FCRLA as a Target for Immunotherapy of B-cell Lymphoma

Antibody-based therapy restores immune recognition in B-cell lymphoma by blocking a tumor-secreted immune evasion protein.

Institute Reference: P1839

Matthieu, https://stock.adobe.com/408171568, stock.adobe.com (2nd picture down)

Background

B-cell lymphomas such as Burkitt lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL) are aggressive hematologic malignancies with limited durable treatment options. A major barrier to effective and lasting immune response in these cancers is the tumor’s ability to evade immune detection, particularly by impairing antigen presentation via the HLA class II pathway. This leads to poor activation of CD4+ T cells, which are essential for coordinating robust and lasting anti-tumor responses. While treatments like CAR T-cell therapy and antibody-drug conjugates show promise, they come with challenges related to toxicity, cost, and durability. There is an urgent need for immunotherapies that restore immune function without broadly suppressing or depleting immune cells.

Technology Overview

This technology introduces a novel immunotherapeutic strategy designed to overcome immune evasion in B-cell lymphomas. It focuses on restoring functional antigen presentation to CD4+ T cells, a process that is frequently impaired in aggressive subtypes, such as diffuse large B-cell lymphoma, follicular lymphoma, and Burkitt lymphoma.

The approach targets a tumor-associated immune-suppressive mechanism that interferes with antigen presentation and T-cell activation. By neutralizing this pathway using antibody-based tools, the invention enhances immune recognition of malignant cells and improves anti-tumor responses in preclinical models. The strategy also offers diagnostic potential, as elevated levels of a tumor-derived factor correlate with poor patient outcomes.

This platform has potential as a stand-alone immunotherapy or as a complementary agent in combination with existing lymphoma treatments, offering a more targeted and less toxic approach to restoring immune function.

Benefits

• Novel Immune Evasion Target: Secreted FCRLA is a previously unrecognized mechanism by which B-cell lymphomas suppress antigen presentation to CD4+ T cells.
• Restores T-cell Activation: Antibody blockade restores CD4+ T cell responses and boosts anti-tumor immunity.
• Prognostic Biomarker: Serum FCRLA levels correlate with survival outcomes in B-cell lymphoma patients, enabling patient stratification.
• Combination Therapy Potential: FCRLA inhibition may synergize with CAR-T cells or checkpoint inhibitors by lifting immune suppression.
• Lower Toxicity Profile: Targeting a secreted molecule rather than broadly depleting immune cells could offer improved safety and reduced off-target effects.

Applications

• Immunotherapy for B-cell Lymphomas: Development of monoclonal antibodies or other inhibitors to neutralize secreted FCRLA in cancers such as DLBCL, follicular lymphoma, and Burkitt lymphoma.
• Diagnostic Development: Use of serum FCRLA levels as a prognostic tool to guide treatment intensity or enrollment in targeted immunotherapy trials.
• Research Tools: Reagents targeting FCRLA may support studies in antigen presentation, immune escape, and tumor immunology.
• Combination Regimens: Potential to improve outcomes in patients treated with checkpoint inhibitors, CAR-T, or other immunotherapies.

Opportunity

The global lymphoma therapeutics market is expected to surpass $15 billion by 2030, with strong demand for next-generation immunotherapies that address immune evasion. This invention introduces a novel approach that targets a tumor-secreted immune suppressor, unlocking a new mechanism to boost CD4+ T cell responses and improve immunotherapy outcomes. Importantly, the relevance of this target extends beyond lymphoma; several subtypes of renal cell carcinoma and melanoma also express FCRLA, suggesting that this platform could have broader applications across multiple malignancies where immune evasion remains a major barrier to successful treatment.

The Medical University of South Carolina is currently seeking commercial partners, biotech collaborators, or investors interested in advancing this FCRLA-targeted immunotherapy. The opportunity includes potential licensing of therapeutic antibodies and development of a companion diagnostic tool for patient risk stratification.

Patents

• 63/894,941

Seeking

• Development partner
• Licensing
• Commercial partner
• Seeking investment

IP Status

• Provisional patent