Lentiviral Technologies for Cell Therapy
Lentiviral vectors integrate stably into the genome and are thus a reliable tool for ex vivo gene therapy or cell therapy. SIRION offers different technologies for cell therapy developers:
Lentivirus Surface Modification Technology
Increasing specificity is a key prerequisite for developing safe and effective gene and cell therapies. Our surface modification technology directs lentiviral vectors against a specific molecular target to further improve transduction efficiencies. The technology can be used for optimizing gene transfer to specific cell types such as CD8 cells. Due to its universal applicability and non-toxic chemistry, targeting of various cell types is feasible.
The key element of the surface modification is the display of a targeting ligand such as scFv antibody fragments on the virus envelope. These single-chain antibody fragments have a high affinity and specificity to peripheral proteins of cell surfaces, enabling precise viral transduction.
SIRION Biotech’s lentivirus surface modification technology has several advantages:
Achievement of sufficient genetic modification at low MOIs
Effective independent of cell type
Synergistic effect with LentiBOOST (see figure)
Ideal for treating otherwise hard to transduce, therapeutically relevant cell types.
Figure 2. Lentivirus surface modification technology: 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® and retargeted scFv-CD30 VSV-G lentivirus.
1. Höfig et al.,Poloxamer synperonic F108 improves cellular transduction with lentiviral vectors. J. Gene Med. 14:549-60 (2012)
2. Höfig et al.,Systematic improvement oflentivirus transduction protocols by antibody fragments fused to VSV-G as envelope glycoprotein. J. Biomaterials (2014)
Therapeutic Expression Cassette Development
The lentiviral vector plasmid backbone and optimized therapeutic transgene expression cassette are the basis for successful lead vector design for CGT development.
Lentiviral vectors feature a high packaging capacity for large and complex transgene cassettes and are an excellent vehicle for CAR and TCR constructs in ex vivo gene therapy development. Our lentivirus specialists provide intensive analysis of transgene cassettes and are trained to support CGT developers in identifying the best design for the targeted application by optimizing safety, efficacy and manufacturability. Cell immunotherapy products are particularly affected by the tumor environment and require additional strategies to enhance persistence and retain functionality.
For our development process, we apply a DESIGN -BUILD-TEST- LEARN framework, which involves:
DESIGN a vector candidate library in-silico
BUILD the manufacturing and characterization of the vector candidates and respective particles
TEST the readout of the transgene functionality and particle performance to identify the most favorable vector design
LEARN by generating data on lead vector performance and feeding new insights into subsequent development cycles where necessary
To tailor the therapeutic transgene cassette to the CGT developer’s needs, a broad range of strategies and molecular tools is offered, including:
Physiologic and regulated promoter activity
Reduction of immunogenicity (e.g. by CpG analysis)
Tissue specific translation regulation
Transcriptional and translational regulation of bi- and multicistronic cassettes
SIRION Biotech actively collaborates with leading research groups and industrial partners to expand our expertise, e.g. by developing novel CAR designs or tissue specific transgene expression. Our specialists are also active members of well-known national and international CGT societies to strengthen the connection to leading scientists and KOLs worldwide.
Lentiviral Vector Backbones Optimized for Clinical Use
SIRION optimized lentiviral vector backbones for clinical use to shuttle the therapeutic transgene safely and efficiently into the patient genome. The development of these backbones is guided by three principles:
Decrease the amount of viral sequences transferred into the genome of the patient,
Improve the manufacturability of the lentiviral particles,
Improve the manufacturing process of an ex vivo gene therapy.
Our lentiviral vector backbone 1.0 is optimized for clinical application. Since all necessary elements of plasmid and lentiviral backbone are already established, cell therapy developers can focus on therapeutic transgene design. SIRION Biotech optimized lentiviral vector backbone 1.0 is already used in pre-clinical and clinical programs for cell therapy (e.g., CAR-T and TCR).
Cell therapy developers can access SIRION‘s clinically optimized lentiviral vector backbones or use our capabilities for customized de novo development of a novel lentiviral vector backbone. SIRION also provides support with backbone documentation for sequence and plasmid material traceability to smooth the path for IND applications.
If you are interested in our lentiviral vector backbones optimized for clinical use, please get in touch with us via our contact form.
SIRION Biotech’s proprietary manufacturing processes are optimized for minimal process- and product related impurities for research and preclinical studies.
Manufacturing of lentiviral particles for research is following our ISO certified standard quality manufacturing procedure. For pre-clinical and clinical projects, USP and DSP can be adapted to meet client-specified quality attributes.
We ensure minimized impurities, that are:
- Process related
- Transfection derived
- Cell medium derived
- Host cell derived
- Purification derived.
We offer a broad range of extended QCs to monitor and document purity, potency, safety and identity of the lentiviral plasmid backbone, therapeutic transgene cassette, and manufactured lentiviral particles. The manufacturing procedures, QCs and documentation is specific to the project and tailored to the exact requirements of each CGT developer.
Potential Drug substance blueprints and developed processes can be transferred to our worldwide CDMO network for efficient GMP manufacture set up. The streamlined transfer of manufacturing and QC procedures from SIRION to a GMP setting is coordinated by our GMP Alliances team.
Contact us today to accelerate your cell therapy development.
LentiBOOST Transduction Enhancer
LentiBOOST® is a highly effective, non-cytotoxic transduction enhancer for clinical applications using lentiviral vectors. It acts as a universal receptor-independent adjuvant and facilitates fusion of lentivirus with the cell membrane.
LentiBOOST increases vector copy number and significantly improves lentivirus transduction efficiency at reduced MOIs. It is ideal for clinical transduction protocols for ex vivo stem cell-based gene therapies and CAR-T cell therapies.
LentiBOOST is available as either pharma grade or GMP grade material. The GMP-grade reagent is currently used in more than 30 clinical trials worldwide and is well known to regulatory authorities.
LentiBOOST technology can be applied to a wide range of clinically relevant cell types:
CD34+ hematopoietic stem cells (HSC)
Mesenchymal stem cells (MSC)
Neuronal progenitor cells
Primary T cells and hard-to-transduce murine T cells
And many more
We offer different licensing models for academic institutions and industry partners. For more information, please contact our Business Development and Licensing team at: firstname.lastname@example.org or use our contact form.