Applications > Cell Therapy > Immunotherapy
A powerful approach to cancer therapy involves modifying the patient's immune cells or cancer cells in order to enhance the immune response against them. Such modifications may be accomplished by inserting appropriate genetic information or antigen into the cells. The safety and efficiency of such a procedure depends in large part upon the method chosen for gene delivery into the cancer cells. The shortcomings of available technologies to deliver genetic information to target immune or cells has prompted leading academic translational medical centers and commercial partners to use MaxCyte flow electroporation gene delivery technology. MaxCyte technology is ideal for migrating potential cellular immune therapeutics from bench-top development to the clinic with increased therapeutic potency, lower costs and greatly reduced development time.
Features:
- Bench to clinic scalability
- Cell loading flexibility
- Nucleic acids including mRNA, siRNA and DNA
- Proteins including tumor lysate
- Diverse cell compatibility
- Cell lines
- Primary cells including mature dendritic cells
- Safety
- Simple methodology using no additional chemical or biological reagents
- FDA Master File
Figure 1 – High Efficiency Protein Loading
MaxCyte flow electroporation can be used to load cells not only with various nucleic acids, but also with proteins (Figure 1) including tumor lysates. This feature allows patient immune cells, such as dendritic cells, to be loaded with tissue lysates which act as cancer vaccines when re-infused into patients. Electroporation by itself does not lead to any appreciable loss in dendritic cell viability, phenotype or T cell activation function (1,2). MaxCyte technology loading of cells with DNA, mRNA or protein antigens results in increased antigen uptake compared to co-incubation control. The amount of antigen loading can be controlled to deliver optimal concentration of processed antigenpeptide complex presentation in functionally mature DC resulting in enhanced T cell activation and anti-tumor efficacy(3).
Figure 2 – mRNA T-cell Engineering
Additionally, cells of the immune system can be isolated and engineered for specific functions or expression of antigens and re-introduced into the patient. Figure 2 is an example of engineering T-cells with mRNA encoding the chimeric antigen receptor (CAR) with the goal of creating cells with increased anti-tumor activity(4). High viability and efficiency of CAR molecules was observed over multiple days following mRNA loading. CAR-engineered cells exhibited enhanced anti-tumor activity compared with conventional, non-engineered cells and redirected cytolytic responses toward tumor cells expressing antigens encoded by the CAR molecule.
References
1. Weiss JM, et.al. Cancer Gene Ther. 2004 May;11(5):346-53.
2. Liu LN, et.al. Methods Mol Biol. 2008;423:139-53.
3. Weiss JM, et.al. J Immunother. 2005 Nov-Dec;28(6):542-50.
4. Li LH, et.al. Poster #3894, Tumor Immunotherapy Session II, American Society of Hematology Annual Meeting, Dec 2008.