Treg InFlux present

Preparation of Highly Purified Regulatory FoxP3+ T Cells Preparation of Highly Purified Regulatory FoxP3+ T Cells

for Clinical Applicationsfor Clinical Applications

Randall ArmstrongRandall ArmstrongStanford Blood & Marrow Transplant ProgramStanford Blood & Marrow Transplant Program

Cell Therapy FacilityCell Therapy FacilityStanford HealthcareStanford Healthcare

Classically CD4+CD25high (IL2R Classically CD4+CD25high (IL2R -chain)-chain)•

CD127low (IL7R)CD127low (IL7R)

~3-10% of CD4+ T-cells~3-10% of CD4+ T-cells

Treg inhibit HLA-mismatched stimulated T-cell proliferationTreg inhibit HLA-mismatched stimulated T-cell proliferation

FoxP3+ Regulatory T cellsFoxP3+ Regulatory T cells

Application of regulatory T cells in allogeneic BM Application of regulatory T cells in allogeneic BM transplantationtransplantation

Interest in adoptive Treg immunotherapy for autoimmune diseases and Interest in adoptive Treg immunotherapy for autoimmune diseases and GVHDGVHD

T cell depletion decreases incidence and severity of GVHD but increases T cell depletion decreases incidence and severity of GVHD but increases the risk of graft rejection, relapse, and post-transplant infectionthe risk of graft rejection, relapse, and post-transplant infection

Haploidentical donor T cells increase risk of severe GVHDHaploidentical donor T cells increase risk of severe GVHD

Nonablative conditioning regimens for BMT may be unsuitable for Nonablative conditioning regimens for BMT may be unsuitable for patients with high risk diseasepatients with high risk disease

Steroid-refractory acute and chronic GVHD Steroid-refractory acute and chronic GVHD

Graft vs. Host DiseaseGraft vs. Host Disease

Major cause of transplant-related morbidity and mortalityMajor cause of transplant-related morbidity and mortality Chronic GVHD occurs in ~ 30%-40% of BMT recipientsChronic GVHD occurs in ~ 30%-40% of BMT recipients Acute GVHD ~5%-10% occurrenceAcute GVHD ~5%-10% occurrence T-cell proliferation initiated by HLA-mismatched APC interactionT-cell proliferation initiated by HLA-mismatched APC interaction Target organs:Target organs:

• SkinSkin• GutGut• LiverLiver• Mucous membranesMucous membranes

Treatments include:Treatments include:• PhotopheresisPhotopheresis• SteroidsSteroids• Mycophenolate motefilMycophenolate motefil• CSP-A, FK506CSP-A, FK506• Tyrosine Kinase inhibitorsTyrosine Kinase inhibitors

Suppression of allogeneic T cell proliferation Suppression of allogeneic T cell proliferation by donor CD4by donor CD4++CD25CD25++ cells cells

C57Bl/6 (H-2b) → BALB/c (H-2d) TCD BM alone (■) TCD BM plus donor luc+ Tcon alone (left)TCD BM + Tcon (○) TCD BM plus donor Treg + luc+ Tcon (right) TCD BM + Tcon and Treg (●)

From Edinger et al. Nature Medicine, Vol. 9, 2003

Infusion of Treg prior to Tcon enhances GVHD suppressionInfusion of Treg prior to Tcon enhances GVHD suppression

Tumor clearance is not suppressed in Treg recipientsTumor clearance is not suppressed in Treg recipients

From Nguyen et al. Blood, Vol. 109, 2007

Other Ongoing Treg TrialsOther Ongoing Treg Trials

M. Martelli, et al (Perugia)M. Martelli, et al (Perugia)• CD25-enriched Donor Apheresis (haploidentical related BMT)CD25-enriched Donor Apheresis (haploidentical related BMT)

J. Bluestone (UCSF)J. Bluestone (UCSF)• CD24+CD25hiCD127dim sorting + expansion (autologous for Type 1 CD24+CD25hiCD127dim sorting + expansion (autologous for Type 1

Diabetes)Diabetes)

B. Blazar (Minn.) B. Blazar (Minn.) • CD25-enriched with expansion (mismatched unrelated allogeneic BMT)CD25-enriched with expansion (mismatched unrelated allogeneic BMT)

Project goals:Project goals:

