Columbia Technology Ventures

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:

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