Therapeutic antibodies-

TUTORIAL
Kuby (6e) Chapters 4, 5, 22
Roitts Immunology (7e) Chapter
!herapeuti" m#bs

Comprise the ma$ority o% biote"hnology&base'

me'i"ines sent to "lini"al trials

24 li"ense' m#bs

(n"ology

Chroni" in%lammatory "on'itions

!ransplantation

In%e"tious 'isease

Car'io)as"ular 'isease
!herapeuti" mo'es o% a"tion
Blocking:

#ntagonisti" or neutralising a"ti)ity

Agonistic:

*imi" a"tion o% en'ogenous ligan's

Activating:

Re"ruit immune systems e%%e"tor %un"tions

Conjugated:

#"t as 'eli)ery )ehi"les %or therapeuti" "on$ugates (e+g+

ra'ioa"ti)e isotope or 'rug)
#nti&C,2- m#bs
Ritui!ab (Ritu.an/)

Chimeri" Ig01 m#b

2se' to treat 3&"ell malignan"ies an' autoimmune 'iseases

4romotes #,CC an' C,C& a"ti)ating

5ost e%%e"tor systems "oul' be"ome 6o)erloa'e'

Tositu!o!ab (3e..ar/)

*urine Ig02a m#b "on$ugate' to io'ine&11

*ouse m#bs ha)e short hal%&li%e in humans, so si'e&e%%e"ts

o% ra'iotherapy re'u"e'
#nti&708R m#bs
"erceptin# (trastu9umab)

5umanise' Ig01

3in's 5er&2 (7rb32) : epi'ermal gro;th %a"tor re"eptor %oun'

on some tumour "ells (breast "an"ers<lymphomas)

!he only m#b so %ar that seems to be e%%e"ti)e against soli'

tumours

3ut only e%%e"ti)e against "an"ers e.pressing )ery high le)els

o% 5er&2

=eems to ;or> by blo">ing me"hanisms an' a"ti)ating #,CC

#nti&!?8@ m#bs
Adali!u!ab

4hage 'isplay&'eri)e' m#b

?eutralises !?8@ & blo">ing

#ppro)e' %or R#, Chrohns 'isease an' psoriasis

#nti&'rug #b responses in 14&A7B patients

5uman i'iotypes potentially immunogeni"

(ther %a"tors "an C immunogeni"ity ('osing, route o%

a'ministration, "on"omitant treatment et")
*ylotarg : immunoto.in
*ono"lonal antibo'y against a"ute myelogenous leu>emia
(A$L)
anti&C, "on$ugate' ;ith calichea!icin, ;hi"h ma>es 's
stran'e' ,?# brea>s
*ylotarg is the %irst anti&"an"er i!!unotoin
C, is not e.presse' by 7= "ells use' to re"onstitute
the bone marro;
?o)el "on$ugation strategies
*ylotarg C,
5er"eptin
!?8
3e.aar C,2-&I11
C,2-
ne% insights in B cell &unctions
!herapeuti" use o% mono"lonal antibo'ies eg
Ritu.imab ("himeri" C,2-) has le' to
Dun' an' Ran'all Nature Reviews Immunology (2-1-)
=hrin>age o% auto&rea"ti)e ! "ell pool
eg Pemphigus vulgaris
resetting o% !h1E !h2 imbalan"es
eg. LCMV eg. nematode H.polygyrus
mR?# %or C,4 C,25 8o.p C!D#&4 0I!R
eg SLE patients vs ontrols! MCV patients! N"#
mie
ID&1- se"reting nai)e repopulating 3 "ells
eg adoptive trans$er in SCI# N"# mie
Ritui!ab treat!ent
New insights
Auto-reactive T cells require B cells to clonally
expand
Th1 cells and Th2 cells are expanded by Be-1 and
Be-2 effector cells respectively
Effector B cells inhibit T reg expansion
!aive" #$-1%& T'() secreting B cells exist* +hich
cause expansion of T regulatory cells
B cells are also needed to ,aintain long-ter, T cell
,e,ory

eg #"ute >i'ney re$e"tion

4re&sensiti9e' people & #b me'iate'

Ritu.imab suppresses re$e"tion

Kno">s out memory<e%%e"tor 3 "ells

?ai)e people% ! "ell me'iate'

Ritu.imab enhances a"ute re$e"tion

Kno">s out nai)e 63 reg

Ritui!ab treat!ent &or transplant rejection can enhance
or inhibit rejection' (e !a) no% understand %h)'
*iagnostics:
+athogens ,
Tu!ours
I!aging
I!!unotherap)
e vivo
I!!unotherap)
in vivo
+regnanc)
testing
Blood drug testing
$atching
histoco!patibilit) Ags-
blood grouping.
transplantation
2ses %or
*ono"lonal
#ntibo'ies