Immunology MAb b

8/18/2019 Immunology MAb b

1/25

I. Overview: - The Immune SystemII. Introduction: - Monoclonal

Antibodies

Medical Information ServicesDr Rucha Ponkshe Ms Anahita GouriSenior Manager - Medical Information Executive – Medical Information


2/25

• Goal : - To develop a basic foundation of how theimmune defenses operate in order to understand the

science behind Monoclonal Antibodies

•Strategy : - To focus on the big Picture !ot thedetails

• Problem: - Too much information to be compressed

• "hat we have done to help #: -

• Monoclonal Antibody $older on % colon & $'A 'ocuments& (ist of mA) with %nternational P%& *+clusive database on Abci+imab and %nfli+imab& Presentation with ,ey concepts identified


3/25

• The Perfect "orld • The .eal "orld

COLD

L

!

C"IC#$%

&O'

ST/MA01 2PS*T

"$L&M$ (

"$L& (

"$L&

M$(


4/25

T"$ IMM!%$ S)ST$M

D$ I%ITIO%: - The inte*rated body system o+ or*ans, tissues,cells cell roducts that di++erentiates sel+ +rom non / sel+ neutrali0es otentially atho*enic or*anisms.(The American Heritage Stedman's Medical Dictionary)

The Latin term “IMMUNIS” means $'$M&T, re+errin* torotection a*ainst +orei*n a*ents.

The Immune System consists o+1. Innate Immunity &rimary 2es onse

3. Ac4uired Immunity Secondary 2es onse


5/25

A%ATOM) O T"$ IMM!%$ S)ST$M


6/25

C$LLS O T"$ IMM!%$ S)ST$M


7/25

5$COM$S

!%CTIO%I%6 O T"$ IMM!%$ S)ST$M12M/.A( 3A!T%)/'4 M*'%AT*'5 %MM2!* .*SP/!S* 0*(( M*'%AT*' %MM2!* .*SP/!S*

A!T%G*! 36 ST *7P/S2.*5

A%TI6$%SDIS&LA)$D5)I% $CT$DC$LLSACTI7AT$

C)TOTO'ICT C$LL

6I7$S 2IS$ TO

ACTI7$C)TOTO'IC TC$LL

$%6!L $D 5)

STIM !LAT$S

MA0./P1AG*

A&C

"$L&$2T C$LLS STIM!LAT$S

M$MO2)"$L&$2 TC$LLS

M$MO2)T C$LLS

M$MO2)5 C$LLS

&LASMAC$LLS

STIM!LAT$S STIM!LAT$S

5 C$LLS

2$$A%TI6$%SDI2$CTL)ACTI7AT$

STIM!LAT$S

6I7$S 2IS$ TO

S$C2$T$ A%TI5ODI$S

STIM!LAT$S

A!T%G*! 38 nd *7P/S2.*5

STIM!LAT$S

'e f end against e+tracellular pathogens by binding toantigens and ma,i ng them easier tar gets for ph agocytes

and com plem ent

' ef end against intracellu lar pathogens and cancer by binding and lysing the infected cells or cancer cells


8/25

IMM!%OT"$2A&)

Treatment o+ the disease by Inducin*, $nhancin* orSu ressin* the Immune System.

Active Immunothera y: -

It stimulates the body8s ownimmune system to +i*ht thedisease.

&assive Immunothera y: -

It does not rely on the body toattac9 the disease, instead theyuse the immune systemcom onents such asantibodies; created outside thebody.


9/25

"ISTO2) O IMM!%OLO6)

•1862 Ernst Haeckel, Recognition of phagocytosis

•1877 Paul Erlich, recognition of mast cells •1879 ouis Pasteur, !ttenuate" chicken cholera #accine"e#elopment

•188$ Elie %etchnikoff &ellular theory of #accination

•188' ouis Pasteur, Ra(ies #accination "e#elopment

•1888 Pierre Rou) * !le)an"re +ersin, acterial to)ins

•1888 -eorge .uttall, acterici"al action of (loo"

•1891 Ro(ert /och, 0elaye" type hypersensiti#ity

•189 Richar" Pfeiffer, acteriolysis

•189' ules or"et, &omplement an" anti(o"y acti#ity in(acteriolysis

•1933 Paul Erlich, !nti(o"y formation theory

•1931 /arl an"steiner, !, an" 4 (loo" groupings

•193158 &arl ensen * eo oe(, ransplanta(le tumors

•1932 Paul Portier * &harles Richet, !naphyla)is

•193$ !lmroth right * te art 0ouglas, 4psoni:ation reactions

•1936 &lemens #on Pir;uet, coine" the or" allergy

•1937 #ante !rrhenius, coine" the term immunochemistry

•1913 Emil #on 0ungern, * u" ik Hirs:fel", agraeus, 0emonstration of anti(o"ypro"uction in plasma cells

•19 8 -eorge nell, &ongenic mouse lines

•19 9 %acfarlane urnet * >rank >enner,


10/25

A%TI5ODI$S

ST2!CT!2$ CLASS


11/25

A%TI5ODI$S

Derived +rom di++erent 5Lym hocytes cell lines

&OL)CLO%AL. MO%OCLO%AL.

