ApoptoSENS - Senolytic CAR-NK Cells
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ApoptoSENS - Senolytic CAR-NK Cells

Senescence
CAR-NK Cells
Ageing
Senescent cells accumulate with age and are associated with numerous diseases. Dr. Amit Sharma’s team have identified senescence-specific cell surface biomarkers which will act as targets for developing Chimeric Antigen Receptor Natural Killer (CAR-NK) cells aiming to precisely and safely eliminate senescent cells in vivo.
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Investment
$ 253,000
Initiated
25.4.2022
Approval
100% Voted Yes
Project Details
Dr. Amit Sharma
Research Lead
AT A GLANCE
Stage
Early stage preclinical discovery
Area
Chimeric Antigen Receptor Natural Killer (CAR-NK) cells
Status
Ongoing
Patent
Pending

Background

Cellular senescence is the irreversible arrest of proliferation associated with a proinflammatory phenotype that can lead to tissue dysfunction and is implicated in numerous diseases. Natural Killer cells have an innate ability to remove senescent cells, however immune evasion can occur which contributes to an accumulation of senescent cells with age. Several genetic and pharmacological studies have shown that elimination of senescent cells can ameliorate hallmarks of aging in both mice and humans, however more specific therapeutic interventions are required.

Aims, Hypothesis & Results

Dr. Amit Sharma is developing Chimeric Antigen Receptor Natural Killer (CAR-NK) cells to precisely and safely eliminate senescent cells in vivo. The team have identified a number of senescence-specific surface markers which could be targeted for senescence removal. They will focus on their most promising candidate senescent cell markers which will be more extensively validated using additional cell model paradigms (stressors), as well as in mouse models (cross-species validation). Validated surface markers will be used to generate monoclonal antibodies, which will then be confirmed for specificity against the target antigen. Appropriate CAR-NK cells will be created to further establish proof-of-concept for their approach of selective removal of senescent cells in their various model systems.

Timeline

Pre-Clinical Studies: Monoclonal antibody generation, cloning and expression of lentiviral vectors, and CAR-NK cell generation.

Required Funding: $430,000 (VitaDAO providing $253,000)
Status: Ongoing
Duration: 24 Months

VitaDAO Board Evaluation Writeup

Dr. Amit Sharma has a strong scientific background in senescence and is based at the SENS Research Foundation which provides strong support with a track record of successful spin-outs (eg Underdog Pharma 1). The removal of senescence cells is an attractive therapeutic approach to combat aging and promote longevity. Data from Dr. Sharma’s team and others showing NK cell cytotoxicity towards senescent cells provides proof-of-concept that using CAR-NK cells is a feasible strategy to eliminate senescent cells. The team’s identification of senescence-specific cell surface markers in vitro is extremely promising and if these markers are also expressed in senescent cells in vivo, this has the potential to be an effective senolytic therapy. 

Latest Project Updates
13
September
2022
13
September
2022
VitaDAO IP-NFT Transfer Ceremony with Molecule & ApoptoSENS

The vote has passed, the decision is made: ApoptoSENS will be the 5th research organisation to fund their longevity research via an IP-NFT.

25
April
2022
Project Initiated!

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