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Allogeneic CAR Cell Therapy-More Than a Pipe Dream.

ABSTRACT: Adoptive cellular immunotherapy using immune cells expressing chimeric antigen receptors (CARs) has shown promise, particularly for the treatment of hematological malignancies. To date, the majority of clinically evaluated CAR cell products have been derived from autologous immune cells. While this strategy can be effective it also imposes several constraints regarding logistics. This includes i) availability of center to perform leukapheresis, ii) necessity for shipment to and from processing centers, and iii) time requirements for product manufacture and clinical release testing. In addition, previous cytotoxic therapies can negatively impact the effector function of autologous immune cells, which may then affect efficacy and/or durability of resultant CAR products. The use of allogeneic CAR cell products generated using cells from healthy donors has the potential to overcome many of these limitations, including through generation of "off the shelf" products. However, allogeneic CAR cell products come with their own challenges, including potential to induce graft-versus-host-disease, as well as risk of immune-mediated rejection by the host. Here we will review promises and challenges of allogeneic CAR immunotherapies, including those being investigated in preclinical models and/or early phase clinical studies.

SUBMITTER: Caldwell KJ

PROVIDER: S-EPMC7821739 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Allogeneic CAR Cell Therapy-More Than a Pipe Dream.

Caldwell Kenneth J KJ Gottschalk Stephen S Talleur Aimee C AC

Frontiers in immunology 20210108

Adoptive cellular immunotherapy using immune cells expressing chimeric antigen receptors (CARs) has shown promise, particularly for the treatment of hematological malignancies. To date, the majority of clinically evaluated CAR cell products have been derived from autologous immune cells. While this strategy can be effective it also imposes several constraints regarding logistics. This includes i) availability of center to perform leukapheresis, ii) necessity for shipment to and from processing c ...[more]

PMID: 33488631

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Project description:There are limited data on patient experience after chimeric antigen receptor (CAR) T-cell therapy, especially in comparison to autologous and allogeneic transplantation, which are more established forms of cellular therapy. We prospectively evaluated longitudinal patient-reported quality of life (QoL), symptom burden and cognition after CAR-T cell therapy and compared it with prospective cohorts of patients undergoing autologous stem cell transplantation (autoSCT) and allogeneic SCT (alloSCT). This was a single center study. The primary endpoint was change in QoL. Secondary endpoints were patient-reported adverse events (PRO-AEs) measured by Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and cognitive function (NeuroQOLv2 questionnaire). Time profile of PRO-AEs was evaluated using longitudinal analysis, Toxicity over Time (ToxT). Patients completed questionnaires at baseline, week 2 and monthly for 6 months. One hundred four patients were evaluable (CAR-T: 34, autoSCT: 33, alloSCT: 37). Baseline QoL was similar across groups. We observed a short-term decline in QoL in all groups that gradually returned to baseline. The nadir in QoL was at week 2 and coincided with peak in symptom burden. The decline in overall QoL, physical and functional well-being was significantly less with CAR-T versus SCT groups and returned to baseline faster. Patients in the alloSCT group experienced the greatest symptom burden, greater decrease in performance status, largest short-term decline in QoL and slowest recovery. This study provides comprehensive data comparing QoL, PRO-AEs and cognition following CAR-T cell therapy versus autoSCT and alloSCT, and the first application of ToxT to PRO-CTCAE data. Short-term QOL, including physical and functional domains was better in the CAR-T group versus SCT groups, although all groups experienced an initial decline coinciding with peak symptoms. These data can serve as a guide for patient education, symptom management, and future studies in CAR-T cell therapy.

Dataset Information

Allogeneic CAR Cell Therapy-More Than a Pipe Dream.

Publications

Allogeneic CAR Cell Therapy-More Than a Pipe Dream.

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