Peptide for sensitizing cancers to immunotherapy

This technology is an immunomodulatory peptide that alters tumor microenvironments to improve patient outcomes and survival in cancers resistant to immunotherapies.

Unmet Need: Enhanced effectiveness of immunotherapy against cancer

Many types of cancer, such as pancreatic ductal adenocarcinoma (PDAC), are resistant to chemo- and immunotherapy. Immunotherapy-resistant tumors are characterized by a microenvironment enriched in regulatory T cells (Tregs), which suppress the immune system’s ability to attack the tumor and limit the effectiveness of immunotherapies. Although there is a need for strategies that sensitize these cancers to immunotherapy, systemic depletion of Tregs is not a viable solution due to side effects such as autoimmune toxicity.

The Technology: iRGD peptides for increasing efficacy of existing cancer therapeutics

This technology describes the ability of tumor internalizing (iRGD) peptides to sensitize PDAC and other cancers to immunotherapy by depleting immunosuppressive Tregs in a tumor-specific manner. This results in a localized expansion of effector CD8+ T cells, which attack the tumor without the inflammatory side effects associated with systemic Treg depletion. As such, iRGD peptides prevent tumor resistance, reduce tumor burden, and prolong survival.

This technology has been validated in a PDAC mouse model.

Applications:

• Sensitizing agent in combination with immunotherapy
• Tumor-infiltrating regulatory T cell-depleting agent for cancer treatment
• Intraperitoneal and systemic chemotherapy
• Treating PDAC and other refractory cancers such as sarcoma and ovarian cancer

Advantages:

• Sensitizes PDAC and other cancers to immunotherapy
• Enhances efficacy of existing cancer therapeutics
• Depletes Tregs selectively in cancer tissue
• Avoids inflammatory side effects of systemic Treg depletion
• Simple co-administration to chemotherapy
• Improves patient outcomes
• Improves overall survival in several immunotherapy-resistant cancers
• Prevents tumor resistance

Lead Inventor:

Kazuki Sugahara, M.D., Ph.D.

Patent Information:

Patent Pending(US20240000883)

Related Publications:

• Simon-Gracia L, Hunt H, Scodeller PD, Gaitzsch J, Kotamraju VR, Sugahara KN, Tammik O, Ruoslahti E, Battaglia G, Teesalu T. “iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes” Biomaterials 2016 Oct; 104:247 57.

• Sugahara KN, Scodeller P, Braun GB, de Mendoza TH, Yamazaki CM, Kluger MD, Kitayama J, Alvarez E, Howell SB, Teesalu T, Ruoslahti E, Lowy AM. “A tumor-penetrating peptide enhances circulationindependent targeting of peritoneal carcinomatosis” J Control Release 2015 Aug 28; 212:59-69.

• Hamilton AM, Aidoudi-Ahmed S, Sharma S, Kotamraju VR, Foster PJ, Sugahara KN, Ruoslahti E, Rutt BK. “Nanoparticles coated with the tumor-penetrating peptide iRGD reduce experimental breast cancer metastasis in the brain” J Mol Med 2015 Apr 14; 93:991-1001.

• Sugahara KN, Braun GB, de Mendoza TH, Kotamraju VR, French R, Lowy AM, Teesalu T, Ruoslahti E. “Tumor-penetrating iRGD peptide inhibits metastasis” Mol Cancer Ther 2015 Jan; 14:120-8.

Tech Ventures Reference:

• IR CU21100, CU23106

• Licensing Contact: Jerry Kokoshka