Derived +rom a sin*le 5 cellclone

5atch to 5atch variationa++ectin* Ab reactivity

titre

mAb o++er 2e roducible,&redictable &otentially

ine


12/25

&2OD!CTIO% O MO%OCLO%AL A%TI5OD)

")52IDOMA T$C"%OLO6)


13/25


Ste 1: - Immuni0ation O+ Mice Selection O+ MouseDonor or 6eneration O+ "ybridoma cells


A%TI6$% Intact cell=

>hole cell membrane=micro-or*anisms ; ?AD@!7A%T

emulsi+ication ;

Ab titre reached in Serum

S leen removed

source o+ cells;


14/25


Ste 3: - Screenin* O+ Mice or Antibody &roduction


A+ter severalwee9s o+

immuni0ation

Serum Antibody Titre Determined

Techni4ue: - $LISA = low cytometery;

Titre too low

5OOST&ure anti*en;

Titre "i*h

5OOST&ure anti*en;

8 wee,s


15/25


Ste : - &re aration o+ Myeloma Cells


Immortal Tumor O+ Lym hocytes

? B - A0a*uanine

Myeloma Cells

"i*h 7iability 2a id 6rowth

"6&2T -

Myeloma Cells


16/25


Ste : - usion o+ Myeloma Cells with Immune S leen Cells

Selection o+ "ybridoma Cells


!SIO%

&$6

M)$LOMA C$LLSS&L$$% C$LLS

")52IDOMA C$LLS$LISA &LAT$

eeder Cells6rowth Medium

"AT Medium

1. &latin* o+ Cells in"AT selectiveMedium

3. Scannin* o+ 7iable"ybridomas


17/25


Ste : - Clonin* o+ "ybridoma Cell Lines by Limitin*DilutionE or $< ansion


A. Clone $ach ?ve Culture

5. Test $ach Su ernatant +or Antibodies

C. $< and ?ve Clones

MouseAscitesMethod

TissueCultureMethod


18/25




19/25

$7OL!TIO% O MO%OCLO%AL A%TI5OD)

6 T.A!SG*!%0

'!A SP(%0%!G 9 G*!* !/0/2T

8 (%).A.%*Sa )A0T*.%/P1AG*

b m.!A

c 0ell Surface


20/25

$%6I%%$2$D A%TI5ODI$S


21/25


22/25

Applications of Monoclonal

Antibodies• 'iagnostic Applications

5iosensors Microarrays• Therapeutic Applications

Trans lant reGection Muronomab-CDCardiovascular disease Abci


23/25

Mar9et Analysis orecast• Industry participants forecast of the market vary

widely, however, a consensus is emerging thatthe market should reach US$26 billion by the endof the decade. his is a conservative estimateimplying an average annual growth rate of !"#.

• y 2%%", m&bs should account for '2 percent ofall revenue in the biotech market

• !%% m&b ()pected y 2%!%

• m&b contributing to the in vitro diagnosticsmarket e)pected to be worth $'* illion this year


24/25

>hy should we be interested H• m&bs drive the development of multibillion dollar

biotechnology industry.

• +any of the leading pharmaceutical companieshave entered the m&b sector, attracted by uickerand less costly development, higher success rates,premium pricing, and a potentially reduced threatfrom generics

• he outlook for monoclonal antibody therapeuticsis healthy. he ongoing success of e)istingproducts, combined with a bulging pipeline of newproducts awaiting approval and limited genericerosion, point towards robust growth in thissegment


25/25

&A!L $"2LIC"“…. I TRUST, THAT

WE NO LONGERFIND OURSELVES

LOST ON ABOUNDLESS SEA,

BUT THAT WEHAVE ALREADY

CAUGHT ADISTINCT GLIMPSE

OF THE LANDWHERE WE HOPE,

NAY, WHICH WE

EXPECT, WILLTEILD RICHTREASURES FOR

BIOLOGY ANDTHERAPEUTICS ”

Immunology MAb b

Documents

Transcript of Immunology MAb b