T-cell tracking, safety, and effect of low-dose donor memory T-cell infusions after αβ T cell-depleted hematopoietic stem cell transplantation

Detecting T-cell clonal expansions and quantifying clone survival using deep profiling of immune repertoires

“…The analysis of the different types of transplants used for HSCT revealed substantial differences in the DLI and non-DLI samples ( Figure 5A ). While the capture probability of the T-cell clonotypes from transplants containing the unperturbed TCR repertoire (non-DLI samples) resulted in overall agreement with the log-linear model as shown previously, the transplants depleted for CD45RA + cells (DLI samples), i.e., mostly consisting of memory T cells, showed little dependence on the donor and transplant repertoire diversity, but overall had a higher survival rate, as expected from previous observations ( 7 ). Notably, while conventional analysis of the correspondence between the clonotype frequencies in the donor and transplant showed some significant correlations ( Figure 5B ), the overall correlation coefficient values (effect sizes) were low, and there were no differences between the DLI and non-DLI samples.…”

“…To evaluate the clonal survival of T cells from distinct subsets, we also used previously unpublished data in the HSCT dataset from the study by Blagov et al. ( 7 ). These data represent the TCRβ repertoires of the CD4 + and CD8 + cell fractions obtained by fluorescence-activated cell sorting (FACS), as well as the central memory T (Tcm) and effector memory T (Tem) cells.…”

“…A large number of recent works have employed immune repertoire profiling methods based on high-throughput sequencing techniques to study the dynamics of the T-cell repertoire by tracking the clonal emergence, survival, and expansion in response to various immune stimuli, such as vaccination ( 6 ) and hematopoietic stem cell transplantation (HSCT) ( 7 ), by monitoring minimal residual disease ( 8 ), detecting the autoimmune response ( 9 ), and assessing the aging of the adaptive immune system ( 2 , 10 ). One of the most important applications of high-throughput TCR profiling in the coronavirus disease 2019 (COVID-19) pandemic era is the tracking of the response to pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in the course of infection, during follow-up, after infection, and during assay of the vaccination efficiency ( 11 ).…”

Phase I dose-escalation single centre clinical trial to evaluate the safety of infusion of memory T cells as adoptive therapy in COVID-19 (RELEASE)

“…Nevertheless, previous reports with allogeneic haematopoietic stem cell transplantation (HSCT) shows that grafts containing CD45RA À T cells rise 2-year overall survival up to 78% (95% CI 59À89%), in allogeneic adult myeloablative HSCT with a grade IIÀIV aGVHD (66%; 95% CI 41À74%) [24]. Probably the most similar scenario to our adoptive cell therapy for COVID-19 patients is the use of CD45RA À donor lymphocyte infusion (DLI) in haploidentical setting to boost immune recovery controlling virus reactivation and avoiding GvHD [22,25]. Given the appropriate conditions it should be a safe approach even with inflammatory disease and mismatch setting.…”

Donor selection for adoptive cell therapy with CD45RA− memory T cells for patients with coronavirus disease 2019, and dexamethasone and interleukin-15 effects on the phenotype, proliferation and interferon gamma release

“…4 , 15 We and other authors have shown the antiviral properties of CD45RA − memory T cells in hematopoietic stem cell transplantation and COVID-19 settings. 25 , [38] , [39] , [40] , [41] We have demonstrated the safety and feasibility of adoptive cell therapy using CD45RA − memory T cells containing SARS-CoV-2 specific T cells in hospitalized COVID-19 patients. In this approach, we pursued to increase the pool of lymphocytes in patients with lymphopenia, exerting an antiviral effect on the coronavirus and protecting the patient from other viruses that the donor encountered.…”