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Novel Targeted mtLivin Nanoparticles for Improved Resistant Cancer Therapy

Benita Simon, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research

 

Category

LifeSciences and BioTechnology   

Keywords

Cancer resistance,

Current development stage

TRL3 - hypothesis testing and initial POC demonstrated

 Application

The resistance of tumor cells to drug-induced apoptosis is a major cause for the failure of various cancer treatments. The mtLitvin-targeted bifunctional nanoparticles are a personalized approach for treating resistant cancer, especially liquid tumors. Additional CD40+ types of NHL and other leukemias/ lymphomas also may be treatable with mtLivin-CD40L-NPs coupled with chemotherapy.

Innovation
A PLGA-based delivery system  with a cancer specific targeting agent  for the administration of  truncated pro-apoptotic form of Livin protein (mtLivin)  selectively to diffuse large B-cell lymphoma (DLBCL) cells.  A product design shows enhancements in stability, bioavailability, and cellular uptake. This product candidate may be given to subjects with chemotherapy.

Findings

Targeted mtLivin nanoparticles elicited significant cell death of DLBCL cells, much higher than achieved by treatment with mtLivin-NPs. 

To best mimic human lymphoma, a disseminated lymphoma model was used to evaluate the anti-tumor effect of targeted mtLivin treatment. With time, lymphoma infiltrations were detected in brain, bone marrow, lungs, spleen and liver. All control mice exhibited paralysis and died within 28 days. In contrast, 71% of mice receiving mtLivin-CD40L-NPs achieved a complete pathological tumor response and survived significantly longer than 28 days.

Treatment was well-tolerated. 

Tumors from treated mice showed high caspase-3 activity, thereby demonstrating the ability of the bifunctional NPs to target tumors and induce apoptotic tumor cell death. 

Opportunity

For some types of aggressive tumors chemotherapy often cures up to ~50% of patients, and the five-year survival rate is only ~60%. Thus, there is a significant pool of patients that are resistant to treatment, many because of resistance to chemotherapy-induced apoptosis.

This targeted therapy should be selective for tumor cells. The Livin moiety of the therapy, once internalized to the tumor cell, will induce apoptosis. By overcoming regular drug-induced apoptosis, which is a major mechanism of resistance to chemotherapy, this candidate given with chemotherapy can offer a unique therapeutic option over conventional antibody therapy such as Rituxan that targets the tumor without overcoming drug-induced apoptosis.

 

 

 

 

Contact for more information:

Ariela Markel
VP, Business Development, Healthcare
+972-2-6586608
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