Creating personalized treatments based on each patient’s individual cancer diagnosis has been shown to be a powerful tool in the fight against cancer. Non-viral electroporation is emerging as the method of choice for gene editing of harvested immune cells, as reported in a recent study published in Nature and discussed by Thermo Fisher Scientific’s collaborator, PACT Pharma. Non-viral electroporation has demonstrated efficacy, safety benefits, and flexibility, and allows for the use of a variety of payloads to be introduced into a target cell of choice, including use of CRISPR-Cas9 gene editing tools.
Nature publication: Non-viral precision T cell receptor replacement for personalized cell therapy
In a new study on Nature.com, researchers have conducted a first-in-human phase I clinical trial, utilizing T cell receptor-engineered T cells that target intracellular tumor neoantigens.
“T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells. Here we developed a clinical-grade approach based on CRISPR–Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes…This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.”
“The ultimate goal of any cancer therapy is to target and kill cancer cells while sparing normal cells. The human immune system is suited to achieve this goal owing to the specificity of TCRs.” Foy, S.P., Jacoby, K., Bota, D.A. et al. Non-viral precision T cell receptor replacement for personalized cell therapy. Nature 615, 687–696 (2023). https://doi.org/10.1038/s41586-022-05531-1
PACT Pharma’s first and only in-human personalized neoTCR adoptive cell therapy
Non-viral gene editing has enabled PACT Pharma to have the first and only in-human personalized neoTCR adoptive cell therapy in the clinic.
PACT’s single-step non-viral precision genome engineering technology can knock-out, knock-down, knock-in, and precisely regulate additional genes in a single step. These modifications have the potential to expand the applicability of drug products and are broadly applicable to a variety of other cellular therapies and research models.
PACT is developing an adoptive therapy that aims to create curative therapies tailored to each individual patient. Every patient’s cancer is personal and unique, with highly specific mutations.
New technologies enable safety and performance at scale
The need for standardization and high manufacturing success rates are critical drivers of innovation in cell therapy. Thermo Fisher Scientific has built a fit-for-purpose portfolio of modular instrumentation platforms designed to support closed, large-scale cell therapy manufacturing — enabling automation of the end-to-end manufacturing workflow.
Click to see the full size infographic. Source: https://cdn.insights.bio/uploads/attachments/C_TFB_202NT.pdf
The Gibco CTS DynaCellect Magnetic Separation System is a closed and automated system for consistent cell isolation/activation and bead removal. Following the isolation and bead removal process using the CTS DynaCellect system, the next step in the process is cell engineering. Leveraging non-viral technologies such as electroporation for cell engineering addresses common limitations of viral-based systems and has shown promise for developing personalized cell therapies. Thermo Fisher Scientific’s CTS Xenon Electroporation System is designed to provide the safety and performance profile required at scale.
Watch the webinar to see how these technologies support the enhancement of cancer therapies.