Autologous chimeric antigen receptor T‐cell (CAR‐T) therapies have garnered unprecedented clinical success with multiple regulatory approvals for the treatment of various hematological malignancies. However, there are still several clinical challenges that limit their broad utilization for aggressive disease conditions. To address some of these challenges, allogeneic cell therapies are evaluated as an alternative approach. As compared with autologous products, they offer several advantages, such as a more standardized “off the shelf” product, reduced manufacturing complexity, and no requirement of bridging therapy. As with autologous CAR‐T therapies, allogeneic cell therapies also present clinical pharmacology challenges due to their in vivo living nature, unique pharmacokinetics or cellular kinetics (CKs), and complex dose‐exposure‐response relationships that are impacted by various patient‐ and product‐related factors. On top of that, allogeneic cell therapies present additional unique challenges, including attenuated in vivo persistence and graft‐vs.‐host disease risk as compared with autologous counterparts. This review draws comparison between autologous and allogeneic cell therapies, summarizing key engineering aspects unique to allogeneic cell therapy. Clinical pharmacology learnings from emerging clinical data of allogeneic cell therapy programs are also highlighted, with particular emphasis on CK, dose‐exposure‐response relationship, lymphodepletion regimen, repeat dosing, and patient‐ and product‐related factors that can impact CK and patient outcomes. There are specific unique challenges and opportunities arising from the development of allogeneic cell therapies, especially in optimizing lymphodepletion and establishing a regimen for repeat dosing. This review highlights how clinical pharmacologists are well positioned to help address these challenges by leveraging novel clinical pharmacology and modeling and simulation approaches.

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“现成”同种异体细胞疗法的临床药理学考虑因素

自体嵌合抗原受体 T 细胞 (CAR-T) 疗法取得了前所未有的临床成功，并获得多项监管批准，可用于治疗各种血液恶性肿瘤。然而，仍然存在一些临床挑战限制其在侵袭性疾病中的广泛应用。为了解决其中一些挑战，同种异体细胞疗法被评估为一种替代方法。与自体产品相比，它们具有多种优势，例如更标准化的“现成”产品、降低的制造复杂性以及不需要桥接治疗。与自体 CAR-T 疗法一样，同种异体细胞疗法也面临临床药理学挑战，因为它们具有体内活性、独特的药代动力学或细胞动力学 (CK) 以及受各种患者和产品影响的复杂的剂量-暴露-反应关系相关因素。最重要的是，同种异体细胞疗法提出了额外的独特挑战，包括与自体细胞疗法相比，体内持久性减弱和移植物抗宿主疾病风险。这篇综述对自体细胞疗法和同种异体细胞疗法进行了比较，总结了同种异体细胞疗法独特的关键工程方面。还强调了从同种异体细胞治疗项目的新兴临床数据中获得的临床药理学知识，特别强调 CK、剂量-暴露-反应关系、淋巴清除方案、重复给药以及可能影响 CK 和患者结果的患者和产品相关因素。同种异体细胞疗法的发展带来了特定的独特挑战和机遇，特别是在优化淋巴细胞清除和建立重复给药方案方面。这篇综述强调了临床药理学家如何利用新颖的临床药理学以及建模和模拟方法来帮助应对这些挑战。