One of the most significant innovations in personalized cancer medicine over the past decade has been the development of chimeric antigen receptor (CAR) T-cell therapy, in which a patient’s own cells are engineered to becoming cancer-fighting weapons (Figure 1). Blending oncology, biotechnology, and immunology, CAR T-cell therapy has revolutionized the management of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), various B-cell non-Hodgkin’s lymphomas (NHLs), and multiple myeloma (MM). Since 2017, there have been six CAR T-cell therapies that have been approved by the US Food and Drug Administration (FDA) for relapsed/refractory hematological malignancies. These include four products targeting CD19 for the treatment of B-cell NHL and B-ALL (tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, and lisocabtagene maraleucel) and two products targeting B-cell maturation antigen (BCMA) for MM (idecabtagene vicleucel and ciltacabtagene autoleucel). To date, all approved CAR T-cell therapies have been autologous products (i.e., engineered using the patient’s own T-cells); however, development of “off-the-shelf” allogeneic products (derived from donors), including allogeneic CAR NK products is underway. As the field has grappled to optimize the CAR constructs, prolong duration of response, and minimize toxicities, such as cytokine release syndrome (CRS) and neurotoxicity,¹ it has been fascinating to observe how the principles of quantitative clinical pharmacology are being adapted and applied to understand the behaviors of a living drug. For example, a general model of in vivo cellular kinetics (CKs) of CAR T-cells has been proposed that involves initial rapid distribution following infusion, then subsequent expansion followed by biexponential decline.²

In this issue of Clinical Pharmacology & Therapeutics (CPT) Ogasawara and colleagues contribute to the growing understanding of the relationship between in vivo CAR T-cell expansion, antitumor efficacy, and toxicity.³ The CKs of lisocabtagene maraleucel from patients treated in the TRANSCEND NHL 001 trial⁴ were evaluated using two bioanalytical methods: quantitative polymerase chain reaction to measure the transgene and flow cytometric detection of the nonfunctional truncated epidermal growth factor receptor that is co-expressed along with the CD19-specific CAR from peripheral blood samples.³ Reported CK parameters included maximum expansion (C_max), time to C_max (T_max), and area under the curve (AUC) for both 0–28 and 0–90 days post-infusion (AUC_0–28 days and AUC_0–90 days). A high correlation between AUC_0–28 days and C_max or AUC_0–90 days was observed. Multivariable logistic regression analysis revealed an association between in vivo cellular expansion and both antitumor efficacy (overall response and complete response rates) and toxicity (CRS and neurologic events). This analysis further demonstrated that patient age and tumor burden were confounding variables. Of particular interest were the data obtained from patients who received a second infusion of the product, either as part of a planned two-dose schedule or as salvage therapy at the time of relapse. These studies revealed that the planned second dose administered on day 15 did not result in a higher C_max, whereas those who received a second infusion at the time of relapse achieved C_max/AUC_0–28 days values that were either equivalent or lower than what had been achieved after the initial infusion.

This work adds to the findings from other CAR T-cell trials that have explored potential dose/exposure-response relationships from the perspective of in vivo expansion and CKs. A CK analysis from patients treated on the JULIET study (tisagenlecleucel in diffuse large B-cell lymphoma), showed no difference in CK parameters between responders and nonresponders; although, there was a trend toward higher-than-median C_max being associated with longer duration of response.⁵ However, there was an association between higher C_max (or AUC_0–28 days) and rates of grade 3/4 CRS.⁵ Similar studies with tisagenlecleucel in patients with B-ALL or chronic lymphocytic leukemia (CLL) demonstrated an association between C_max/AUC and response.^{6, 7} Expansion of axicabtagene ciloleucel in patients with B-NHL was associated with response and neurological events but not CRS.⁸ In the MM setting, idecabtagene vicleucel C_max was associated with deeper response and longer progression free survival (PFS).⁹ As 97% of patients with MM receiving ciltacabtagene autoleucel achieved a response, any potential correlation between expansion and response was not possible to discern; although, there appeared to be an association between expansion and severity of CRS.¹⁰ A commonality among all of these studies is high interpatient variability. Less information is available regarding the kinetics of long-term persistence of various CAR T-cell products as well as the kinetics in other relevant compartments, such as the bone marrow, secondary lymphoid tissues, and cerebral spinal fluid.

