Therapeutic Monoclonal Antibodies: Clinical Applications

Yanjie Sun

1,*,†

, Zhuoyun Wan

2,†

and Zixiao Zhang

3,†

Department of Medicine, HenanVocational College of Nursing, Anyang, 455000, China

Clark University, Worcester, MA01610, U.S.A.

School of Management,

Tianjin University of Technology, Tianjin, 300382, China

Keywords:

Monoclonal Antibodies, Clinical Applications, Cancer Treatment, SARS-Cov-2.

Abstract:

Diagnostic and therapeutic monoclonal antibodies (mAbs) have a broad application prospect, conducive to

mass production by optimizing the quality of monoclonal antibodies and improving productivity. The number

of monoclonal antibodies approved for the treatment and use has increased significantly over the years. Some

improvements and modifications have been made given monoclonal antibody’s side effects and limitations.

These improvements facilitate monoclonal antibodies in various therapeutic applications, from treating

noncontagious diseases such as cancer, like breast cancer, to using monoclonal antibodies to cure infectious

diseases caused by viruses, such as viruses Covid-19 and its causing agent SARS-CoV-2. This paper reviews

monoclonal antibody’s clinical application, focusing on these two main categories and discussing its potential

future development trend.

1 INTRODUCTION

Monoclonal antibodies are homologous antibodies

produced by single clone hybridoma cells that only

recognize a specific epitope. Monoclonal antibodies

have the properties of general antibodies; monoclonal

antibodies are a type of globulin produced by the

proliferation and differentiation of B cells into plasma

cells. Such as pathogens) specifically bind, and exert

an immune effect under the participation of other

immune molecules and cells. In addition to the

general properties of antibodies, monoclonal

antibodies also have their particularities. Monoclonal

antibodies have mouse immune spleen cells (B cells)

and immortal myeloma cells fused together to form a

hybridoma cell. This hybridoma cell not only has the

ability to reproduce indefinitely but also has the

ability to secrete antibodies. Therefore, after in vitro

culture, antibodies can be secreted indefinitely.

Clinically, such as the application of diphtheria

exotoxin monoclonal antibody to treat

Corynebacterium diphtheriae; the application of anti-

endotoxin lipid A monoclonal antibody to treat

G~bacterial sepsis, etc., using a monoclonal antibody

as an affinity column can separate and purify the

†

These authors contributed equally

content of extremely low solubility Antigens such as

hormones, cytokines, and tumor antigens that are

difficult to purify; open up a new way for substance

purification; prepared monoclonal antibodies to

recognize specific receptors on the cell surface, and

couple anti-tumor drugs (such as toxins or radioactive

substances). Connect to it to build biological missiles

to overcome human diseases-tumors.

Monoclonal antibodies are vital in tumor

diagnosis and treatment. It is of great significance to

use new secretory antigens that can promote tumor

growth or metastasis as antibody blocking targets

(Scott, 2012). Monoclonal antibody-targeted therapy

for tumors is: monoclonal antibodies against tumor

antigens are attached to chemotherapy or

radiotherapy agents, and use the targeting effect of the

monoclonal antibody to carry the drug or

radiotherapy substance to the target organ and

directly kill the target cell. In addition, radio

immunoimaging can be realized to aid tumor

diagnosis by linking the radio markers with

monoclonal antibodies and applying them to patients.

Although monoclonal antibodies against tumor-

specific antigens remain to be studied, monoclonal

antibodies against tumor-associated antigens such as

alpha-fetoprotein, tumor basic protein and

Sun, Y., Wan, Z. and Zhang, Z.

Therapeutic Monoclonal Antibodies: Clinical Applications.

