TECHNOLOGY/BUSINESS OPPORTUNITY Protein mediated immune cell engineering

Opportunity:

Lawrence Livermore National Laboratory (LLNL), operated by the Lawrence Livermore National Security (LLNS), LLC under contract no. DE-AC52-07NA27344 (Contract 44) with the U.S. Department of Energy (DOE), is offering the opportunity to enter into a collaboration to further develop and commercialize its “protein mediated immune cell engineering” technology.

Background:

Chimeric Antigen Receptor (CAR) therapies modify the patient’s own T lymphocytes (autologous) ex vivo and then inject them back into the patient’s body to kill cancer cells. CAR-T cells express hybrid (chimeric) molecules that contain an antibody-binding fragment (scFV) derived from an antibody and intracellular signaling domain(s) from the T-cell receptor. CAR-T cells then bind to specific antigens on the surface of cancer cells resulting in T cell activation and tumor killing.

Typically, a virus is used to introduce the gene for CAR into the T-cells then the cells are activated and amplified ex vivo. The disadvantages of using viral vectors for the delivery of the CAR gene are (i) time-consuming manufacturing that takes 3+ weeks at a GMP facility, (ii) cost (>$300K), and (iii) risk of cancer arising from viral integration in host cells.

Description:

Rather than using genes carried by viruses, LLNL researchers have developed an alternative approach of delivering CAR to T-cells in form of proteins that are carried on the surface of nanolipoprotein (NLP) particles. NLPs are naturally occurring molecules that serve as structural mimics of cell membranes.  They can self-assemble and provide a structure or platform for connecting other molecules.

CAR proteins integrated into NLPs show high solubility and appropriate binding to their ligand.  Culturing T cells with NLPs results in transfer of CAR proteins into human T cells with minimal toxicity, resulting in a population of CAR expressing T cells with no genetic alterations.

For more information regarding the patented method and systems for producing NLP particles (https://image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/11300572), which is also available for licensing from the Lab, visit Cell-Free Assembly of Nanolipoprotein Particles (IL-11841, https://ipo.llnl.gov/technologies/life-sciences-biotech-and-healthcare/cell-free-assembly-nanolipoprotein-particles). 

Advantages/Benefits: 

• Faster manufacturing of engineered autologous T-cells for cancer immunotherapy
• High efficiency of protein delivery as compared to viral vector-based transfection method
• No risk of genomic DNA integration and therefore cancer
• Rapid response to evolving virus pathogens in controlling pandemics

Potential Applications: 

• Design, and biochemical study of CAR proteins
• CAR-T cell biology
• Immunotherapy of cancer

Development Status: 

Current stage of technology development:  TRL2

LLNL has filed for patent protection on this invention.

LLNL is seeking industry partners with a demonstrated ability to bring such inventions to the market. Moving critical technology beyond the Laboratory to the commercial world helps our licensees gain a competitive edge in the marketplace. All licensing activities are conducted under policies relating to the strict nondisclosure of company proprietary information. 

Please visit the IPO website at https://ipo.llnl.gov/resources for more information on working with LLNL and the industrial partnering and technology transfer process.

Note:  THIS IS NOT A PROCUREMENT.  Companies interested in commercializing LLNL's “protein mediated immune cell engineering” should provide an electronic OR written statement of interest, which includes the following:

1. Company Name and address.
2. The name, address, and telephone number of a point of contact.
3. A description of corporate expertise and/or facilities relevant to commercializing this technology.

Please provide a complete electronic OR written statement to ensure consideration of your interest in LLNL's “protein mediated immune cell engineering” technology.

The subject heading in an email response should include the Notice ID and/or the title of LLNL’s Technology/Business Opportunity and directed to the Primary and Secondary Point of Contacts listed below.

Written responses should be directed to:

Lawrence Livermore National Laboratory

Innovation and Partnerships Office

P.O. Box 808, L-779

Livermore, CA  94551-0808

Attention:   IL-13908