Although a relationship between cell dose administered and response has been demonstrated, this is generally limited to responses being dependent on a certain dose threshold, and above that threshold dose-dependency is not consistently seen.^{9, 11-14} In addition, consistent correlations between dose administered and subsequent expansion have not been observed.^{3, 12, 13} In a previously published population CK analysis of lisocabtagene maraleucel, a discernible dose-exposure relationship for cellular expansion could not be observed in the tested administered dose range of 44–156 × 10⁶ CAR T-cells.¹⁵ Indeed, the inability to discern dose-exposure relationships with CAR-T therapy is reconciled well in simulations from systems pharmacology models¹⁶ as well as mechanism-informed modeling of clinical CK of multiple CAR-T products.¹⁷ The interpretation of the results of exposure-response analyses for cell therapies like lisocabtagene maraleucel may thus not be entirely analogous to that applicable for small molecules or biologics. Whereas the multivariable exposure-response relationships described by Ogasawara et al.³ advance our understanding of the importance of CAR-T expansion on clinical outcomes in the context of other sources of variability, quantitative translation to dose selection decisions may not be straightforward. Typically, the purpose of an exposure-response analysis conducted as part of a clinical pharmacology plan in drug development is to quantify the relationship between the systemic exposure of a therapeutic and the associated clinical outcomes (efficacy or toxicity). Together with an understanding of the dose-exposure relationship and associated intrinsic and extrinsic sources of variability in systemic exposures, the desired therapeutic dose range can be inferred and tailored as appropriate across populations and clinical contexts of use. Given that the inability to discern dose-exposure relationships is not uncommon with CAR-T therapies owing to far greater contribution of biological variability to CAR-T expansion than the administered dose, clinical pharmacologists will need to rethink strategies for informing dose optimization. This will require continued evaluation of the translational fidelity of systems pharmacology models as such models should in principle help explain and extend inference from clinically observed exposure-response relationships to optimize CAR-T precision therapy. Additional challenges with pharmacometric analyses of exposure-response relationships for CAR-T therapies include the need to carefully consider the impact of immortal time bias¹⁸ when dealing with efficacy end points like duration of response or overall survival. Although less of a concern when using early “landmark” measures of cellular expansion as the exposure metric (e.g., AUC over 28 days following infusion) for relationships to response rates, these pharmacostatistical considerations are important if the question being asked involves the relationship of CAR-T persistence to response duration or survival outcomes in time-to-event analyses.

Ultimately the in vivo expansion of the CAR T-cell product appears to be just one of the factors that influences short- and/or long-term efficacy. Other potential contributors include the starting substrate, the phenotypes produced during the manufacturing process, pretreatment lymphodepletion regimens, the cell dose administered, the medications received after CAR T-cell administration, and the long-term persistence (and phenotype) of the engineered cells. From the starting substrate perspective, the collected T-cells may vary widely among individuals due to numbers and types of prior therapies, contributing to prolonged lymphopenia and/or suppressed T-cell function. For example, in the phase II study of idecabtagene vicleucel in patients with relapsed/refractory MM, the patient population had a median of six prior lines of therapy, with a range from 3 to 16 prior lines.⁹ Thus, the quality of the collected T-cells would be expected to be very heterogeneous. On a broader level, the relative numbers of transduced CD4+ and CD8+ T-cells may be of importance (and lisocabtagene maraleucel has separate manufacturing processes and infusions for CD4+ and CD8+ T-cells), but more sophisticated immunophenotyping may be more informative. In a study involving CAR T-cell therapy in patients with CLL, it was found that collected T-cells with a higher frequency of CD27+CD45RO-CD8+ T-cells had memory-like characteristics and were associated with sustained remission.¹⁹ Manipulation of the T-cells during manufacturing may elicit a superior phenotype, such as enrichment of memory-like T-cells and relative depletion of senescent cells. This approach is being evaluated with the bb21217 anti-BCMA product, which involves the use of ex vivo culture of the cells with a phosphoinositide 3-kinase inhibitor. Preliminary results from the ongoing phase I study of this product suggest that patients with higher than median number of CD8+ CAR T-cells expressing CD27/CD28 had significantly longer duration of response compared to patients with lower than median values (P = 0.0024).²⁰

