Development of pancreatic cancer targeting aptamer and therapeutic - - PowerPoint PPT Presentation

CHOI SUN IL

National Cancer Center, Korea JP BIO A Corporation, Korea

Development of pancreatic cancer targeting aptamer and therapeutic application

[Background of Study]

Apta ptamer mer is is “nucleic ac acid id antibody”

Definition Single-stranded oligonucleotide molecules Affinity High (pM – nM) specificity High Material Nucleic acid

(long-termstability as dry powder or in solution)

Production In vitro Chemical process Target Wide range of target

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

Batch to batch variation Little or no Modification Easy and straightforward : site-specific modification possible Size 20 kDa Penetration Fast tissue penetration 3D structure formation

Target binding Binding mechanism

• Structure compatibility
• Electrostatic interaction

A A CAAT AGA G A A A G T A G AATAC A A A A A A G T

Aptamer sequence

Target

• Aptamer selection process : SELEX

(Systematic Evolution of Ligands by Exponential enrichment)

Objec Objectiv tive of

• f study

study To

• de

develop elop apta ptamer mer-ba based sed the therape peutics utics wi with th high high spe specifi cificity and city and ef effi fica cacy for

• r pa

panc ncrea eatic tic ca canc ncer er

 The he str strate tegy of

• f Doli

Doligob gobody

• dy (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 Cell-SELEX SELEX for

• r pancr

pancrea eatic tic cancer cancer specific specific aptamer ptamer

C D

20 μ Normal cells (HPNE) Target cells (CMLu-1) 20 μm H&E Library SQ7 SQ6 SQ9 SQ8

1-2. Siz Size-op

• ptim

timiza ization tion of

• f SQ

SQ7 : SQ SQ7-1 (32 32 nt nt)

SQ7 aptamer structure-based size minimization to SQ7-1 SQ7-1 aptamer internalizing into CFPAC1 cells

• 2. Aptamer

ptamer-antibody antibody comple complex (Oligobo Oligobody dy)

• 3. Dr

Drug ug-conjuga conjugated ted Oligobo Oligobody dy (DO DOligobody ligobody)

Su Summar mmary

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.

CO CONC NCLS LSIO ION De Develop elopmen ment of t of apta ptamer mer-ba based sed the therape peutics utics for

• r pa

panc ncrea eatic tic ca canc ncer er

Lysosome

(CathepsinB)

Drug is released into the cytoplasm

Cell death High High ef efficac ficacy → Cell death High High spec specificity ificity High High af affinity finity High Higher er sta stabili bility ty High Higher er pe pene netr tration tion

Ac Ackn knowl wled edge gemen ment

<Ad <Advi visor> sor>

* * Dr. . Yun un-Hee Hee Kim Kim, , NC NCC, , GC GCSP SP

<Lab me memb mbers> rs>

Yu Yu-Sun un Lee, N Lee, NCC CC Joon K

• on Ki

i Kim, im, NCC CC Be Benja njamin min, , NCC CC Mi i rim rim Lee, N Lee, NCC CC

<Aptame tamer> r>

Dr Dr. . In-Hoo

• o Kim,

im, NCC CC, , GCS CSP Dr Dr. . Kyun un Heo eo, , NCC CC Dr Dr. . Youn

• un Hoon
• on Joo
• o, JP

, JP BIO BIO A C A Co. Dr Dr. . Junho unho Chung, Chung, SNU Hyun un Jung ung Kim, im, NCC CC Yul ul Min in Lee Lee, N , NCC CC, , JP JP BIO BIO A

<Flow w cyto ytome metr try & y & Confoc focal analys ysis> s>

Tae ae Sik ik Kim, Kim, NCC NCC Mi i Ae K Ae Kim, im, NCC CC

<Anima mal experi rime ment t & & ti tiss ssue patho thology> y>

Mi i Sun un Par ark, k, NCC CC Bo Bo Ra K Ra Kim, im, NCC CC