Autologous EBV-specific T cell treatment results in sustained responses in patients with advanced extranodal NK/T lymphoma: results of a multicenter study.

We conducted a phase II clinical trial to develop an autologous EBV-specific T cell product (baltaleucel T) for advanced, relapsed ENKTL. Among 47 patients who provided whole blood starting material for manufacturing the product, 15 patients received a median of 4 doses of baltaleucel T. Thirty-two (68%) patients did not receive baltaleucel-T due to manufacturing failure, rapid disease progression, and death. Of the 15 patients, 10 patients had measurable disease at baseline (salvage cohort), and 5 patients had no disease at baseline assessment (adjuvant cohort). In the 15 patients, the median follow-up duration was 10.2 months (range 2.0-23.5 months), median progression-free survival (PFS) was 3.9 months, and the median overall survival (OS) was not reached. Patients in the salvage cohort achieved a 30% complete response (CR) and a 50% overall response rate (ORR). In the adjuvant cohort, disease progression was reported in three patients and two patients did not relapse during study follow-up. When we compared survival outcomes of seven responders and eight non-responders, the PFS (P = 0.001) and OS (P = 0.014) of responders proved statistically superior to that of non-responders. Baltaleucel-T was well tolerated. We have performed a phase II clinical trial of autologous EBV-specific T cell treatment (baltaleucel-T) in R/R ENKTL. Autologous EBV-specific T cells were well tolerated and demonstrated single-agent activity in R/R ENTKL.

Current state of U.S. Food and Drug Administration regulation for cellular and gene therapy products: potential cures on the horizon.

Cellular & Gene Therapies (CGTs) are complex products, which have been key foci of the International Society for Cell & Gene Therapy (ISCT). For this ISCT North American Legal & Regulatory Affairs Committee review publication, CGTs include but are not limited to somatic cell-based therapies, pluripotent cell-derived cell-based therapies, gene- or non-gene-modified or gene edited versions of these cell-based therapies, in vivo gene therapies, organ/tissue engineered products, and relevant combination products. These products are regulated by the Food and Drug Administration (FDA) in the United States. This publication reviews selected laws, regulations, guidance, definitions, processes, types of meetings and submissions, and other key factors that the FDA follows and implements to regulate and support development of these types of products. These factors may be considered in order to help current and potential product developers/sponsors/applicants navigate through FDA regulatory pathways. We also review expedited programs including types of Designations available at the FDA, and their specific eligibility criteria. We include FDA and other stakeholder resources to consider regarding CGT regulation, to help prepare for CGT development and subsequent FDA approval.

A changing time: the International Society for Cellular Therapy embraces its industry members.

The last decade has seen a dramatic rise in the development of new cellular therapeutics in a wide range of indications. There have been acceptable safety profiles reported in early studies using blood-derived and adherent stem cell products, but also an inconsistent efficacy record. Further expansion has been hindered in part by a lack of capital (both private and public) and delayed entry into the cell therapy space by large healthcare and pharmaceutical companies, those members of the industry most reliably able to initiate and maintain advanced-phase clinical trials. With recognition that the International Society for Cellular Therapy (ISCT) is uniquely positioned to serve the global translational regenerative medicine research community as a network hub for scientific standards and policy, the ISCT commissioned the establishment of an Industry Task Force (ITF) to address current and future roles for industry. The objectives of the ITF were to gather information and prioritize efforts for a new Commercialization Committee (CC) and to construct innovative platforms that would foster constructive and synergistic collaborations between industry and ISCT. Recommendations and conclusions of the ITF included that the new CC: (1) foster new relationships with therapeutic and stem cell societies, (2) foster educational workshops and forums to cross-educate and standardize practices, (3) create industry subcommittees to address priority initiatives, with clear benchmarks and global implementation, and (4) establish a framework for a greater industry community within ISCT, opening doors for industry to share the new vision for commercialization of cell therapy, emphasizing the regenerative medicine space.