• Select Treg to high puritySelect Treg to high purity

• Administer donor regulatory T cells (Treg) to minimize GVHD without Administer donor regulatory T cells (Treg) to minimize GVHD without losing beneficial effects, especially GVLlosing beneficial effects, especially GVL

• Engineer donor grafts to include specific doses of Treg and Tcon Engineer donor grafts to include specific doses of Treg and Tcon without using cell expansionwithout using cell expansion

• Prepare Treg in accordance with regulatory standardsPrepare Treg in accordance with regulatory standards

• Conduct dose escalation study up to 3x10Conduct dose escalation study up to 3x1066 Treg/kg recip. body weight Treg/kg recip. body weight

• Phase 1/2 safety and feasibility trialsPhase 1/2 safety and feasibility trials

Application of Treg in BM TransplantationApplication of Treg in BM Transplantation

Transmissible disease risk – Transmissible disease risk – Donor evaluationDonor evaluation Reagent sourcing, Reagent sourcing,

non-cGMP monoclonal antibodies non-cGMP monoclonal antibodies

Microbial contamination – Microbial contamination – Exposure during “open air” processingExposure during “open air” processing Sterility of reagents and excipientsSterility of reagents and excipients Sterility of sorter fluid pathwaySterility of sorter fluid pathway

Product purity – Product purity – Endotoxin exposureEndotoxin exposure

Product stability – Product stability – Affect of cryopreservation and thawing on cellAffect of cryopreservation and thawing on cell

Functionality of sorted cells –Functionality of sorted cells – Potency assay predictive of GVHD riskPotency assay predictive of GVHD risk

Unlicensed devices – Unlicensed devices – CliniMACS currently operated under IDE for CliniMACS currently operated under IDE for most applicationsmost applications

Influx sorter not used in a prior clinical trial(s)Influx sorter not used in a prior clinical trial(s)

Regulatory concernsRegulatory concerns

CD25 CliniMACS selection from mobilized peripheral CD25 CliniMACS selection from mobilized peripheral blood enriches for FoxP3blood enriches for FoxP3+ + Treg cells Treg cells

CD4 FITC CD25 PE-Cy7

Ungated Ungated CD4 gated (CD4 gated)

FoxP

3 A

lexa

-647

FoxP

3 A

lexa

-647

SS

C

SS

C

CD34 depleted LP CD25 selected cells

32

Most CD25Most CD25++ FoxP3 FoxP3++ cells are CD127 cells are CD127dimdim

Further Treg enrichment requires an additional markersFurther Treg enrichment requires an additional markers

Can use only CD4 and CD127 as sorting markers on CD25-Can use only CD4 and CD127 as sorting markers on CD25-enriched PBMC to obtain high-purity Tregsenriched PBMC to obtain high-purity Tregs

Source of materialsSource of materials Antibodies Antibodies

Sheath fluidSheath fluid Collection/storage medium and additivesCollection/storage medium and additives

Staining preparation for large scale sortStaining preparation for large scale sort Fluorochrome selection/toxicityFluorochrome selection/toxicity

Open container risksOpen container risks

Cell sortingCell sorting GatingGating Sort speedSort speed

Abort rateAbort rate Instrument stabilityInstrument stability Sterility of fluidics Sterility of fluidics Open container risksOpen container risks

QC assaysQC assays Immunophenotyping with FoxP3 (intracellular expression)Immunophenotyping with FoxP3 (intracellular expression) MLR suppression (in vitro assay)MLR suppression (in vitro assay)

Clinical scale cell sorting: Cell processing concernsClinical scale cell sorting: Cell processing concerns

High speed cell sorting for clinical applicationsHigh speed cell sorting for clinical applications

InFluxInFlux FACSAriaFACSAria

IlluminationIllumination Stream in airStream in air Flow cellFlow cell

Ease of useEase of use Need highly trained, dedicated Need highly trained, dedicated operatoroperator

Rapid user training due to Rapid user training due to automationautomation

FluidicsFluidics Totally InterchangeableTotally Interchangeable FixedFixed

Sheath sourceSheath source Hangable BagsHangable Bags Tanks with dip sensorsTanks with dip sensors

Sample lineSample line Replaced with fluidicsReplaced with fluidics FixedFixed

Patient cross-Patient cross-contaminationcontamination

Minimal Minimal High potentialHigh potential

Lymphocyte Sort Lymphocyte Sort RateRate

~20,000/s~20,000/s ~20,000/s~20,000/s

Set upSet up ManualManual AutomatedAutomated

AlignmentAlignment Manual with cells or beadsManual with cells or beads BeadsBeads

