Gene and Cell Therapy Unit, Genomic Medicine Department, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada, Spain.
LentiStem Biotech, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada, Spain.
Front Immunol. 2020 Sep 4;11:2044. doi: 10.3389/fimmu.2020.02044. eCollection 2020.
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.
免疫疗法是一种非常有前途的癌症治疗方法，当与基因疗法结合使用时尤其有效。免疫基因治疗方法已经导致了四种先进治疗药物产品（ATMPs）的批准，用于治疗 p53 缺陷型肿瘤（Gendicine 和 Imlygic）、难治性急性淋巴细胞白血病（Kymriah）和大 B 细胞淋巴瘤（Yescarta）。尽管取得了这些显著的成功，但免疫疗法仍然与 CD19+恶性肿瘤的严重副作用有关，并且对实体瘤效率低下。通过外部给予诱导剂来控制转基因表达被认为是提高免疫疗法安全性和疗效的一种有效策略。目的是开发基于智能免疫基因治疗的 ATMPs，可以通过添加无害的药物或试剂来控制，使临床医生能够控制治疗的强度和持久性。在本文中，我们将回顾已经开发的不同的诱导型、多功能和外部控制的基因传递系统及其在免疫治疗领域的应用。我们将强调每个系统的优缺点及其在临床上的潜在应用。
