquiries from partners seeking to advance or co-develop this innovative nanobody program for breast cancer therapy.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P357 |
Modality
VHH-P357 represents a cutting-edge therapeutic modality utilizing a humanized single-domain antibody (nanobody) structure, fused to a human IgG4 Fc fragment with a S228P mutation. The nanobody format offers distinct advantages, such as extremely small size, high tissue penetration, and exceptional stability, supporting more effective targeting of tumor microenvironments in breast cancer. The fusion with the Fc region provides extended serum half-life and potential for effector function engagement. Collectively, this modality integrates the unique pharmacokinetics of nanobodies and the advantageous immune properties of IgG4, resulting in a therapy designed for both precision and durability in breast cancer treatment.
Target
LRRC32 and TGFB1 are pivotal molecular targets in cancer biology. LRRC32 is a transmembrane protein primarily expressed on regulatory T cells and some cancer cell surfaces, implicated in immune tolerance and modulation of the tumor microenvironment. TGFB1, a multifunctional cytokine, is broadly involved in cell proliferation, differentiation, and immune responses, and is often upregulated in various cancers, including breast cancer. The LRRC32/TGFB1 axis contributes to tumor growth, immune evasion, and metastasis. Targeting LRRC32 and TGFB1 in breast cancer is supported by evidence linking their dysregulation to poor patient outcomes and resistance to standard therapies. VHH-P357’s focus on LRRC32 and TGFB1 offers strategic value by disrupting critical immunosuppressive pathways, providing a differentiated therapeutic approach for breast cancer.
Mechanism of Action
VHH-P357 operates by selectively binding and inhibiting the LRRC32/TGFB1 complex at the tumor site. By targeting this specific complex, VHH-P357 disrupts the activation and release of immunosuppressive TGFB1 driven by LRRC32, thereby modulating the tumor immune microenvironment. This action enhances anti-tumor immune activity and may overcome resistance mediated by immunosuppressive signaling. As a nanobody-based platform, VHH-P357 provides opportunities for further development, including as the basis for antibody-drug conjugates (ADCs), bispecific formats, or molecular imaging agents. Its precise mechanism and modular design support the advancement of next-generation immunotherapies for breast cancer.
Breast Cancer
Breast cancer is one of the most prevalent malignancies worldwide, significantly impacting women's health and representing a leading cause of cancer-related mortality. It encompasses a heterogeneous group of diseases, with diverse molecular subtypes and clinical outcomes. Standard treatments include surgery, chemotherapy, radiotherapy, hormone therapy, and targeted therapies. Although these approaches have improved survival, many patients experience limited efficacy due to drug resistance, recurrence, or the failure to eliminate metastatic and immunosuppressive disease components. There remains a substantial unmet need for novel therapies that can more specifically target tumor-promoting pathways and modulate the immune microenvironment. VHH-P357, by specifically targeting LRRC32 and TGFB1, presents a new therapeutic avenue with potential to overcome traditional therapy resistance and enhance clinical outcomes in breast cancer patients.