Drop delayDrop delay Manual with cells or beadsManual with cells or beads Accudrop beads (Automated)Accudrop beads (Automated)

High speed cell sorting for clinical applicationsHigh speed cell sorting for clinical applications

Influx Cell Sorter -Influx Cell Sorter -

Developed by Cytopeia, Inc (Seattle, WA); manufactured by BD Developed by Cytopeia, Inc (Seattle, WA); manufactured by BD Immunocytometry Systems (San Jose, CA)Immunocytometry Systems (San Jose, CA)

• Lymphocyte Sort rate: 20,000 events/sec (Lymphocyte Sort rate: 20,000 events/sec (~~ 70x10 70x1066/hr)/hr)

• Efficiency: Efficiency: >> 80% recovery of target cells 80% recovery of target cells

• Abort rate: currently <10% Abort rate: currently <10%

• Cell viability: > 95%Cell viability: > 95%

• Class II certifiable HEPA enclosureClass II certifiable HEPA enclosure

• Containment of instrument to maintain aseptic environmentContainment of instrument to maintain aseptic environment• Replaceable fluid pathway includes nozzle assembly, sample line, sheath linesReplaceable fluid pathway includes nozzle assembly, sample line, sheath lines• IDE-grade Miltenyi CliniMACS PBS as sheathIDE-grade Miltenyi CliniMACS PBS as sheath• Sheath line adapter with spikeSheath line adapter with spike

Preventing contamination of sorted cellsPreventing contamination of sorted cells

InFlux Interchangeable Fluidics InFlux Interchangeable Fluidics

Available packaged and Gamma-irradiatedAvailable packaged and Gamma-irradiated DMF availableDMF available Manufacturer DocumentationManufacturer Documentation

Completing the closed fluidics pathCompleting the closed fluidics path

In-house Spike AdapterIn-house Spike Adapter•Tubing and connectors validated Tubing and connectors validated for human usefor human use•Documentation and SOPsDocumentation and SOPs•Integrity testingIntegrity testing•EtO sterilization by ISO 13485-EtO sterilization by ISO 13485-certified CMOcertified CMO•Initial and long-term sterility and Initial and long-term sterility and endotoxin testing programendotoxin testing program

InFlux Interchangeable Fluidics InFlux Interchangeable Fluidics

Pouring buffer into tank not good idea for aseptic sortingPouring buffer into tank not good idea for aseptic sorting

How is the Influx set up?How is the Influx set up?

Currently no GMP-grade calibration or drop delay beadsCurrently no GMP-grade calibration or drop delay beads

SOSO

Validated processes and SOPs were created for:Validated processes and SOPs were created for:

Manual stream alignmentManual stream alignment

Manual laser/scatter alignment with pt cellsManual laser/scatter alignment with pt cells

Drop frequency/Piezo/PressureDrop frequency/Piezo/Pressure

Manual drop delay process with pt cellsManual drop delay process with pt cells• Drop deposition onto AO-coated slideDrop deposition onto AO-coated slide

Points to Consider in the Manufacture and Testing of Monoclonal Antibody Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use (1997)Products for Human Use (1997)

““As a general guidance, we recommend that each purification protocol include at As a general guidance, we recommend that each purification protocol include at least two orthogonal (i.e. based on different mechanisms) robust virus removal least two orthogonal (i.e. based on different mechanisms) robust virus removal steps (see below). Including these steps would not obviate the need for virus steps (see below). Including these steps would not obviate the need for virus clearance studies, except in the case of products intended for use in feasibility clearance studies, except in the case of products intended for use in feasibility trials in serious or life-threatening conditionstrials in serious or life-threatening conditions”.”.

