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ANTIBODI MONOKLONAL FARMASI USB

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 ANTIBODI
▪Merupakan glikoprotein yang dihasilkan oleh
sel B untuk melawan benda asing/antigen/non-
self
▪Imunoglobulin (Ig) atau serum protein globulin
▪Struktur seperti huruf Y
▪Antigen-antigen binding site
▪The term “antibody” refers to its function, which is
to bind to an antigen
 SEL PENGHASIL SISTEM IMUN

TIDAK TERDAPAT BUTIRAN TERDAPAT BUTIRAN

SITOPLASMA SITOPLASMA

Sel B: penghasil antibodi

ANTIBODI ATAU IMUNOGLOBULIN (IG)
 ANTIBODI POLIKLONAL DAN
MONOKLONAL
▪Antibodi poliklonal:
▪Antibodi yang mengenali banyak epitop
dari antigen
▪Kurang spesifik
▪ Antibodi monoklonal:
▪ Antibodi yang hanya mengenali
satu epitop dari antigen
▪ Spesifik
▪ Berasal dari satu (mono) sel hybrid
▪ Klon: sekelompok sel yang berasal
dari satu sel, secara genetik sama
 TEKNOLOGI HIBRIDOMA UNTUK
PRODUKSI MAB
Nobel prize (1984)
1. Imunisasi mencit dengan antigen X, antibodi terhadap For the discovery of the principle for
antigen X dihasilkan oleh sel B production of monoclonal antibodies
2. Isolasi dan seleksi sel B penghasil antibodi tehadap X dari
limfa mencit
3. Penggabungan sel B dengan sel mieloma (sel kanker)
dengan PEG (polietilen glikol) atau elektro fusi
▪Sel B: umurnya pendek-penghasil antibodi spesifik
▪Sel mieloma: imortal-dapat dibiakkan terus menerus
▪PABRIK PRODUKSI ANTIBODI YANG TIDAK ADA HABISNYA
4. Penggabungan antara sel B dengan sel mieloma
menghasilkan sel hibrid (hibridoma)
SELEKSI SEL HIBRIDOMA
▪ Medium HAT (hipoxantine, aminopterin, timidin)
▪ Aminopterin (obat) menghambat sintesis DNA jalur de
novo
▪ sel mensintesis nukleotida melalui jalur salvage
▪ Sel memiliki dua jalur dalam sintesis nukleotida yaitu jalur de
novo dan jalur salvage (non-esensial/penyelamatan)
▪ Sel B
▪ HGPRT positif (HGPRT: hypoxanthine phosphoribosyl
transferase) merupakan enzim untuk sintesis basa
purin/DNA jalur salvage)
▪ HGPRT mengkatalis pembentukan nukleotida purin dari
ribosa, hipoxantin, dan guanin.
▪ Jalur de novo dan salvage on
▪ Sel mieloma
▪ HGPRT negatif: jalur salvage off
▪ Jalur de novo on
Sintesis nukleotida dari Sintesis nukleotida dari
prekursor metaboliknya: daur ulang basa bebas
asam amino, ribosa-5-fosfat, atau nukleosida dari
CO2, dan unit satu karbon pemecahan asam nukleat.
MAB UNTUK TERAPI KANKER
Kanker kelenjar getah bening
Kanker sel darah putih (leukemia)
Kanker payudara
Kanker perut (lambung)
Multipel myeloma
 TRASTUZUMAB (HERCEPTIN): KANKER PAYUDARA

❖Pada sel kanker payudara, terjadi overekspresi HER2

❖Protein ini berperan dalam tranduksi sinyal untuk proliferasi sel
❖Semakin banyak HER2 maka proliferasi sel meningkat
❖mAb menghambat EGF (epidermal growth factor) berikatan dengan reseptor-nya, ekspresi HER2 dihambat
❖Proliferasi sel yang sangat cepat tidak terjadi
MAB UNTUK TES
KEHAMILAN
TERIMA KASIH
THE THREE FUNCTIONS OF ANTIBODIES
1. Antibodies are secreted into the blood and mucosa, where they
bind to and inactivate foreign substances such as pathogens and
toxins (neutralization).
2. Antibodies activate the complement system to destroy bacterial
cells by lysis (punching holes in the cell wall).
3. Antibodies facilitate phagocytosis of foreign substances by
phagocytic cells (opsonization).

