Cellular therapy with GDA-201 and rituximab was well tolerated and yielded an overall response rate of 74% in 19 patients with advanced NHL. GDA-201 cells were detected for up to 14 days in blood, bone marrow, and tumor tissues and maintained a favorable metabolic profile. The safety and efficacy of GDA-201 in this study support further development as a cancer therapy.
All patients received lymphodepleting chemotherapy followed by 2 infusions of GDA-201 at days 0 and 2 combined with rituximab and low dose IL2. Overall, our findings from multiplexed spatial profiling support a model in which adoptive NK cell infusions trigger profound immune microenvironment changes which support the influx of host T cells. This occurs early post GDA-201 infusion concurrent with limited blood compartment persistence. Our findings suggest cross-talk with the adaptive arm of the immune system and effective tumor elimination.
Cells maintained expression of CD56 and CD16 and expressed high levels of the homing and retention marker CD62L. Cryopreserved GDA-201 showed high cytotoxicity and enhanced potency as detected by intracellular secretion of IFN-
Methods HER2-CAR-NK cells were developed based on a single-chain variable fragment (scFv) of the widely used humanized monoclonal antibody trastuzumab. Informed consent has been approved by the ECs. The Israeli template of informed consent is in used and it includes study specific information (e.g. study goal, design, method, duration, risks, etc.).
Moreover, NAM increases cellular metabolic fitness, energy charge, and efficiency of glucose consumption, potentially imparting a protective effect against oxidative stress in the tumor microenvironment. These data offer insight into the mechanism of improved persistence, proliferation, and cytotoxicity observed in in vivo and clinical studies of GDA-201.
almost 3 years ago
IO biomarker
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MDM2 (E3 ubiquitin protein ligase) • LAG3 (Lymphocyte Activating 3) • CDK4 (Cyclin-dependent kinase 4) • IL2RA (Interleukin 2 receptor, alpha) • CD44 (CD44 Molecule) • FOXP1 (Forkhead Box P1) • CALR (Calreticulin) • RPS6 (Ribosomal Protein S6) • STAT1 (Signal Transducer And Activator Of Transcription 1) • CD40LG (CD40 ligand) • CXCR3 (C-X-C Motif Chemokine Receptor 3) • GATA3 (GATA binding protein 3) • HSPH1 (Heat Shock Protein Family H (Hsp110) Member 1) • CD86 (CD86 Molecule) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1) • PABPC1 (Poly(A) Binding Protein Cytoplasmic 1)
Pts with R/R B-cell NHL received lymphodepleting (LD) chemotherapy with cyclophosphamide (400mg/m 2 IV x 3d) and fludarabine (30 mg/m 2 /d IV x 3d), followed by GDA-201 (days 0 and 2) and low-dose IL-2 (6 million units sc x 3 doses at days 0,2,4). Cellular therapy using GDA-201 with rituximab is well-tolerated, and demonstrated significant clinical activity in heavily pre-treated pts with advanced NHL. A cytokine surge following LD chemotherapy appears to be associated with clinical activity. Phase II studies in aggressive and indolent NHL cohorts are planned.
3 years ago
Clinical • IO biomarker
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SELL (Selectin L)
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Rituxan (rituximab) • cyclophosphamide • fludarabine IV • GDA-201