Problem: No GMP-grade Mab reagents available at start of initial Treg trialProblem: No GMP-grade Mab reagents available at start of initial Treg trial

Solution: Solution: CD4 and CD127 Mab engineering run material made CD4 and CD127 Mab engineering run material made available from vendoravailable from vendorRepurify with FDA approvalRepurify with FDA approvalUse until GMP Mabs availableUse until GMP Mabs available

Monoclonal antibody reagents for cell sortingMonoclonal antibody reagents for cell sorting

Monoclonal antibody in PBS by manufacturer

Ig purification by Protein A chromatography

Low pH elution with 0.1M Citric Acid, pH 2.5

pH adjustment to 3.5 with sterile Na-Citrate, 1 hour hold

Neutralization with sterile Na-Citrate

Viral load reduction by passage through Viresolve NFP capsule filter

Succinimidyl ester mediated conjugation of Ig with fluorochrome

Separation of labeled Ig from unbound fluorochrome by Sephadex chromatography

Concentration of conjugated antibodies by UFDF to 200 micrograms/ml

Sterile filtration (0.22 μm), aliquot and freeze (-86°C)

Purity testing:- Western Blot analysis ((≥ 95% IgG)- Protein A concentration (≥ 0.2 mg/ml)

Sterility testing compliant with USP <71>

Specificity and fluorescence intensity assessment by flow cytometry

Ultrafiltration/diafiltration with sterile PBS

Endotoxin by LAL (< 5 EU/ml)

Monoclonal reagent repurification processMonoclonal reagent repurification process

In Process TestingIn Process Testing

• Purity: SDS-PAGE on purified antibodyPurity: SDS-PAGE on purified antibody Residual Protein A testingResidual Protein A testing

• Viral Clearance testingViral Clearance testing

1)1) A Amplification on mplification on Mus dunniMus dunni cells; supernatant co-culture cells; supernatant co-culture withwith PG4 S+L- cellsPG4 S+L- cells 2) Co-incubation with cell lines MRC-5, VERO, NIH 3T3; 2) Co-incubation with cell lines MRC-5, VERO, NIH 3T3; assess hemadsorption, hemagglutination and cytopathic changes assess hemadsorption, hemagglutination and cytopathic changes

Final Product TestingFinal Product Testing

• Sterility: TSB/FTM culturesSterility: TSB/FTM cultures

• Purity:Purity: Endotoxin by LAL Kinetic Chromogenic Assay Endotoxin by LAL Kinetic Chromogenic Assay

•FBS - Unable to trace all exposure; informed consent of recipient requiredFBS - Unable to trace all exposure; informed consent of recipient required

•10 mg each Mab at start, formulated 1 mg after processing and testing10 mg each Mab at start, formulated 1 mg after processing and testing

Monoclonal reagent release testingMonoclonal reagent release testing

Infused fluorochrome estimates for sorted TregInfused fluorochrome estimates for sorted Treg

Fluorochrome MESF Moles/106 Cells Mol. Wt. Maximum Expected Exposure (/kg)

FITC 7000 1.2x10-14 336 g/mole 11.7 picograms

Alexafluor 647 1500 2.5x10-15 1250 g/mole 9.3 picograms

Based on expected maximum dose of 3x10Based on expected maximum dose of 3x106 6 Treg/kg recipient body weightTreg/kg recipient body weight

Limiting fluorochrome exposure from infused TregLimiting fluorochrome exposure from infused Treg

Unstained Unstained

Treg Sort GatingTreg Sort Gating

Consistency of sorted cells over prolonged sort (6 hours) Consistency of sorted cells over prolonged sort (6 hours)

Fraction 1 Fraction 1 Fraction 2 Fraction 2 Fraction 3Fraction 3 Fraction 4 Fraction 4

Suppression of MLR proliferation with freshly sorted TregSuppression of MLR proliferation with freshly sorted Treg

RJA.20080122.A.0001.fcs PB11584 R Proliferation

FL1: CFSE

Cou

nt

100 101 102 103 1040

25

49

74

98

0.00 Division index1.00 proliferattion index0.00 %divided

RJA.20080122.A.0061.fcs T11582:R11584:SJR 1:10.1

Proliferation

FL1: CFSEC

ount

100 101 102 103 1040

81

161

242

322


RJA.20080122.A.0055.fcs T11582:R11584:SJR 1:2.1

Proliferation

FL1: CFSE

Cou

nt

100 101 102 103 1040

102

205

307

409


RJA.20080122.A.0052.fcs T11582:R11584:SJR 1:1.1

Proliferation

FL1: CFSE

Cou

nt

100 101 102 103 1040

90

179

269

358


RJA.20080204.A.0048.fcs R584: StimJR 1:1

Proliferation

FL1: CFSE

Cou

nt

100 101 102 103 1040

39

78

116

155


unstimulated responders stimulators + responders (1:1)unstimulated responders stimulators + responders (1:1)

responders : Treg in suppression assays (stimulators + responders at 1:1)responders : Treg in suppression assays (stimulators + responders at 1:1) 1:1 1:1 1:2 1:2 1:10 1:10

