Gamida Cell — Technical Presentation (2023)
18 slides from Gamida Cell's technical presentation, 2023
Slide 1: Tumor Microenvironment Spatial Analysis after Adoptive NK Cell Therapy for Lymphoma
Tumor Microenvironment Spatial Analysis after Adoptive NK Cell Therapy for Lymphoma Revealed Cross-Talk with Adaptive T-Cell Immunity Veronika Bachanova, Jeffrey S. Miller, Joseph E. Maakaron, Yvette Soignier, Rose Wangen, Ronit Simantov, Dr. Roei Mazor, Ashenafi Tilahun, Martin Felices and Bartosz
Slide 2: Disclosures
Disclosures • Trial Sponsor (NCT03019666). : Gamida Cell • Research Funding: Gamida Cell, Incyte, BMS, Citius, FATE Therapeutics • Advisory Board: Astra Zeneca, ADC, Karyopharma, Takeda
Slide 3: NK cell adoptive therapy can be enhanced with nicotinamide
NK cell adoptive therapy can be enhanced with nicotinamide to improve effector function and tissue retention Natural killer (NK) immune effectors are increasingly being explored for cancer immunotherapy. GDA-201 is a novel nicotinamide ex-vivo expanded metabolically fit allogeneic NK cell product wi
Slide 4: GDA-201 is Novel Allogeneic NK cell Product
GDA-201 is Novel Allogeneic NK cell Product Derived from Healthy Donor and Expanded Ex-Vivo with Nicotinamide and IL-15 Phase 1 trial ClinicalTrials.gov Identifier NCT03019666 Bachanova, ASH 2021 4
Slide 5: Durable responses were observed in patients with B-cell lymphoma
Durable responses were observed in patients with B-cell lymphoma 19 patients with NHL treated (8 had LBCL, 1 MCL, 10 FL) – 13 CR – 1 PR – 5 PD – ORR: 74% • FL: 8 CR, 1PR, 1PD • DLBCL: 5 CR, 3 PD • MCL: 1 PD The median duration of response was 16 months (range 5-36 months) Bachanova, ASH 2020,ASCTC 2
Slide 6: Disease Type and Duration of Response For the R/R NHL
Disease Type and Duration of Response For the R/R NHL R* analysis of PB * Correlative R* R Tissue R biopsy R R * CODEX R* R analysis of PB Correlative NR NR NR NR NR 6
Slide 7: Donor NK cells (GDA-201) detection in blood and lymph nodes
Donor NK cells (GDA-201) detection in blood and lymph nodes Day 7 NK absolute count: 96.54 (39 - 151)] 7
Slide 8: GDA-201 cells proliferate in blood and maintain gene expression profile
GDA-201 cells proliferate in blood and maintain gene expression profile Expression of Ki67 D4 GDA-201 Host NK cells Expression of CD16 Transcriptome profiling suggest maintained gene Host NK cells Donor (GDA-201) expression of GDA201 in vivo which resembles CD56bright NK cells 8
Slide 9: NK cells and T cells subsets in PB are more abundant in responders
NK cells and T cells subsets in PB are more abundant in responders Responders Non-responders Pre-LD Day +7 Pre-LD Day +7 Pt Pt 026 monocytes 028 CD4 CM NK Pre-Chemo Day 7 T TE Pt CD8 CM 027 CD8 EM Pt 024 Pt Pt 9 002 035
Slide 10: Transient host T cells proliferation in blood
Transient host T cells (predominantly CD8 and Treg) proliferation in blood T regs Ki67 high CD8 Ki67 high Absolute count (median) at day 7 in PB % (of lymphs) 900 800 700 600 500 400 300 CD4 Ki67 high NKT Ki67 high 200 100 0 % (of lymphs) T… K PH D4 D8 M EG D4 D3 N CY )E C C TR M C C D8 O LY 4 N CR
Slide 11: Pre and Post-treatment lymph node biopsy (LBCL)
Pre and Post-treatment lymph node biopsy (LBCL) Native stain CD20 Lymphoma CD3 T cells Pre-treatment lymph node biopsy T cells Day 16 post GDA- 201 infusion biopsy 11
Slide 12: Tumor tissues after GDA-201 lack lymphoma B-cells and harbor dense T cell infiltrate
Tumor tissues after GDA-201 lack lymphoma B-cells and harbor dense T cell infiltrate and scattered granzyme+ NK cells Day 16 post-NK cell infusion lymph node biopsy No viable lymphoma left, CD56 NK cells B cell markers: CD19, CD20, NK cells Granzyme B (NK cells; white) PAX5 are all negative CD3 (T c
Slide 13: Tumor tissue after GDA-201 harbors dense CD8 and CD4 cell infiltrate
Tumor tissue after GDA-201 harbors dense CD8 and CD4 cell infiltrate CD8 T cells CD4 T cell Fopx3 Tregs CD3e Ki67 Foxp3 Dense CD8 and CD4 Proliferating T cells inhiltrate in lymph node 13
Slide 14: Pre-treatment biopsy shows follicular lymphoma, low grade
Pre-treatment biopsy shows follicular lymphoma, CD3 H&E low grade B-tumor cells 14 CD20 BCL2
Slide 15: Follicular lymphoma tissue (responder): day +3 post infusion
Follicular lymphoma tissue (responder): day +3 post infusion shows residual lymphoma, increased NK cells and CD8 T cells and persistence of Tregs Dapi Residual CD56 lymphoma Granzyme B Pax5 (B-cells) Regulatory T cells (Tregs) Foxp3+ H&E H&E NK cells 15
Slide 16: Lymph node cell composition analysis from responders
Lymph node cell composition analysis from responders Pt 026 Pt 009 CD8 (%) CD4 (%) (day +16) (day +3) CyTOF T cells Dg LBCL FL CXCR3 75 52 T cells 78% (lymph) 62% (lymph) CXCR5 3 27 NK cells 10% 13% CD8 35% 97% CCR4 36 61 -Eff Mem 73% 1% -Term Eff 25% 98% CCR6 7 10 -Cen M 1% 1% CCR7 3.5 2.6 CD4 63%
Slide 17: Conclusions
Conclusions • Spatial analysis of “on treatment” tumor biopsies suggests NK cells trafficking to tumor microenvironment (10-15 % of all cells) • T cells were the predominant population infiltrating tumor sites with variable proportion between 60-80% of cellularity • • Both CD8 and CD4 subsets have b
Slide 18: Acknowledgments
Acknowledgments • Patients and their families BMT/CT Program at University MCT Facility • University of Minnesota BMT and of Minnesota David McKenna Cellular Therapy Program Jeffrey Miller-director Mark Juckett Clinical Trial Office Joseph Maakaron Ashley Lyle Daniel Weisdorf Shernan Holtan Patholog