DOI: 10.5220/0012020800003633

In Proceedings of the 4th International Conference on Biotechnology and Biomedicine (ICBB 2022), pages 335-342

ISBN: 978-989-758-637-8

 2023 by SCITEPRESS – Science and Technology Publications, Lda. Under CC license (CC BY-NC-ND 4.0)

335

carcinoembryonic antigen have been used in clinical

trials for a long time. With the application of

lymphocytic hybridoma technology, many

hybridoma cell lines resistant to human tumor

markers have been established. Radionuclide-labeled

monoclonal antibodies can be used for in vivo

diagnosis, and combined with X-ray tomography

technology, it can make a quantitative diagnosis of

the size of the tumor and its metastasis. At present,

monoclonal antibodies have their limitations in the

diagnosis and treatment of tumors. Monoclonal

antibodies are mainly murine-derived antibodies,

which are satisfactory as in vitro diagnostic reagents

(Abès, 2011). If murine-derived monoclonal

antibodies are used in humans as biological

preparations, the heterogeneous proteins in the serum

of heterogeneous animals can cause allergic reactions

and even life-threatening (Marabelle, 2015). Human

monoclonal antibodies or humanized antibodies are

important for disease treatment. Although there are

reports that the culture of these cell lines is very

unstable, the human chromosomes in the fusion cells

are often selectively lost, making cell lines difficult to

cultivate. Maintain cultivation. Therefore, the

preparation of human monoclonal antibodies is a

problem that needs to be solved urgently, but no

significant progress has been made in this regard.

Prospects Various preparation technologies of

monoclonal antibodies are changing with each

passing day, but they still have their own advantages

and disadvantages and require resource integration

(Jahanshahlu, 2020). The library of antibody library

technology can be derived from immunized wild-type

or transgenic animals, or it can be derived from a

single B cell sorted out from a patient who has

recovered from a specific disease. In short, several

preparation techniques can be used interchangeably

(Cruz-Teran, 2021).

This article mainly describes the progress and

problems of monoclonal antibodies in tumor

diagnosis and treatment and new coronavirus vaccine

research. With the continuous progress and

development of research technology, monoclonal

antibody is expected to achieve a breakthrough in

tumor diagnosis and treatment, and will also be better

applied to the development of vaccines against new

coronaviruses (Anti-SARS-CoV-2 neutralizing

monoclonal antibodies: clinical pipeline – PubMed,

2021).

2 CLINICAL APPLICATIONS: IN

CANCER TREATMENT

Antibody-based cancer treatment has grown well-

established over the last 20 years, and it is currently

one of the most effective and critical techniques for

treating people with solid tumors and blood cancers

(Bayer, 2019).

2.1 For Oncology Indications, Around

30 mAbs Have Been Received

A wide variety of new therapeutic antibodies are

being evaluated in early and late-stage clinical

studies. When compared to traditional

chemotherapeutic drugs, most antibodies that have

been authorized have different, and frequently lesser

side effects.

Chemo therapies based on monoclonal antibodies

(mAbs) began to appear.

By selectively binding an antigen on a malignant

cell, mAbs might decrease non-specific toxic effects,

identify malignant cells, and either change cellular

signaling pathways toward a therapeutic outcome or

activate an immune system response against with the

cancer cell.

Antibody-drug conjugates (ADCs) are an immune

conjugation made up of a cytotoxic medication (the

payload) linked to a monoclonal antibody via a

biochemical linker. The ADC is intended to

specifically convey the ultra-toxic load direct to the

tumor cells or tissues (Chau, 2019).

Five ADCs have been approved for use in the

market, while more than 100 are being studied at

various levels of clinical testing.

The ADC is now being used in breast cancer

therapy in a variety of forward ways. This Review

will use triple-negative breast cancer (TNBC) as an

example to present the properties of mAbs therapy.

TNBC lacks the expression of progesterone receptor,

estrogen receptor (ER) and human epidermal growth

factor receptor 2 (HER2), and belongs to the invasive

breast cancer subtype. Traditional and growth factor

receptor or endocrine targeted therapies do not work

for women with TNBC. The predominant therapeutic

technique for patients is a mix of radiotherapy,

surgical intervention, and systemic chemo.