Thawed Treg suppresses MLR proliferationThawed Treg suppresses MLR proliferation

RJA.20080204.A.0056.fcs R582

Proliferation

FL1: CFSE

Cou

nt

100 101 102 103 1040

51

103

154

205

RJA.20080204.A.0047.fcs R584: StimJR 1:1

Proliferation

FL1: CFSE

Cou

nt

100 101 102 103 1040

34

69

103

137


R584:T582:StimJR 10:1 Proliferation

*FL1: CFSE

Cou

nt

100 101 102 103 1040

91

182

273



FL1: CFSE

Cou

nt

100 101 102 103 1040

85

169

254



FL1: CFSE

Cou

nt

100 101 102 103 1040

17

33

50

66


n = 7Length of storage

Pre-freeze viability

Post-thaw viability

Mean 28 weeks 94% 83%

Min. 2 weeks 92% 69%

Max 53 weeks 98% 89%

Antibodies for Selection, Sorting and Identity Assessment Antibodies for Selection, Sorting and Identity Assessment

General parameters to consider for antibodies General parameters to consider for antibodies • GMP compliant preparative antibodies GMP compliant preparative antibodies • Antibodies recognizing unique epitopes from preparative absAntibodies recognizing unique epitopes from preparative abs

• Specificity in detecting target antigens Specificity in detecting target antigens • Compatibility with process and other reagents (antigen loss Compatibility with process and other reagents (antigen loss

during fixation, spectral overlap, sensitivity) during fixation, spectral overlap, sensitivity) • ASR (analyte specific reagents) antibodies when available for ASR (analyte specific reagents) antibodies when available for

release analysis. Validate RUO abs for analysis. Commercial release analysis. Validate RUO abs for analysis. Commercial FC controls where appropriateFC controls where appropriate

Examples:Examples:• Use of an independent marker to establish purity (FoxP3 in Treg)Use of an independent marker to establish purity (FoxP3 in Treg)• Use of antibodies recognizing non-cross inhibiting epitopes to Use of antibodies recognizing non-cross inhibiting epitopes to

CD4 for sorting and analysis CD4 for sorting and analysis

FoxP3+ Post-Sort Cell Analysis for Treg PurityFoxP3+ Post-Sort Cell Analysis for Treg Purity

Validated independent Validated independent measurement of CD4 and measurement of CD4 and

FoxP3FoxP3

*CD4 clone L200 for sorting & SK3 for analysis**CD4 clone L200 for sorting & SK3 for analysis**CD25 ab staining blocked by selection reagent**CD25 ab staining blocked by selection reagent*

CD34 depleted PBSCCD34 depleted PBSCCD45+ gatedCD45+ gated

CD25CD25++ Enriched Enrichedungatedungated

CD4CD4+ + CD127CD127lowlow Sorted SortedCD45+ gatedCD45+ gated

CD25 CD25 SelectionSelection

CD4+CD127lowCD4+CD127lowSortingSorting

GMP grade sorting Mabs GMP grade sorting Mabs validatedvalidated

ASR CD45, CD3, CD4 ASR CD45, CD3, CD4 detection abs validated on detection abs validated on commercial FC controlscommercial FC controls

Apheresis collection

CD34 flow-through cells

CD25 selected cellsCD25 flow-through cells

Cryopreservation

• Cell count/viability• Sterility • Flow assessment• CFU assay

• Cell count/viability• Sterility• Flow assessment• CFU assay

CD4+/CD127low cells

CELL SELECTION PRODUCT QC

• Cell count/viability• Sterility• Flow assessment• FoxP3 Assay

CliniMACS CD34 selection

CliniMACS CD25 selection

Flow cytometric cell sorting

HPC for infusion

Tcon for infusion

Treg for infusion

HPC and Treg cell processing for match-related HCTHPC and Treg cell processing for match-related HCT

• Cell count/viability• Sterility• Flow assessment

CD34 selected cells

Application of Treg in Allogeneic BMT: Matched-donor Application of Treg in Allogeneic BMT: Matched-donor HSC/Treg trialHSC/Treg trial

