CHOI SUN IL

National Cancer Center, Korea

JP BIO A Corporation, Korea

Development of pancreatic cancer targeting

aptamer and therapeutic application

[Background of Study]

Aptamer is “nucleic acid antibody”

Definition Single-stranded oligonucleotide molecules

Affinity High (pM – nM)

specificity High

MaterialNucleic acid

(long-termstability as dry powder or in solution)

Production In vitro Chemical process

TargetWide range of target

(protein, sugar, ion, cell, toxins, …)

Batch to batch variation

Little or no

ModificationEasy and straightforward

: site-specific modification possible

Size 20 kDa

Penetration Fast tissue penetration

3D structure formation

Target binding

Binding mechanism

- Structure compatibility

- Electrostatic interaction

AA

CAATAGA

GA

AAG

T

AGAATAC

AA A

AA

A

GT

Aptamer sequence

Target

Aptamer selection process : SELEX(Systematic Evolution of Ligands by Exponential enrichment)

Objective of study

To develop aptamer-based therapeutics

with high specificity and efficacy

for pancreatic cancer

The strategy of Doligobody (Drug-oligomer-antibody complex)

Aptamer

Pancreatic

cancer cell

Antibody(Supporter)

② To enhance the stability

Drug(Payload)

③ To enhance the efficacy

①Specific targeting

and optimization

for modification

1-1. Cell-SELEX for pancreatic cancer specific aptamer

C

D

20 μm

No

rma

l c

ell

s

(HP

NE

)

Ta

rge

t c

ell

s

(CM

Lu

-1) 20 μm

H&E Library SQ7SQ6 SQ9SQ8

1-2. Size-optimization of SQ7 : SQ7-1 (32 nt)

SQ7 aptamer structure-based

size minimization to SQ7-1

SQ7-1 aptamer internalizing

into CFPAC1 cells

2. Aptamer-antibody complex (Oligobody)

3. Drug-conjugated Oligobody (DOligobody)

Summary

VC-MMAE (Payload)

Powerful Cell toxicity

Selective cleavage (Cathepsin B)

Cotinine & Cot-body(Supporter)

Humanized anti-cotinine antibody

Increase pharmacokinetics

Aptamer SQ7-1 (Navigator)

High affinity & specificity

Internalization

DOligobody (Drug + Oligomer + Antibody) has anti-cancer effect.

CONCLSION

Development of aptamer-based therapeutics

for pancreatic cancer

Lysosome(CathepsinB)

Drug is released

into the cytoplasm

Cell

death

High efficacy→ Cell death

High specificityHigh affinity

Higher stabilityHigher penetration

Acknowledgement

<Advisor>

* Dr. Yun-Hee Kim, NCC, GCSP

<Lab members>

Yu-Sun Lee, NCC

Joon Ki Kim, NCC

Benjamin, NCC

Mi rim Lee, NCC

<Aptamer>

Dr. In-Hoo Kim, NCC, GCSP

Dr. Kyun Heo, NCC

Dr. Youn Hoon Joo, JP BIO A Co.

Dr. Junho Chung, SNU

Hyun Jung Kim, NCC

Yul Min Lee, NCC, JP BIO A

<Flow cytometry & Confocal analysis>

Tae Sik Kim, NCC

Mi Ae Kim, NCC

<Animal experiment & tissue pathology>

Mi Sun Park, NCC

Bo Ra Kim, NCC