loading
loading
NIH grant 1R01CA318641-01: CD45RA-DEPLETED CD19-CAR T CELL CONSOLIDATION AFTER TCR alphabeta+ T CELL-DEPLETED HAPLOIDENTICAL HEMATOPOIETIC CELL TRANSPLANTATION FOR RELAPSED/REFRACTORY CD19+ ALL AND LYMPHOMA
Institute: {'code': 'CA', 'abbreviation': 'NCI', 'name': 'National Cancer Institute', 'admin_org_id': '12500008', 'admin_funding_url': ''}. PI: Swati Naik. Award: $737023.
Start: 2026-07-23T00:00:00.
ABSTRACT
Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative cellular therapy strategy for pediatric
patients with high-risk B-cell ALL but is associated with significant complications, the most consequential of which
are relapse, GVHD and the devasting consequences of use of total body irradiation (TBI) as conditioning therapy.
CAR T cell therapy has emerged as a novel, powerful cellular therapy for the treatment of relapsed/refractory B-
ALL. We now propose to combine these two powerful cellular therapies, namely allo-HCT and transplant donor-
derived allogeneic CAR T cell therapy to minimize the risk of relapse and eliminate TBI. In addition, we will use
graft engineering approaches to minimize GVHD by select use of immune effectors. We will use for : i) The
transplant platform : TCRαβ T cell depletion approach as TCRαβ T cells are key mediators of GVHD and ii) the
CART platform : a naïve T-cell depleted product as naïve T cells are key mediators of GVHD leaving behind
memory T cells which do not cause GVHD, to manufacture our CAR T cell product, (CD19-CAR(Mem) T cells).
We hypothesize that combining allogeneic transplant donor-derived CD19-CAR(Mem) T cells infusion
prophylactically after TCRαβ+ T cell depleted alloHCT will provide complimentary and augmented
immune-mediated graft-versus-leukemia effects which will decrease risk of relapse and allow for the use
of a TBI- free conditioning regimen while maintaining low rates of GVHD. A secondary hypothesis is that
that carefully orchestrated correlative studies are needed to decipher the mechanisms of response and
resistance of our approach to enable future innovation. We will test these hypotheses in two aims: Aim 1: To
assess feasibility, safety, and clinical outcomes of prophylactic CD19-CAR(Mem) T cell infusion after TCRαβ+
depleted transplant and reduced-toxicity TBI-free conditioning. Aim 2: To characterize the fate and function of
infused CAR T cells, their impact on immune reconstitution, and mechanisms of response and resistance using
advanced state-of-the art correlative testing including TCR analysis and 10x scRNAseq analysis of immune cells
and malignant blasts. If successful, this strategy could enable powerful, TBI-free transplant strategies that will
lead to long-term remissions with minimal morbidity and mortality for pediatric B-ALL. Extensive correlative data
generated will provide critical information for the field of transplantation and cell therapy. While this application
is focused on pediatric B-ALL, these findings could be readily applied to broader pediatric and adult populations
enabling novel, innovative, combinatorial cell-therapy based approaches across the spectrum of high-risk
hematological malignancies.document fetched 2026-08-02 08:24