Combination therapy for the treatment of melanoma

This technology describes a therapeutic strategy that combines a selective NF-kB pathway inhibitor with an immune checkpoint inhibitor for the treatment of drug-resistant melanoma.

Unmet Need: Selective NF-kB pathway inhibition for targeted melanoma treatment

While treatment of early-stage melanoma is highly effective, late-stage metastatic melanoma remains highly resistant to traditional chemotherapies. Hyperactivity of the NF-kB pathway has been shown to stimulate melanoma tumor growth through the activity of regulatory T-cells (Tregs), but current broad-spectrum NF-kB inhibitors have not been effective against melanoma due to undesirable side effects. As such, there is a need for selective NF-kB inhibitors that can target Tregs to prevent tumor growth and relapse.

The Technology: Selective NF-kB inhibition enhances immune checkpoint-blockade therapy

This technology describes the use of a specific NF-kB inhibitor to enhance immune checkpoint-blockade treatment of metastatic melanoma. This technology is based on the finding that ablation of the NF-kB subunit c-Rel specifically impairs the generation and maintenance of the activated Treg subset, which are known to be enriched at tumor sites. By specifically targeting c-Rel with the approved compound pentoxifylline, this technology provides a secondary mechanism to target metastatic melanoma that can be combined with existing immune checkpoint-blockade treatment to both increase treatment efficacy and reduce drug resistance.

This technology has been validated with mice injected with B16F1 melanoma.

Applications:

• Immunotherapy for metastatic or drug-resistant melanoma
• Combination therapy using immune-checkpoint blockade strategy
• Treatment of inflammatory disorders involving the NF-kB pathway
• Modulation of regulatory T cells
• Potentiation of other immune therapies

Advantages:

• Pentoxifylline is already approved for other uses
• Selective inhibition of the NF-kB pathway prevents undesirable side effects
• Compatible with checkpoint-blockade therapies

Lead Inventor:

Sankar Ghosh, Ph.D.

Patent Information:

Patent Pending (WO/2017/058881)

Related Publications:

• Oh H, Grinberg-Bleyer Y, Liao W, Maloney D, Wang P, Wu Z, Wang J, Bhatt DM, Heise N, Schmid RM, Hayden MS, Klein U, Rabadan R, Ghosh S. “An NF-κB Transcription-Factor-Dependent Lineage-Specific Transcriptional Program Promotes Regulatory T Cell Identity and Function.” Immunity. 2017 Sep 19; 47(3): 450-465.

• Grinberg-Bleyer Y, Oh H, Desrichard A, Bhatt DM, Caron R, Chan TA, Schmid RM, Klein U, Hayden MS, Ghosh S. “NF-kB c-Rel is Crucial for the Regulatory T Cell Immune Checkpoint in Cancer.” Cell. 2017 Sep 7; 170(6): 1096-1108.

Tech Ventures Reference:

• IR CU16039

• Licensing Contact: Cynthia Lang