As CAR T-cells represent a therapy that can replicate and sustain itself over time, an improved understanding of the mechanisms driving in vivo CAR T-cell expansion and persistence is needed. There has been much scrutiny over whether therapies administered to manage CAR T-cell-induced CRS can abrogate expansion and efficacy. In general, the literature to date has suggested that receipt of corticosteroid therapy post-CAR T-cell administration does not negatively impair in vivo expansion or efficacy; although, one study found that use of corticosteroid treatment within 7 days of CAR T-cell infusion was associated with shorter PFS.^21-24 In the population CK model of lisocabtagene maraleucel, treatment with tocilizumab and/or corticosteroids was identified as a covariate associated with a higher C_max and AUC_0-28 days.¹⁵ However, as these metrics of expansion were also associated with CRS or neurological events necessitating administration of tocilizumab and/or corticosteroids, the interpretation of causality in covariate analyses is not straightforward, and the authors ultimately concluded that the covariates did not have a meaningful impact on lisocabtagene maraleucel CKs.¹⁵ Whether other immunomodulatory agents (e.g., lenalidomide) can enhance the cytolytic activity and persistence of CAR T-cell therapy is currently under investigation. Finally, long-term follow-up (7 years) of 2 patients with CLL who received CD19 CAR T-cells demonstrated changes over time in the phenotypes of the T-cells as well as the numbers and identities of the clones that contributed to long-term CAR T-cell persistence.²⁵

Ogasawara et al.’s finding that a second administration of lisocabtagene maraleucel 2 weeks after the first dose did not alter C_max³ further highlights the differences between cellular therapy and traditional therapeutics and the need for more extensive exploration of the factors controlling in vivo expansion. Determining the mechanisms for tumor resistance to CAR T-cell therapy remains an active area of investigation and is likely multifactorial, related to problems with CAR T-cell persistence and/or long-term cytotoxic activity, the tumor microenvironment as well as tumor-intrinsic mechanisms, such as loss of antigen expression or aberrant apoptotic machinery.^{26, 27}

The science behind cellular therapy is continuing to rapidly evolve, leading to the development of novel approaches, such as dual-targeting CAR T-cells (including T-cells co-expressing different CARs vs. mixtures of different CAR T products), armored CAR T-cells (engineered to secrete cytokines or antibody-like proteins), allogeneic CAR T-cells, CAR-NK cells, regional delivery of CAR T-cells, and combining CAR T-cell therapy with chemotherapeutic or immunotherapeutic agents. The field of clinical pharmacology will face new challenges to fully delineate the pharmacokinetics, pharmacodynamics, and pharmacometrics as these novel approaches reach human testing. Whereas pharmacokinetics for cellular therapy has evolved into CK, it is evident that understanding exposure-response relationships will require more than simply counting how many engineered cells are present at any given timepoint post-infusion. The inherent complexity of T-cell biology coupled with alterations in CAR T-cell phenotypes following infusion will require sophisticated molecular and cellular interrogation strategies to capture the phenotypic and functional characteristics of these living drugs. Collaboration with immunologists, systems pharmacologists, data scientists, and others working on cellular therapy will be critical.

Innovative modalities, such as cell and gene therapies, are transforming the therapeutic landscape in oncology and other disease areas, resulting in a spectrum of novel treatment options. This requires clinical pharmacologists to adapt and develop new skill sets, knowledge, and expertise. CPT aspires to continue to develop as the pre-eminent destination journal for research and educational publications in this area. To that end, the journal plans to devote the September 2023 themed issue to “Clinical Pharmacology of Novel Therapeutic Modalities” and a Call for Papers will be issued in the coming months.

在过去十年中，个体化癌症医学最重要的创新之一是嵌合抗原受体 (CAR) T 细胞疗法的开发，其中患者自身的细胞被设计成抗癌武器（图 1）。结合肿瘤学、生物技术和免疫学，CAR T 细胞疗法彻底改变了复发/难治性 B 细胞急性淋巴细胞白血病 (B-ALL)、各种 B 细胞非霍奇金淋巴瘤 (NHL) 和多发性骨髓瘤 (MM) 的管理）。自 2017 年以来，已有六种 CAR T 细胞疗法获得美国食品和药物管理局（FDA）批准用于治疗复发/难治性血液系统恶性肿瘤。其中包括用于治疗 B 细胞 NHL 和 B-ALL 的四种靶向 CD19 的产品（tisagenlecleucel、axicabtagene ciloleucel、brexucabtagene autoleucel 和 lisocabtagene maraleucel）和两种针对 MM 的 B 细胞成熟抗原 (BCMA) 产品（idecabtagene vicleucel 和 ciltacabtagene自亮细胞）。迄今为止，所有获批的 CAR T 细胞疗法都是自体产品（即使用患者自身的 T 细胞进行工程改造）；然而，“现成的”同种异体产品（来自供体）的开发正在进行中，包括同种异体 CAR NK 产品。随着该领域努力优化 CAR 结构、延长反应持续时间并最大限度地减少毒性，例如细胞因子释放综合征 (CRS) 和神经毒性，¹观察定量临床药理学原理如何被改编和应用以了解活药物的行为是一件很有趣的事情。例如，已经提出了 CAR T 细胞的体内细胞动力学 (CKs) 的一般模型，该模型涉及输注后的初始快速分布，然后是随后的扩增，然后是双指数下降。²

