The Role of Fc Receptors on the Effectiveness of Therapeutic Monoclonal Antibodies

Since the approval of the first monoclonal antibody (mAb) in 1986, a huge effort has been made to guarantee safety and efficacy of therapeutic mAbs. As of July 2021, 118 mAbs are approved for the European market for a broad range of clinical indications. In order to ensure clinical efficacy and safety aspects, (pre-)clinical experimental approaches evaluate the respective modes of action (MoA). In addition to antigen-specificity including binding affinity and -avidity, MoA comprise Fc-mediated effector functions such as antibody dependent cellular cytotoxicity (ADCC) and the closely related antibody dependent cellular phagocytosis (ADCP). For this reason, a variety of cell-based assays have been established investigating effector functions of therapeutic mAbs with different effector/target-cell combinations and several readouts including Fcγ receptor (FcγR)-mediated lysis, fluorescence, or luminescence. Optimized FcγR-mediated effector functions regarding clinical safety and efficacy are addressed with modification strategies such as point mutations, altered glycosylation patterns, combination of different Fc subclasses (cross isotypes), and Fc-truncation of the mAb. These strategies opened the field for a next generation of therapeutic mAbs. In conclusion, it is of major importance to consider FcγR-mediated effector functions for the efficacy of therapeutic mAbs.     

转基因植物重组糖蛋白糖基化研究现状与植物重组糖蛋白糖结构的改造策略

本文综述了转基因植物重组蛋白质糖基化的研究现状,并着重介绍了转基因重组蛋白N-糖链的结构以及改造植物重组糖蛋白的糖结构的两种重要策略——将蛋白表达产物滞留在细胞内质网中或改变植物的糖基化过程。最后对转基因植物重组蛋白糖链研究未来的发展作了展望。     

Correction to Psychotherapist Mindfulness and the Psychotherapy Process, Bruce et al (2010).

Reports an error in Psychotherapist mindfulness and the psychotherapy process by Noah G. Bruce, Rachel Manber, Shauna L. Shapiro and Michael J. Constantino (Psychotherapy: Theory, Research, Practice, Training, 2010[Mar], Vol 47[1], 83-97). The order of authorship and the affiliations of the authors was incorrectly printed. The correct order and affiliations are as follows: Noah Bruce, Shauna L. Shapiro, Michael J. Constantino, and Rachel Manber; Kaiser Permanente, Santa Clara University, University of Massachusetts, Stanford University. (The following abstract of the original article appeared in record 2010-05168-010.) A psychotherapist’s ability to relate to his or her patients is essential for decreasing patient suffering and promoting patient growth. However, the psychotherapy field has identified few effective means for training psychotherapists in this ability. In this conceptual article, we propose that mindfulness practice may be a means for training psychotherapists to better relate to their patients. We posit that mindfulness is a means of self-attunement that increases one’s ability to attune to others (in this case, patients) and that this interpersonal attunement ultimately helps patients achieve greater self-attunement that, in turn, fosters decreased symptom severity, greater well-being, and better interpersonal relationships. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

窄治疗指数药物的生物等效性评价进展

近年来窄治疗指数类药物的生物等效性评价备受关注,关于窄治疗指数药物生物等效性如何评价,一些要点问题尚存很大的争议。目前国内尚无相关指导原则,本文分析和介绍了窄治疗指数类药物生物等效性研究的困难及主要解决方法,参考国内外法规、指导原则及相关文献,对窄治疗窗药物生物等效性评价及参比制剂校正的平均生物等效性（RSABE）方法展开介绍,以期对我国窄治疗指数类药物的仿制药质量与疗效一致性评价工作提供借鉴和帮助。     

Pharmacokinetics of Doxazosin Gastrointestinal Therapeutic System after Multiple Administration in Korean Healthy Volunteers

Doxazosin mesylate is a selective alpha-adrenoreceptor antagonist for the treatment of hypertension and benign prostatic hyperplasia. A simple high performance liquid chromatographic method has been developed and validated for the quantitative determination of doxazosin in plasma. A reversed phase C18 column was used for the separation of doxazosin and prazosin (internal standard) with a mobile phase composed of water ? acetonitrile ? triethylamine (68:32:0.2 v/v, pH 5.0) at a flow rate of 1.2 mL/min. The fluorescence detector was operated at 246 (excitation) and 389 nm (emission). Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification of 1 ng/mL. Recovery of doxazosin from human plasma was greater than 93.4%. Doxazosin was stable in human plasma under various storage conditions. This method was used successfully for a pharmacokinetic study in plasma after oral administration of multiple 4-mg dose of doxazosin gastrointestinal therapeutic system formulation to 16 healthy volunteers. At steady state the mean area under the curve for a dosing interval and elimination half-life were calculated to be 367.0 ± 63.5 ng · hr/mL and 29.2 ± 4.5 hr, respectively. There was no difference in pharmacokinetic parameters between male and female.     

Factor structure and validity of the Therapeutic Factors Inventory–Short Form.

