Tumor-penetrating peptide for enhancing immunotherapy in solid tumors

\This technology is a peptide-based therapeutic that remodels the tumor microenvironment to sensitize resistant solid tumors, such as pancreatic cancer, to existing immunotherapies.

Unmet Need: Targeted method to overcome immunotherapy resistance in solid tumors

While immune checkpoint inhibitors have revolutionized patient outcomes, their efficacy against solid tumors like pancreatic cancer is severely limited by the immunosuppressive tumor microenvironment (TME) that blocks cytotoxic T-cells. Systemically depleting immunological barriers such as regulatory T cells or TGF-β signaling to overcome this resistance can result in autoimmune toxicities and can accelerate disease progression. Consequently, there is a critical need for targeted, tumor-localized TME modulators that can safely dismantle this protective barrier to sensitize tumors to immunotherapies.

The Technology: Tumor-penetrating peptide that sensitizes solid tumors to immunotherapy

This technology utilizes a targeted tumor-penetrating peptide (iRGD) to selectively degrade the physical and immunological barriers within desmoplastic solid tumors. The peptide functions by engaging receptors specifically localized within the tumor microenvironment to inhibit the activation of TGF-β and disrupt regulatory T-cell (Treg) stability. By restricting this pathway inhibition to the tumor site, the technology effectively depletes immunosuppressive intratumoral Tregs and reduces dense tumor fibers without disrupting normal immune functions. This localized immunomodulation improves vascular perfusion and enables cytotoxic CD8+ T-cells to successfully infiltrate the tumor.

This technology has been validated in vivo using mouse models of pancreatic cancer.

Applications:

• Combination immunotherapy for desmoplastic solid tumors
• Enhancement of chemo-immunotherapy regimens
• Tumor microenvironment (TME)-modifying agent
• Biomarker-guided patient selection

Advantages:

• Limits systemic autoimmune toxicities
• Preserves peripheral immune function
• Selectively targets the tumor microenvironment
• Compatible with existing standard-of-care immunotherapies
• Improves vascular perfusion to tumors

Lead Inventor:

Kazuki Sugahara, MD, PhD

Patent Information:

Patent Pending (US20240000883)

Related Publications:

• Hurtado de Mendoza T, Mose ES, Botta GP, et al. “Tumor-penetrating therapy for β5 integrin-rich pancreas cancer” Nat Commun. 2021 Mar 5; 12(1): 1541.

• Sugahara KN, Teesalu T, Karmali PP, et al. “Tissue-penetrating delivery of compounds and nanoparticles into tumors” Cancer Cell. 2009 Dec 8; 16(6): 510-520.

Tech Ventures Reference:

• IR CU26104

• Licensing Contact: Jerry Kokoshka