在本期临床药理学和治疗学( CPT ) 中，Ogasawara 及其同事有助于加深对体内CAR T 细胞扩增、抗肿瘤功效和毒性之间关系的理解。^{3使用两种生物分析方法评估了 TRANSCEND NHL 001 试验4}中接受治疗的患者的利索卡布他根 maraleucel 的 CK ：定量聚合酶链反应测量转基因和流式细胞术检测非功能性截短表皮生长因子受体，该受体与来自外周血样本的 CD19 特异性 CAR。³报告的 CK 参数包括最大扩展（C _max)、达到 C _max的时间(T _max ) 和输注后 0-28 天和 0-90 天（AUC _{0-28 天和}AUC _{0-90 天}）的曲线下面积 (AUC )。_{观察到 AUC 0-28 天}与 C _max或 AUC _{0-90 天}之间的高度相关性。多变量逻辑回归分析揭示了体内之间的关联细胞扩增和抗肿瘤功效（总体反应率和完全反应率）和毒性（CRS 和神经系统事件）。该分析进一步表明，患者年龄和肿瘤负荷是混杂变量。特别令人感兴趣的是从接受第二次输注该产品的患者中获得的数据，无论是作为计划的两次给药方案的一部分，还是作为复发时的补救治疗。这些_研_ _{_} _ _{_} _初次输液后取得的成果。

这项工作增加了其他 CAR T 细胞试验的结果，这些试验从体内扩增和 CK的角度探索了潜在的剂量/暴露-反应关系。JULIET 研究（弥漫性大 B 细胞淋巴瘤中的 tisagenlecleucel）治疗患者的 CK 分析显示，应答者和无应答者之间的 CK 参数没有差异；虽然，有一个趋势是高于中值的 C _max与较长的反应持续时间相关。⁵_{然而，较高的 C max}（或 AUC _{0-28 天}）与 3/4 级 CRS 的发生率之间存在关联。⁵在 B-ALL 或慢性淋巴细胞白血病 (CLL) 患者中使用 tisagenlecleucel 进行的类似研究表明，C _max /AUC 与反应之间存在关联。^{6, 7} B-NHL 患者中 axicabtagene ciloleucel 的扩增与反应和神经系统事件相关，但与 CRS 无关。⁸在 MM 环境中，idecabtagene vicleucel C _max与更深的反应和更长的无进展生存期 (PFS) 相关。⁹由于接受 ciltacabtagene autoleucel 的 MM 患者中有 97% 达到了反应，因此无法辨别扩增和反应之间的任何潜在相关性；虽然，CRS 的扩展和严重程度之间似乎存在关联。¹⁰所有这些研究的一个共同点是患者间的高变异性。关于各种 CAR T 细胞产品长期持续存在的动力学以及其他相关隔室（如骨髓、次级淋巴组织和脑脊液）中的动力学的信息较少。