Day -2Day -2

CD34 CliniMACS Selection CD34 CliniMACS Selection

Day -1Day -1

CD4+CD127din Treg CD4+CD127din Treg sortingsorting

Day 0Day 0

Release testingRelease testing

CD34+HSC , Treg InfusionCD34+HSC , Treg Infusion

Day -3,2Day -3,2

Donor ApheresisDonor Apheresis

G-CSF-MobilizedG-CSF-Mobilized

Infusion Release Criteria:Infusion Release Criteria:EndotoxinEndotoxinFoxP3%FoxP3%ViabilityViabilityCell Count/DoseCell Count/DoseSterility (Gram stain)Sterility (Gram stain)

Reportable Data:Reportable Data:14-day sterility14-day sterilityAncillary phenotyping by flowAncillary phenotyping by flowMLR inhibitionMLR inhibition

Day +3Day +3

Tcon InfusionTcon InfusionDay -10Day -10

Recipient conditioningRecipient conditioning

Application of Treg in treatment of chronic or acute GVHDApplication of Treg in treatment of chronic or acute GVHD

Day -2Day -2

CD25 CliniMACS Selection CD25 CliniMACS Selection

Day -1Day -1

CD4+CD127din Treg CD4+CD127din Treg sortingsorting

Day 0Day 0

Release testingRelease testing

Treg InfusionTreg Infusion

Day -3,2Day -3,2

Donor ApheresisDonor Apheresis

Non-MobilizedNon-Mobilized

Infusion Release Criteria:Infusion Release Criteria:EndotoxinEndotoxinFoxP3%FoxP3%ViabilityViabilitySterility by Sterility by Gram stainGram stainCell CountCell CountDoseDose

Reportable Data:Reportable Data:14-day sterility14-day sterilityAncillary phenotyping by flowAncillary phenotyping by flowMLR inhibitionMLR inhibition

Thawed Treg Thawed Treg InfusionInfusion

Sorting of CD4+/CD127Sorting of CD4+/CD127lowlow cells improves purity of Treg cells improves purity of Treg compared to CD25+ enrichmentcompared to CD25+ enrichment

Post-CD25 enrichment Post-CD25 enrichment mean = 77.2% FoxP3+mean = 77.2% FoxP3+

Post-CD4+CD127Post-CD4+CD127lowlow sort sort mean = 95.3% FoxP3+mean = 95.3% FoxP3+N=32N=32(p=0.003)(p=0.003)

Regulatory T-cell (Treg) Isolation ProcessRegulatory T-cell (Treg) Isolation Process

Prophylaxis and treatment of Graft vs. Host Disease in Prophylaxis and treatment of Graft vs. Host Disease in BMT patientsBMT patients

TTandem selection approach:andem selection approach: Clinical-scale CD25 immunomagnetic bead Clinical-scale CD25 immunomagnetic bead

enrichmentenrichment High-speed FACS-based Treg enrichment by High-speed FACS-based Treg enrichment by

CD4+CD127CD4+CD127lowlow phenotype (Vendor supplied reagents) phenotype (Vendor supplied reagents) Isolate therapeutic target doses of naturally occurring Isolate therapeutic target doses of naturally occurring

Treg (>1X10Treg (>1X1066/kg to 3X10/kg to 3X1066/kg)/kg) Validated reagents for independent verification of Treg Validated reagents for independent verification of Treg

content for product releasecontent for product release Vendor initiated internal GMP Mab quality processVendor initiated internal GMP Mab quality process

AcknowlegementsAcknowlegements

Our Stanford BMT Patients & Their FamiliesOur Stanford BMT Patients & Their Families

Stanford BMT Cellular Therapy FacilityStanford BMT Cellular Therapy FacilityCynthia Tudisco Cynthia Tudisco Gina Monterola Gina Monterola Keri Tate, PhDKeri Tate, PhDMary McLeodMary McLeod Kevin Sheehan, PhDKevin Sheehan, PhD Stanford Blood & Marrow Transplantation ProgramStanford Blood & Marrow Transplantation ProgramRobert Negrin, MD; Program ChairRobert Negrin, MD; Program Chair Ginna Laport, MD Ginna Laport, MDDavid Miklos, MD, PhD Judith Shizuru, MD, PhDDavid Miklos, MD, PhD Judith Shizuru, MD, PhD

Stanford HealthcareStanford HealthcareDavid DiGiusto, PhD. - Executive Director of Stem Cell and David DiGiusto, PhD. - Executive Director of Stem Cell and Cellular Therapy OperationsCellular Therapy Operations

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Treg InFlux present