Cell Therapy (Ex-vivo Gene Therapy)
Efficient Transduction and Gene Expression – Improving Clinical Trials
Developing modern cell therapies necessitates exact control of gene expression.
The SIRION technology platform offers versatile options to identify and optimize the best possible approach for your preclinical and therapeutic R&D.
LentiBOOST™ – Improve Transduction of Hematopoietic Cells
LentiBOOST® is a highly effective, non-cytotoxic transduction enhancer for preclinical and clinical application of lentiviral vectors. It is a universal polaxamer-based, receptor-independent adjuvant which facilitates fusion of lenitivrus particles with cell membrane, significantly increasing transduction efficiency.
LentiBOOST® can be applied to a wide range of clinically relevant cell types including CD34+ hematopoietic stem cells (HSCs), primary T cells, NK cells, fibroblasts, and hard-to-transduce murine T cells. These unique features make it a promising candidate to improve clinical transduction protocols for ex vivo gene therapies and CAR-T cell therapies.
In the demonstration above, LentiBOOST™ increases transduction by a factor of 5.
LentiBOOST™ Pharma grade
For use in preclinical research and process development only. For quotes and further requests on this technology, please inquire with lentiboost@sirion-biotech.com.
LentiBOOST™ GMP grade
For use in clinical stage protocols. Currently included in more than 20 Phase III and I/II clinical trials in the US and in Europe. Licensing options for Clinical/Commercial Use and Development are available.
Please inquire with licensing@sirion-biotech.com.
Benefits for Drug Development at a glance
Improved lentiviral transduction efficiency, up to 90%.
⇒ Increased expression levels of therapeutic protein have a favorable effect on success rates of clinical trials.
Positive impact on cell proliferation for CD34+ and T cells.
⇒ Reduced cost of goods, optimized and stable transgenic cell manufacturing.
Titratable vector copy numbers per cell.
⇒ Strong and durable therapeutic protein expression, in line with FDA/EMA criteria for ATMPs production.
Successful track record of integration into clinical trials (III and I/II) in the US and Europe.
⇒ Proven lack of cell toxicity and prior clinical applications expedite IND filing.
GMP grade batches available.
⇒ With all necessary documentation for direct integration into clinical programs.
Read about LentiBOOST™ in the news.
Contact us to discover how this adjuvant can excel your program: lentiboost@sirion-biotech.com.
LentiTHERAPY™ – Cell Specific Transduction Technology
The LentiTherapy™ 3 hit strategy to target therapeutically relevant cell types
Step 1: Retargeting antibody fragments on the virus envelope. These single-chain antibody fragments have a high affinity and specificity to peripheral proteins of cell surfaces, allowing targeted precision of viral transduction.
Step 2: LentiBOOST™ transduction enhancer increases the permeability of cell membranes, allowing lentiviruses easy access. The chemical basis for LentiBOOST™ is non-toxic and is used as a standard component in pharmaceutical pill formulation. This unique transduction enhancer is especially potent when used on non-adherent cells such as B-cell and T-cell transduction.
Step 3: Spinoculation increases the number of virus particles binding to the cells through centrifugal inoculation, enhancing the effectiveness of LentiBOOST™ and the retargeted envelope even further.
Due to its non-toxicity, the process is well suited for basic research as well as early clinical applications. LentiTherapy™ achieves sufficient genetic modification at low MOIs (less or equal to 1).
The figures show transduction experiments in KARPAS-299, SUP-M2 and SUDHL-1 cell lines incubated at MOI 10 or with copGFP-coding lentiviral particles +/- a spinoculation protocol, LentiBOOST (TM) and retargeted scFv-CD30 VSV-G lentivirus.
LentiTherapy™ is effective independent of cell type. The steps of this system influence each other synergistically, as demonstrated in the figure above. The treatment is effective at different MOIs and ideal for treating otherwise hard to transduce,therapeutically relevant cell types.
The LentiBOOST™transduction enhancer has been reported by collaborators from the academic sciences at the NYU Langone Medical Center to increase T-cell transduction significantly.
SIRION Biotech is searching for collaboration partners to help actively develop the application of the LentiTherapy™ Systemin pre-clinical and early clinical stages.
Publications
Höfig et al.,Poloxamer synperonic F108improves cellular transduction with lentiviral vectors. J. Gene Med. 14:549-60 (2012)
Höfig et al.,Systematic improvement oflentivirus transduction protocols by antibodyfragments fused to VSV-G as envelope glycoprotein. J. Biomaterials(2014)
Contact us – Discover how SIRION can help you reach your gene therapy goals.