https://www.mblbio.com/bio/g/support/method/antibody.html
ANTIBODIES AND THE FOUR KEY FEATURES
OF THE IMMUNE SYSTEM

1. Specificity of antibodies: Antibodies precisely recognize toxins

and pathogens.
2. Diversity of antibodies: Antibodies against a variety of antigens
preexist in the body.
3. Immunological memory: We don’t don’t develop symptoms of
measles
4. Immune tolerance: Self cells and tissues are not normally
attacked.
https://www.mblbio.com/bio/g/support/method/antibody.html
IMMUNE TOLERANCE AND AUTOIMMUNE
DISEASES
“Why don’t tens to hundreds of millions of B cells recognize and attack self-tissues?”
Antibodies recognize all types of antigens, except self-antigens. This feature is called
“immune tolerance.” B cells that react to self-antigens are generated, but are
eliminated within the bone marrow. Even if some autoreactive B cells evade the
elimination process and reach the periphery, those B cells that produce antibodies to
self-antigens (autoantibodies) are inactivated by another mechanism including
regulation by Tregs.
When these mechanisms are disrupted, “autoimmune disease” develops,
characterized by immune cell-mediated self-tissue attack. Possible causes of
autoimmune disease include viral infection, high fever, pregnancy, and the recently
proposed abnormalities in the intestinal microbiome. However, the details of the
mechanism remain unknown.

https://www.mblbio.com/bio/g/support/method/antibody.html
THE SPECIFICITY OF ANTIBODIES

❖Each antibody recognizes one specific antigen.

For example, an antibody that recognizes the mumps virus cannot
recognize the measles virus. Conversely, an antibody that recognizes
the measles virus cannot recognize the mumps virus. This feature is
called “antibody specificity.”
❖Each B cell (antibody-producing cell) produces one kind of antibody.
However, pathogens produce millions of harmful factors.
❖Then, how does the body defend itself against countless harmful
factors?
THE DIVERSITY OF ANTIBODIES AND
IMMUNOLOGICAL MEMORY
Tens to hundreds of millions of different B cells are circulating in the
body so that every antigen is recognized. In other words, the body is
prepared for the invasion of pathogens by possessing B cells that
produce unique antibody molecules. This feature is called “antibody
diversity.”

After an infection, the cells producing pathogen-specific antibodies

multiply and increase proportionally. As a result, the body is protected
from repeated infection. This feature is called “immunological
memory.”
https://www.mblbio.com/bio/g/support/method/antibody.html
GENE REARRANGEMENT
Antibody-producing B cells are produced in the bone marrow and mature in the periphery. During
B-cell maturation, the antibody genes (immunoglobulin genes) undergo recombination, generating
an enormous repertoire of antigen-binding sites (the variable region). This phenomenon is called
“gene rearrangement.”
The gene locus encoding the H chain variable region:
The locus contains an array of about 100-300 V gene segments, about 25 D gene segments, and 6
J gene segments. One each of the V, D, and J gene segments are selected and joined together.

The gene locus encoding the L chain variable region:

There are two loci: κ and λ.
The κ locus consists of an array of about 40 V and 5 J gene segments. The λ locus consists of an
array of about 30 V and 4 J gene segments. One each of the V and J gene segments are selected
and joined together.
Immunoglobulins (antibodies) to countless antigens are produced from a limited number of genes by
recombination of gene segments. Gene rearrangements also occur during T cell maturation in the
thymus.

https://www.mblbio.com/bio/g/support/method/antibody.html