Treatment of HIV and acute myeloid leukemia by allogeneic CCR5-d32 - - PowerPoint PPT Presentation

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Aug 23, 2022 145 likes •402 views

Treatment of HIV and acute myeloid leukemia by allogeneic CCR5-d32 blood stem cell transplantation Elena Knops Elena Knops, GfV 2016 Background - the Berlin patient so far the only person presumed to be cured from HIV by hematopoietic

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Elena Knops, GfV 2016

Treatment of HIV and acute myeloid leukemia by allogeneic CCR5-d32 blood stem cell transplantation

Elena Knops

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Elena Knops, GfV 2016

Background

the Berlin patient – so far the only person presumed to be cured from HIV by

hematopoietic stem cell transplantation (HSCT) from a homozygous CCR5-d32 donor

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Elena Knops, GfV 2016

Background

the Berlin patient – so far the only person presumed to be cured from HIV by

hematopoietic stem cell transplantation (HSCT) from a homozygous CCR5-d32 donor

failed attempts to reproduce cure by HSCT - viral rebound or death due to

underlying malignancy

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Elena Knops, GfV 2016

Background

the Berlin patient – so far the only person presumed to be cured from HIV by

hematopoietic stem cell transplantation (HSCT) from a homozygous CCR5-d32 donor

failed attempts to reproduce cure by HSCT - viral rebound or death due to

underlying malignancy

THE question about all of these attempts and the Berlin patient:

How to be sure about the cure? Is there any virus in the patient?

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Elena Knops, GfV 2016

The whole story (drama in 4 acts)

46y old patient alive, well and undetectable for HIV (RNA/DNA) over 3 years after allogeneic CCR5-d32 HSCT

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Elena Knops, GfV 2016

The beginning (prologue)

induction consolidation

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Elena Knops, GfV 2016

The beginning (prologue)

induction consolidation

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Elena Knops, GfV 2016

The beginning (prologue)

induction consolidation

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Elena Knops, GfV 2016

Chapter I

.... ....

ne week before

SCT

female donor, 10 out of 10 HLA- matched CCR5-d32

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Elena Knops, GfV 2016

Chapter I

.... ....

ne week before

SCT

female donor, 10 out of 10 HLA- matched CCR5-d32

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Elena Knops, GfV 2016

Chapter I

.... ....

ne week before

SCT

female donor, 10 out of 10 HLA- matched CCR5-d32

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Elena Knops, GfV 2016

Chapter I

.... ....

ne week before

SCT

female donor, 10 out of 10 HLA- matched CCR5-d32

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Elena Knops, GfV 2016

Chapter II

....

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Elena Knops, GfV 2016

Chapter II

....

total of 8 courses of 5-azacytidine + 4 donor lymphocyte infusions

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Elena Knops, GfV 2016

Chapter III

....

<LOD (884250) in rectal and ileum biopsy

10 10 10

+ CMV, HHV8, HSV

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Elena Knops, GfV 2016

Chapter III

....

<LOD (884250) in rectal and ileum biopsy

10 10 10

+ CMV, HHV8, HSV

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Elena Knops, GfV 2016

Chapter III

....

<LOD (884250) in rectal and ileum biopsy

10 10 10

Tacrolimus + topical steroids + CMV, HHV8, HSV

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Elena Knops, GfV 2016

Chapter III

....

<LOD (884250) in rectal and ileum biopsy

10 10 10

+ CMV, HHV8, HSV Tacrolimus + topical steroids

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Elena Knops, GfV 2016

Chapter III

....

<LOD (884250) in rectal and ileum biopsy

10 10 10

+ CMV, HHV8, HSV Tacrolimus + topical steroids

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Elena Knops, GfV 2016

Chapter III

....

<LOD (884250) in rectal and ileum biopsy

10 10 10

+ CMV, HHV8, HSV Tacrolimus + topical steroids

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Elena Knops, GfV 2016

02/2013

pos. control
neg. control

06/2014 02/2015 07/2015 12/2015 01/2016

gp160 gp120 gp41 p34 p25 p18 p55 p68

Chapter IV

before SCT

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Elena Knops, GfV 2016

HIV reservoirs

anatomical cellular

GALT
lymph nodes
Liquor/CNS/CSF
urogenital tract
follicular

dendritic cells

macrophages
resting CD4+

cells

„Can HIV be cured?“ Mario Stevenson Scientific American 299, 78 - 83 (2008)

Hide-outs of HIV

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Elena Knops, GfV 2016

The end? (epilogue)

Viral outgrowth assay (EPISTEM: Javier Martinez-Picado, Barcelona):

PBMCs (in progress) and lymph node (planned)

V3 phenotypes of the minority of the predicted X4 variants

(EPISTEM: Monique Nijhuis, Utrecht)

T-cell response assay (Thomas Harrer, Erlangen):

PBMCs (in progress)

proviral DNA load from further PBMC samples, biopsies and lymph nodes

(Institute of Virology, Cologne and Gabor Dunay, HPI, Hamburg)

proviral DNA load from PBMCs from the time points of the AML relapse

(in progress)

European project to guide and investigate the potential for HIV cure by stem cell transplantation.

The EPISTEM project is supported by amfAR Research Consortium

n HIV eradication (ARCHE) Research Grant # 108930-56-RGRL

www.epistem-project.org

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Elena Knops, GfV 2016

The end? (epilogue) Stop ART? What else?

THE question: How to be sure about the cure?

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Elena Knops, GfV 2016

Institute for Immunogenetics, Kaiserslautern

Martin Däumer, Alex Thielen

Heinrich Pette Institut HH

Gabor Dunay, Johanna Eberhardt, Silke Kummer, Julian Schulze zur Wiesch

Med 3, University of Erlangen

Thomas Harrer

MASTER–HIV/HEP (RKI, Resina)

Norbert Bannert, Barbara Bartmeyer, Osama Hamouda, Klaus Jansen, Claudia Kücherer, Andrea Hauser, Robert Koch Institut (RKI), Berlin

Dept. Gastroenterologie, Krankenhaus der Augustinerinnen, Cologne

Mark Oette

MPI of Informatics, Saarbrücken

Thomas Lengauer, Nico Pfeifer, Alejandro Pironti, Prabhav Kalaghatgi

Thanks to our group

Institute of Virology, University of Cologne

Rolf Kaiser Veronica Di Cristanziano Maria Neumann-Fraune Eugen Schülter Claudia Müller Saleta Sierra-Aragon Eva Heger Simon Lennartz Hermann Töpker Max Damagnez Stephanie Inden Sascha Hasheminasab Herbert Pfister

University of Düsseldorf

Hepatology & Infectiology Björn Jensen Falk Hüttig Dieter Häussinger Virology Nadine Lübke Haematology Guido Kobbe Moleculare Medizin Philipp Lang Junnat Hamdam