Dual targeting of epigenetically amplified lymphomas via epigenetic modifiers and immune checkpoint inhibition

This technology combines anti-PD-1 antibodies with epigenetic modifiers to overcome resistance and improve therapeutic outcomes in lymphoma treatment.

Unmet Need: Overcoming therapeutic resistance in primary mediastinal B-cell lymphoma

Primary mediastinal B-cell lymphoma (PMBCL) is an aggressive malignancy that is frequently associated with amplification of chromosome 9p24.1 in up to 75% of patients. This genetic alteration drives overexpression of PD-L1, PD-L2, and JAK2, altering the cell’s epigenetic landscape. As a result, PMBCL shows limited responsiveness to immune checkpoint blockade. Epigenetic therapies alone have also failed to deliver meaningful clinical benefits. These limitations highlight a critical need for alternative strategies that can more effectively target the underlying epigenetic and immune resistance mechanisms of PMBCL.

The Technology: Dual-targeted approach for improved lymphoma treatment outcomes

The technology is a dual-targeted approach for the treatment of primary mediastinal B-cell lymphoma (PMBCL). The conjunction of epigenetic reprogramming agents with immune checkpoint inhibitors like anti-PD-1 antibodies shows synergistic effects, increasing tumor immunogenicity and reducing resistance. This approach reverses epigenetic silencing, reconditions the tumor microenvironment, and amplifies the effectiveness of existing immune checkpoint therapies. The technology offers a promising avenue to overcome immune escape mechanisms in PMBCL, holding the potential for significantly improved outcomes in patients.

This technology has been validated in vivo using mouse models.

Applications:

• Immunotherapy for cancer treatment
• Treatment for relapsed/refractory lymphomas
• Research model for studying the impact of the 9p24.1 amplification in lymphomas and other cancers

Advantages:

• Synergizes immune checkpoint inhibitors with epigenetic agent modifiers
• Reverses epigenetic silencing
• Increases tumor immunogenicity
• Reduces treatment resistance

Lead Inventor:

Jennifer Amengual, M.D.

Patent Information:

Patent Pending

Related Publications:

• Seda S. Tolu, Ted B. Piorczynski, Manuel Pazos, II, Brian Estrella, Hua-Jay J Cherng, Barbara Pro, Jennifer E. Amengual. “Combination JAK Inhibition and Immune Checkpoint Blockade for the Treatment of 9p Amplified Lymphomas.” Blood. 2024 Nov 5; 144(1): 336.

Tech Ventures Reference:

• IR CU24177

• Licensing Contact: Kristin Neuman