Immunotherapy, which harnesses the natural power of the immune system to combat disease, presents a unique and transformative opportunity in biomedical research. This potential has been tapped into by various fields, particularly cancer research, leading to significant breakthroughs and clinical successes.
The immunotherapy landscape is rich and diverse, with strategies including cytokine-based interventions, antibody treatments, and adoptive cell therapies (ACTs). Each of these approaches holds considerable promise for revolutionizing the way we treat a wide range of diseases.
ACT modalities, including chimeric antigen receptor (CAR) T cells, tumor-infiltrating lymphocytes, and engineered T cell receptor (TCR)-based therapies, focus on enhancing or redirecting a patient's own immune cells, such as T cells, to recognize and attack diseased cells more effectively.
A crucial step in the development of ACTs is the genetic modification of immune cells—a process that involves altering the genetic material of these cells to equip them with new capabilities or improve their existing functions. Lentiviral vectors
One widely adopted method involves the use of lentiviral vectors, which are known for their efficiency in integrating therapeutic genes into target cell genomes. Lentiviral vectors offer several advantageous traits, including:
- Efficient gene delivery in both dividing and non-dividing cells
- Large cargo capacity for complex genetic modifications
- Integration into the host cell genome, leading to long-term expression of the introduced genes
- Relatively low immunogenicity
Why enhance lentiviral transduction?
Researchers are continually seeking innovative ways to optimize the efficiency of lentiviral transduction. High transduction efficiency is crucial for the success of ACTs as it directly impacts the effectiveness, scalability, and manufacturing cost of these therapies.
Effectiveness: A higher percentage of successfully modified immune cells can translate to a more potent therapeutic product.
Scalability: More efficient transduction means more cells are successfully modified with fewer resources and varying qualities of patient cells can be counterbalanced, enabling larger-scale production.
Cost: Efficient transduction reduces the amount of patient cells and viral vector required, lowering production costs.
LentiBOOST™ technology for enhancing transduction
Revvity’s LentiBOOST™ technology is an enhancer designed to improve lentiviral transduction, particularly in difficult-to-transduce human and other mammalian cells. LentiBOOST technology works by facilitating viral entry into target cells, increasing the likelihood of successful gene delivery and expression by enhancing transduction efficiency and VCN.
The adoption of LentiBOOST technology in T cell research and advanced T cell therapy development has been growing rapidly, with studies demonstrating its efficacy in:
- Optimizing allogeneic CAR-T cell production1
- Enhancing CAR-Treg transduction2
- Facilitating the creation of dual-targeting CAR-T cells3
- Improving TCR gene delivery in various T cells4
The growing body of research supporting LentiBOOST technology's efficacy showcases its potential to accelerate next-generation cell therapies.
To learn more about the applications and future potential of the LentiBOOST technology in T cell research and therapeutic development, download our latest literature review: “Empowering T cell therapies: the strategic use of LentiBOOST™ in CAR-T and TCR modalities.”
LentiBOOST Pharma-Grade: For research use only. Not for use in diagnostic procedures.
LentiBOOST GMP-Grade: Not for diagnostic use. Other applications must be authorized by a license from Revvity.
References
- Kim-Hoehamer Y-I, Riberdy JM, Zheng F, Park JJ, Shang N, Métais J-Y, et al. Development of a cGMP-compliant process to manufacture donor-derived, CD45RA-depleted memory CD19-CAR T cells. Gene Therapy. 2022 Jan 8;30(3–4):222–31. doi:10.1038/s41434-021-00307-0
- Lamarthée B, Marchal A, Charbonnier S, Blein T, Leon J, Martin E, et al. Transient mTOR inhibition rescues 4-1BB CAR-Tregs from tonic signal-induced dysfunction. Nature Communications. 2021 Nov 8;12(1). doi:10.1038/s41467-021-26844-1
- Lee LS, Lim WC, Mactier C, Dias Alves Pinto J, Pereira V, Vaughan M, et al. Development of a phase 1 study evaluating the activity of modular CAR T for multiple myeloma (MCARTY) targeting BCMA and CD19 for improved persistence. Blood. 2023 Nov 2;142(Supplement 1):350–350. doi:10.1182/blood-2023-185085
- Lo Presti V, Cornel AM, Plantinga M, Dünnebach E, Kuball J, Boelens JJ, et al. Efficient lentiviral transduction method to gene modify cord blood CD8+ T cells for cancer therapy applications.