Although anti-cancer therapies via pharmaceutical approaches have seen much improvement in the last several decades, the high recurrence rate of malignancy remains an unsolved problem. As the therapies continue to evolve, a new class of cell-based therapeutics has emerged, with autologous CAR-T cells leading the field and driving unprecedented outcomes in patients with relapsed/refractory malignancies. Natural Killer (NK) cells, given their intrinsic abilities to identify and kill tumor cells, have become an attractive source for anti-cancer cell therapy. In comparison to CAR-T cells, the application of CAR-NK is reported to have a number of additional benefits.
• Large doses of T cells can induce cytokine release syndrome (CRS). NK cells have a distinct cytokine release profile which reduces the occurrence of CRS and therefore strengthens the safety of use.
• Whereas CAR-T cells will mostly kill target cells by a CAR-specific mechanism, CAR-NK cells can leverage NK-cell-intrinsic cytotoxicity mechanisms to induce target cell death. This boosts the killing effect and may help to maintain an anti-tumor response even when target cells down-regulate specific antigens in both CAR-dependent and CAR-independent manners.
• Allogeneic-grafted CAR-NK cells have a profound killing effect. These cells hold great potential to become an ‘’off-the-shelf product’’, as therapeutic manufacturers can obtain potent NK cells from healthy donors, thus expanding the material availability for cell therapy manufacturing. Additionally, clinical evidence has shown that CAR-NK cells present a low risk of inducing graft-versus-host-disease.
• Based on current regulations, CAR-NK infusions do not require hospitalization due to the low potential toxicity, reducing the high clinical costs associated with cell therapy administration.
However, the pursuit of high-quality, clinical-grade manufacturing consumes excessive resources. An automated cell therapy production platform can help reduce the production cost and hence make the therapy more accessible to the public. Further, there are more advantages to implementing automated cell production:
• Parameters in an automation system are traceable: a fundamental requirement in a GMP environment.
• Automation reduces the requirement for a highly-trained workforce and supports protocol reproducibility.
• Implementation of automation at early stage supports smooth scalability during and after regulatory approval.
• Potential for reducing overall project cost through streamlined development.
Though much progress has been made, the application of CAR-NK cell therapy is still at an early stage. In spite of encouraging news from ongoing clinical trials for both hematological and solid tumors, further investigations are required to complete the safety profile for individual CAR-NK cell therapies. As CAR-NK therapies continue to progress through clinical development, choosing an automated manufacturing platform can help reduce the complexity of these processes. Utilizing best-in-class automation instrumentation to link individual closed manufacturing processes is one option for facilitating the expansion of clinical manufacturing. The Cocoon® Platform from Lonza, for example, can be a reliable choice for production for emerging immunotherapies, such as CAR-NK cells. This automated, functionally closed system can reduce hands-on requirements for cell isolation, activation, genetic modification (transduction or transfection) and expansion of cells.
Written by Ming, Scientific Support Specialist, together with Tamara and Peter from the Personalized Medicine team
References:
Khawar MB, Sun H. CAR-NK Cells: From Natural Basis to Design for Kill. Front Immunol. 2021 Dec 14;12:707542.doi: 10.3389/fimmu.2021.707542. PMID: 34970253; PMCID: PMC8712563.
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