Intestinal Microbiome Modulation to Enhance Anti-Tumor Immunity

University of Pittsburgh researchers have developed a novel approach to enhance anti-tumor immunity by modulating the intestinal microbiome. This method involves the use of responder-derived fecal microbiota transplant (FMT) in combination with anti-PD-1 therapy to treat PD-1 refractory melanoma patients. The combination therapy has shown to be well-tolerated, providing clinical benefits and inducing rapid and durable changes in the gut microbiome, which reprograms the tumor microenvironment to overcome resistance to anti-PD-1 therapy.

Clinical trial response data of FMT with anti-PD-1 therapy in melanoma patients. Radiographic change of tumor burden from baseline. n=15

Description

The invention leverages the correlation between gut microbiota composition and the efficacy of anti-PD-1 therapy. Researchers designed a clinical trial to evaluate the safety and efficacy of combining responder-derived FMT with anti-PD-1 therapy in melanoma patients. The results demonstrated that this combination therapy increased the abundance of beneficial taxa and was associated with enhanced anti-tumor immunity, including increased CD8+ T cell activation and reduced IL-8 levels.

Applications

• Treatment of PD-1 refractory melanoma
• Enhancement of anti-tumor immunity in cancer patients
• Potential application in other cancers responsive to anti-PD-1 therapy

Advantages

This technology offers a novel approach to overcoming resistance to anti-PD-1 therapy by modulating the gut microbiome. The combination of FMT and anti-PD-1 therapy is well-tolerated and provides clinical benefits. The method identifies specific microbiota associated with enhanced clinical response, offering a targeted approach to improving cancer treatment outcomes. The findings also provide a means to identify cancer patients who may benefit from microbiome-specific interventions, with significant biotherapeutic potential.

Invention Readiness

The invention is currently supported by in vivo data from a clinical trial demonstrating the safety and efficacy of the combination therapy. Further development includes optimizing the FMT process and expanding the application to other cancers and patient populations. Ongoing research aims to refine the understanding of the microbiome's role in anti-tumor immunity and develop standardized protocols for clinical use.

IP Status

https://patents.google.com/patent/US20240041931A1