尽管已经证明了施用的细胞剂量与反应之间的关系，但这通常仅限于依赖于某个剂量阈值的反应，并且在该阈值之上并没有始终看到剂量依赖性。^{9, 11-14}此外，尚未观察到给药剂量与后续扩展之间的一致相关性。^{3, 12, 13在之前发表的 Lisocabtagene maraleucel 群体 CK 分析中，在 44–156 × 10 6} CAR T 细胞的测试给药剂量范围内，无法观察到细胞扩增的可辨别的剂量暴露关系。¹⁵事实上，无法辨别与 CAR-T 疗法的剂量-暴露关系在系统药理学模型¹⁶的模拟以及多种 CAR-T 产品的临床 CK 的机制知情模型中得到了很好的协调。¹⁷因此，对 Lisocabtagene maraleucel 等细胞疗法的暴露反应分析结果的解释可能并不完全类似于适用于小分子或生物制剂的结果。而小笠原等人描述的多变量暴露-反应关系。³在其他变异来源的背景下，加深我们对 CAR-T 扩展对临床结果重要性的理解，定量转化为剂量选择决策可能并不简单。通常，作为药物开发临床药理学计划的一部分进行的暴露-反应分析的目的是量化治疗剂的全身暴露与相关临床结果（疗效或毒性）之间的关系。结合对剂量-暴露关系以及全身暴露中相关的内在和外在可变性来源的理解，可以推断出所需的治疗剂量范围，并根据人群和临床使用情况进行适当调整。鉴于由于生物学变异性对 CAR-T 扩增的贡献远大于给药剂量，CAR-T 疗法无法辨别剂量-暴露关系并不少见，临床药理学家将需要重新考虑告知剂量优化的策略。这将需要继续评估系统药理学模型的转化保真度，因为此类模型原则上应有助于解释和扩展从临床观察到的暴露-反应关系的推断，以优化 CAR-T 精准治疗。对 CAR-T 疗法的暴露-反应关系进行药理学分析的其他挑战包括需要仔细考虑永生时间偏差的影响 临床药理学家将需要重新考虑为剂量优化提供信息的策略。这将需要继续评估系统药理学模型的转化保真度，因为此类模型原则上应有助于解释和扩展从临床观察到的暴露-反应关系的推断，以优化 CAR-T 精准治疗。对 CAR-T 疗法的暴露-反应关系进行药理学分析的其他挑战包括需要仔细考虑永生时间偏差的影响 临床药理学家将需要重新考虑为剂量优化提供信息的策略。这将需要继续评估系统药理学模型的转化保真度，因为此类模型原则上应有助于解释和扩展从临床观察到的暴露-反应关系的推断，以优化 CAR-T 精准治疗。对 CAR-T 疗法的暴露-反应关系进行药理学分析的其他挑战包括需要仔细考虑永生时间偏差的影响 这将需要继续评估系统药理学模型的转化保真度，因为此类模型原则上应有助于解释和扩展从临床观察到的暴露-反应关系的推断，以优化 CAR-T 精准治疗。对 CAR-T 疗法的暴露-反应关系进行药理学分析的其他挑战包括需要仔细考虑永生时间偏差的影响 这将需要继续评估系统药理学模型的转化保真度，因为此类模型原则上应有助于解释和扩展从临床观察到的暴露-反应关系的推断，以优化 CAR-T 精准治疗。对 CAR-T 疗法的暴露-反应关系进行药理学分析的其他挑战包括需要仔细考虑永生时间偏差的影响¹⁸在处理疗效终点（如反应持续时间或总生存期）时。尽管在使用细胞扩增的早期“标志性”测量作为暴露指标（例如，输注后 28 天的 AUC）与反应率的关系时，这些问题的关注度较低，但如果所问的问题涉及 CAR 的关系，这些药物统计学考虑因素很重要-T 在事件发生时间分析中对反应持续时间或生存结果的持续性。

最终在体内CAR T 细胞产品的扩增似乎只是影响短期和/或长期疗效的因素之一。其他潜在的贡献者包括起始底物、制造过程中产生的表型、预处理淋巴清除方案、给药的细胞剂量、CAR T 细胞给药后接受的药物以及工程细胞的长期持久性（和表型）。从起始底物的角度来看，由于先前治疗的数量和类型，收集的 T 细胞在个体之间可能存在很大差异，从而导致淋巴细胞减少和/或 T 细胞功能受到抑制。例如，在 idecabtagene vicleucel 用于复发/难治性 MM 患者的 II 期研究中，患者群体的中位数为 6 个先前的治疗线，⁹因此，预计收集到的 T 细胞的质量会非常不同。在更广泛的层面上，转导的 CD4+ 和 CD8+ T 细胞的相对数量可能很重要（并且 Lisocabtagene maraleucel 具有单独的 CD4+ 和 CD8+ T 细胞的制造工艺和输注），但更复杂的免疫表型分析可能会提供更多信息。在一项涉及 CLL 患者的 CAR T 细胞治疗的研究中，发现收集到的具有较高 CD27+CD45RO-CD8+ T 细胞频率的 T 细胞具有类似记忆的特征，并且与持续缓解有关。¹⁹在制造过程中对 T 细胞的操作可能会引发优越的表型，例如记忆样 T 细胞的富集和衰老细胞的相对消耗。这种方法正在使用 bb21217 抗 BCMA 产品进行评估，该产品涉及使用磷酸肌醇 3-激酶抑制剂对细胞进行离体培养。该产品正在进行的 I 期研究的初步结果表明，与低于中值的患者相比，表达 CD27/CD28 的 CD8+ CAR T 细胞数量高于中值的患者的反应持续时间明显更长（P  = 0.0024）。²⁰

