Abstract
Immunotherapy is a very promising therapeutic approach against cancer that is particularly effective when combined with gene therapy. Immuno-gene therapy approaches have led to the approval of four advanced therapy medicinal products (ATMPs) for the treatment of p53-deficient tumors (Gendicine and Imlygic), refractory acute lymphoblastic leukemia (Kymriah) and large B-cell lymphomas (Yescarta). In spite of these remarkable successes, immunotherapy is still associated with severe side effects for CD19+ malignancies and is inefficient for solid tumors. Controlling transgene expression through an externally administered inductor is envisioned as a potent strategy to improve safety and efficacy of immunotherapy. The aim is to develop smart immunogene therapy-based-ATMPs, which can be controlled by the addition of innocuous drugs or agents, allowing the clinicians to manage the intensity and durability of the therapy. In the present manuscript, we will review the different inducible, versatile and externally controlled gene delivery systems that have been developed and their applications to the field of immunotherapy. We will highlight the advantages and disadvantages of each system and their potential applications in clinics.
Highlights
Immunotherapy has drastically evolved since the past 30 years, providing diverse approaches for boosting the intrinsic power of the host’s immune system to target different diseases, especially cancer
Radiation systems should be further improved in order to achieve minimal basal activity if considered for other clinical applications or methods of administration and obtain moresensitive promoters, 10 Gy dose is relatively high for radiotherapy [122]
We have focused on inducible systems that meet four characteristics: [1] the expression of the transgene can be externally-controlled, [2] they are reversible systems, they can be turn on and off multiple times
Summary
Immunotherapy has drastically evolved since the past 30 years, providing diverse approaches for boosting the intrinsic power of the host’s immune system to target different diseases, especially cancer. Multiple inducible systems have been developed, we will focus on those that are externally controlled, are able to regulate any transgene and are potentially applicable to humans.
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