Clinical group practice is commonly guided by the assumption that 11 distinct therapeutic factors operate in psychotherapy groups. This assumption should be closely examined due to the emerging evidence of fewer, more global therapeutic factors. The present study was conducted to continue the development of the Therapeutic Factors Inventory–Short Form (TFI–S) and focused on confirming its factor structure and evaluating aspects of its concurrent, discriminant, and predictive validity. A sample comprising a total of 435 clients from 52 distinct therapy groups at eight different clinical sites in the U.S. and Canada was obtained. Structural equation modeling analyses indicated that a four-factor model had a reasonably good fit to the TFI–S rating data, and it provided indications for further refinement of the constituent items. The analyses resulted in a revised, 19-item measure, the Therapeutic Factors Inventory–19 (TFI–19). Three-level HLM analyses demonstrated that the four factors were sensitive to change in member perceptions over time. Significant and meaningful relationships between the TFI–19 factors and subscales of the Group Climate Questionnaire-Short Form provided support for the concurrent validity of the TFI–19. Two-level HLM analyses identified significant relationships between the TFI–19 factors and posttreatment status on symptomatic and interpersonal distress, thereby supporting the predictive validity of the TFI–19. The findings suggest that the TFI–19 may be a useful instrument to assess group members' perceptions of more global therapeutic factors. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Questioning the couch: Historical and clinical perspectives.

Since the beginning of the last century, when Freud introduced the couch in the psychoanalytic room, a number of “objects” have been removed or renovated, yet the couch has almost always remained in place, at least officially. This article has two distinct aims. The first is to offer a reconstruction of the psychoanalytic history of this element of the setting. The second is to rethink the couch, saving it from being reduced to a mere icon. Recent contributions coming from affective neurosciences, infant research, and psychotherapy research seem to question the utility of this element and the nature of the very mechanisms of its therapeutic action. The authors wonder whether the use of the couch is primarily protective for the therapist rather than necessarily helpful for all patients. Taking into account these observations implies bringing the couch out from a silent dimension and reflecting on its role in the conception of therapeutic action and mental functioning. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Two aspects of the therapeutic alliance: Differential relations with depressive symptom change.

Objective: The therapeutic alliance has been linked to symptom change in numerous investigations. Although the alliance is commonly conceptualized as a multidimensional construct, few studies have examined its components separately. The current study explored which components of the alliance are most highly associated with depressive symptom change in cognitive therapy (CT). Method: Data were drawn from 2 published randomized, controlled clinical trials of CT for major depressive disorder (n = 105, mean age = 40 years, female = 62%, White = 82%). We examined the relations of 2 factor-analytically derived components of the Working Alliance Inventory (WAI; Horvath & Greenberg, 1986, 1989) with symptom change on the Beck Depression Inventory—II (BDI–II; Beck, Steer, & Brown, 1996) that occurred either prior to or subsequent to the examined sessions. WAI ratings were obtained at an early and a late session for each therapist–patient dyad. Results: Variation in symptom change subsequent to the early session was significantly related to the WAI factor that assesses therapist–patient agreement on the goals and tasks of therapy but not to a factor assessing the affective bond between therapist and patient. In contrast, both factors, when assessed in a late session, were significantly predicted by prior symptom change. Conclusions: These findings may reflect the importance, in CT, of therapist–patient agreement on the goals and tasks of therapy. In contrast, the bond between therapist and patient may be more of a consequence than a cause of symptom change in CT. The implications of these results and directions for future research are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Alliance in individual psychotherapy.

This article reports on a research synthesis of the relation between alliance and the outcomes of individual psychotherapy. Included were over 200 research reports based on 190 independent data sources, covering more than 14,000 treatments. Research involving 5 or more adult participants receiving genuine (as opposed to analogue) treatments, where the author(s) referred to one of the independent variables as “alliance,” “therapeutic alliance,” “helping alliance,” or “working alliance” were the inclusion criteria. All analyses were done using the assumptions of a random model. The overall aggregate relation between the alliance and treatment outcome (adjusted for sample size and non independence of outcome measures) was r = .275 (k = 190); the 95% confidence interval for this value was .25–.30. The statistical probability associated with the aggregated relation between alliance and outcome is p     

Repairing alliance ruptures.

In this article, we review the existing empirical research on the topic of therapeutic alliance ruptures in psychotherapy. Ruptures in the therapeutic alliance are defined as episodes of tension or breakdown in the collaborative relationship between patient and therapist. Two meta-analyses were conducted. The first reviewed studies examining the relation between rupture-repair episodes and treatment outcome (r = .24, z = 3.06, 95% CI [.09, .39], p = .002, k = 3, N = 148). The second meta-analysis reviewed the research examining the impact on treatment outcome of training therapists in the use of alliance rupture intervention principles (prepost r = .65, z = 5.56, 95% CI [.46, .78], p k = 8, N = 376). Both meta-analyses provided promising evidence regarding the relevance of alliance rupture-repair processes to therapeutic outcome. The limitations of the research reviewed are discussed as well as practice implications for repairing the inevitable alliance ruptures in psychotherapy. (PsycINFO Database Record (c) 2011 APA, all rights reserved)