由于 CAR T 细胞代表了一种可以随时间复制和维持自身的疗法，因此需要更好地理解驱动体内CAR T 细胞扩增和持久性的机制。对于管理 CAR T 细胞诱导的 CRS 的治疗是否可以消除扩增和疗效，已经进行了很多审查。总的来说，迄今为止的文献表明，在 CAR T 细胞给药后接受皮质类固醇治疗不会对体内扩增或疗效产生负面影响；不过，一项研究发现，在 CAR T 细胞输注后 7 天内使用皮质类固醇治疗与更短的 PFS 相关。^21-24在 Lisocabtagene maraleucel 的群体 CK 模型中，用托珠单抗和/或皮质类固醇治疗被确定为与较高的 C _max和 AUC _{0-28 天}相关的协变量。¹⁵然而，由于这些扩展指标也与需要给予托珠单抗和/或皮质类固醇的 CRS 或神经系统事件相关，因此协变量分析中因果关系的解释并不简单，作者最终得出结论，协变量没有有意义的影响在 Lisocabtagene maraleucel CKs 上。¹⁵目前正在研究其他免疫调节剂（例如，来那度胺）是否可以增强 CAR T 细胞治疗的溶细胞活性和持久性。最后，对 2 名接受 CD19 CAR T 细胞的 CLL 患者的长期随访（7 年）表明，随着时间的推移，T 细胞的表型以及导致长期治疗的克隆的数量和身份发生了变化。长期 CAR T 细胞持久性。²⁵

Ogasawara等人发现，在第一次给药 2 周后第二次给药 Lisocabtagene maraleucel 并没有改变 C _max ³进一步突出了细胞疗法与传统疗法之间的差异，以及需要更广泛地探索控制体内扩增的因素. 确定肿瘤对 CAR T 细胞治疗耐药的机制仍然是一个活跃的研究领域，并且可能与 CAR T 细胞持久性和/或长期细胞毒活性、肿瘤微环境以及肿瘤固有的问题有关。机制，例如抗原表达的丧失或异常的凋亡机制。^26、27

细胞疗法背后的科学正在继续快速发展，导致新方法的发展，例如双靶向 CAR T 细胞（包括共表达不同 CAR 的 T 细胞与不同 CAR T 产品的混合物）、装甲 CAR T 细胞（设计用于分泌细胞因子或抗体样蛋白）、同种异体 CAR T 细胞、CAR-NK 细胞、CAR T 细胞的区域递送，以及将 CAR T 细胞疗法与化疗或免疫治疗药物相结合。随着这些新方法进入人体试验，临床药理学领域将面临全面描述药代动力学、药效学和药理学的新挑战。虽然细胞疗法的药代动力学已经演变成 CK，很明显，理解暴露-反应关系需要的不仅仅是简单地计算在输注后任何给定时间点存在多少工程细胞。T 细胞生物学固有的复杂性以及输注后 CAR T 细胞表型的改变将需要复杂的分子和细胞研究策略来捕捉这些活药物的表型和功能特征。与免疫学家、系统药理学家、数据科学家和其他从事细胞治疗的人的合作至关重要。T 细胞生物学固有的复杂性以及输注后 CAR T 细胞表型的改变将需要复杂的分子和细胞研究策略来捕捉这些活药物的表型和功能特征。与免疫学家、系统药理学家、数据科学家和其他从事细胞治疗的人的合作至关重要。T 细胞生物学固有的复杂性以及输注后 CAR T 细胞表型的改变将需要复杂的分子和细胞研究策略来捕捉这些活药物的表型和功能特征。与免疫学家、系统药理学家、数据科学家和其他从事细胞治疗的人的合作至关重要。

细胞和基因疗法等创新模式正在改变肿瘤学和其他疾病领域的治疗格局，从而产生一系列新的治疗选择。这需要临床药理学家适应和发展新的技能、知识和专业知识。CPT渴望继续发展成为该领域研究和教育出版物的卓越目标期刊。为此，该杂志计划将 2023 年 9 月的主题期刊专门用于“新型治疗方式的临床药理学”，并将在未来几个月发布论文征集。