Selective depletion of naïve T cells by targeting CD45RA

Naik, Swati

doi:10.3389/fonc.2022.1009143

Cited by 5 publications

(3 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The predominant memory T-cell content in the infused graft likely made large doses of infused haploidentical T cells tolerable as > 10 5 unmanipulated haploidentical T cells/kg cause GVHD. As reported by others [ 49 ], aGVHD in our study was responsive to therapy and required systemic steroids for a median of < 2 months, confirming preclinical studies that have highlighted differences between aGVHD induced by naïve and memory T cells [ 60 , 61 ]. In addition, we used a short course of sirolimus or mycophenolate mofetil as GVHD prophylaxis.…”

Section: Discussionsupporting

confidence: 90%

Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial

Naik,

Li,

Talleur

et al. 2024

J Hematol Oncol

Self Cite

View full text Add to dashboard Cite

Background Relapse remains a challenge after transplantation in pediatric patients with hematological malignancies. Myeloablative regimens used for disease control are associated with acute and long-term adverse effects. We used a CD45RA-depleted haploidentical graft for adoptive transfer of memory T cells combined with NK-cell addback and hypothesized that maximizing the graft-versus-leukemia (GVL) effect might allow for reduction in intensity of conditioning regimen. Methods In this phase II clinical trial (NCT01807611), 72 patients with hematological malignancies (complete remission (CR)1: 25, ≥ CR2: 28, refractory disease: 19) received haploidentical CD34 + enriched and CD45RA-depleted hematopoietic progenitor cell grafts followed by NK-cell infusion. Conditioning included fludarabine, thiotepa, melphalan, cyclophosphamide, total lymphoid irradiation, and graft-versus-host disease (GVHD) prophylaxis consisted of a short-course sirolimus or mycophenolate mofetil without serotherapy. Results The 3-year overall survival (OS) and event-free-survival (EFS) for patients in CR1 were 92% (95% CI:72–98) and 88% (95% CI: 67–96); ≥ CR2 were 81% (95% CI: 61–92) and 68% (95% CI: 47–82) and refractory disease were 32% (95% CI: 11–54) and 20% (95% CI: 6–40). The 3-year EFS for all patients in morphological CR was 77% (95% CI: 64–87) with no difference amongst recipients with or without minimal residual disease (P = 0.2992). Immune reconstitution was rapid, with mean CD3 and CD4 T-cell counts of 410/μL and 140/μL at day + 30. Cumulative incidence of acute GVHD and chronic GVHD was 36% and 26% but most patients with acute GVHD recovered rapidly with therapy. Lower rates of grade III-IV acute GVHD were observed with NK-cell alloreactive donors (P = 0.004), and higher rates of moderate/severe chronic GVHD occurred with maternal donors (P = 0.035). Conclusion The combination of a CD45RA-depleted graft and NK-cell addback led to robust immune reconstitution maximizing the GVL effect and allowed for use of a submyeloablative, TBI-free conditioning regimen that was associated with excellent EFS resulting in promising long-term outcomes in this high-risk population. The trial is registered at ClinicalTrials.gov (NCT01807611).

show abstract

Section: Discussionsupporting

confidence: 90%

Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial

Naik,

Li,

Talleur

et al. 2024

J Hematol Oncol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent advancements in developing good manufacturing practices (GMP) for CD45RA + cell depletion have been described, facilitating its potential application in CAR T cell manufacturing ( Zheng et al, 2018 ). This has been further tested in the treatment of subjects with lymphocytic leukemia, where the graft-versus-leukemia (GVL) effect is optimized while reducing the risk of graft-versus-host disease (GVHD) ( Dutt et al, 2007 ; Biernacki et al, 2020 ; Kim-Hoehamer et al, 2023 ; Naik and Triplett, 2023 ).…”

Section: Manufacturing Approaches For Car T-cellsmentioning

confidence: 99%

Current advances in experimental and computational approaches to enhance CAR T cell manufacturing protocols and improve clinical efficacy

Colina,

Shah,

Shah

et al. 2024

Front. Mol. Med

View full text Add to dashboard Cite

Since the FDA’s approval of chimeric antigen receptor (CAR) T cells in 2017, significant improvements have been made in the design of chimeric antigen receptor constructs and in the manufacturing of CAR T cell therapies resulting in increased in vivo CAR T cell persistence and improved clinical outcome in certain hematological malignancies. Despite the remarkable clinical response seen in some patients, challenges remain in achieving durable long-term tumor-free survival, reducing therapy associated malignancies and toxicities, and expanding on the types of cancers that can be treated with this therapeutic modality. Careful analysis of the biological factors demarcating efficacious from suboptimal CAR T cell responses will be of paramount importance to address these shortcomings. With the ever-expanding toolbox of experimental approaches, single-cell technologies, and computational resources, there is renowned interest in discovering new ways to streamline the development and validation of new CAR T cell products. Better and more accurate prognostic and predictive models can be developed to help guide and inform clinical decision making by incorporating these approaches into translational and clinical workflows. In this review, we provide a brief overview of recent advancements in CAR T cell manufacturing and describe the strategies used to selectively expand specific phenotypic subsets. Additionally, we review experimental approaches to assess CAR T cell functionality and summarize current in silico methods which have the potential to improve CAR T cell manufacturing and predict clinical outcomes.

show abstract

“…Outcomes after allogeneic HCT have improved over time, owing to advances in both transplantation and supportive care approaches, which, in turn, contribute to improved leukemia-free survival (LFS) as well as a reduction in transplant-related mortality (TRM) [59][60][61][62]. This includes progress related to conditioning regimens, donor typing, graft manipulation, expansion of access to alternative donors, graft-versus-host disease (GVHD) prophylaxis and treatment, and infection prevention and control [62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]. Furthermore, advances in leukemic diagnostics, genetic subtyping, and leukemia-directed therapies have decreased the number of patients proceeding to HCT and, for those who are deemed candidates, have enhanced the depth of remission which patients achieve prior to HCT [9, 48,49].…”

Section: Cellular Therapiesmentioning

confidence: 99%

What Is Next in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia

2023

View full text Add to dashboard Cite

Cure rates now exceed 90% in many contemporary trials for children with B-cell acute lymphoblastic leukemia (B-ALL). However, treatment remains suboptimal, and therapy is toxic for all patients. New treatment options potentially offer the chance to reduce both treatment resistance and toxicity. Here, we review recent advances in ALL diagnostics, chemotherapy, and immunotherapy. In addition to describing recently published results, we also attempt to project the impact of these new developments into the future to imagine what B-ALL therapy may look like in the next few years.

show abstract

Selective depletion of naïve T cells by targeting CD45RA

Cited by 5 publications

References 82 publications

Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial

Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial

Current advances in experimental and computational approaches to enhance CAR T cell manufacturing protocols and improve clinical efficacy

What Is Next in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia

Contact Info

Product

Resources

About