These therapeutic methods provide little clinical

benefit, and varieties of side effects such as

neutropenia and cardiotoxicity are common. Even

with therapy, initial TNBC cancers often distant

organ metastasis such as the the brain and lungs,

causing the low overall survival seen in TNBC

ICBB 2022 - International Conference on Biotechnology and Biomedicine

336

patients. Small molecule antagonists targeting DNA

double strand damage repair pathways in TNBC have

demonstrated to be a potential option for enhancing

TNBC survival rates. The FDA has authorized two

poly ADP-ribose polymerase (PARP) antagonists,

talazoparib and olaparib, for the therapy of HER2

negative later-stage cancer cases containing germ line

changes in the breast tumor vulnerability gene 1/2

(BRCA1/2).

The progression-free survival (PFS) was 7 months

for TNBC patients undergoing olaparib, compared to

4.2 months for patients who received single-agent

chemo (ClinicalTrials.gov Identifier NCT02000622).

In compared to chemotherapy- treated clients, PFS

for TNBC patients undergoing talazoparib was

prolonged by around 90 days (ClinicalTrials.gov

Identifier NCT01945775).

Though PARP inhibitors exhibited therapeutic

effectiveness as targeted therapies for TNBC, client

survival improved only marginally. Taken all

together, Additional treatments are desperately

required, which suited to the therapy of TNBC, to

stop the invasive disease's fast clinical progression.

Current cancer immunotherapy research on the

field of meeting the unmet clinical need in TNBC

presents a significant possibility. In the realm of

TNBC, programmed death-ligand 1 (PD-L1) is a

famous regulatory molecule that has recently

attracted consideration as a prospective immuno-

biological cancer therapy target.

The atezolizumab with the chemotherapeutic drug

nab-paclitaxel, an anti-PD-L1 monoclonal antibody,

the FDA authorized the conjunction for the therapy of

locally advanced, PD-L1positive unresectable, or

metastatic TNBC. The TNBC patient，whose median

overall survival for PD-L1 positive was

approximately 10 months longer than for those taking

a placebo plus nab-paclitaxel ， received

atezolizumab with nab-paclitaxel.

After that, sacituzumab govitecan, the first ADC

(antibody–drug conjugate), was approved for the

therapy of metastatic TNBC. These ground-breaking

approvals have paved the way for a new era of

immunotherapy in TNBC (Dees, 2021). 86%

Bispecific antibody treatment strategies in the clinical

pipeline, which are authorized for oncology

treatment, reached. The progress of DNA

recombinant technology has led in the manufacturing

of a plethora of cancer-targeting bispecific antibodies

in a variety of configurations.

A bispecific antibody, conventional bivalent IgG-

like, produced employing knobs into holes

technology, has a fragment crystallizable region (Fc

region) which is suitable of regulating regulatory

activities, as well as fragment antigen-binding (Fab)

regions which can detect and recognize multiple

antigens. Even though some bispecific antibody

models include a muted Fc region, there are certain

bispecific antibody forms that do not have an Fc

region at all.

Diabody, dual-affinity retargeting (DART),

bispecific killer cell engager, and bispecific T cell

engager (BiTE) are examples of Fab-based bispecific

antibody constructions. The predominantly sum of

bispecific antibodies in medical studies for cancer

therapy have a process of the dual interaction of

cancer cells and immune cells, and are usually

structured as BiTEs. The blinatumomab, for

bispecific antibody development has created a

medical precedent in cancer treatment, which is a

treatment of B cell tumors situated the first-in-class

BiTE.

2.2 Therapeutic Monoclonal

Antibodies (mAbs) Targeting the

ERBB Family of Proteins Have

Shown to Be Effective in Patients

with Solid Tumors

There are many types of tumor-associated antigens

that therapeutic mAbs detect. CD30, CD20, CD52,

and CD33 are hematopoietic differentiation antigens,

which are glycoproteins that are normally linked with

a CD grouping. Both malignant cells and Normal

include cell surface differentiation antigens, which

are a broad array of carbohydrates and glycoproteins.

Growth factors receptors and growth factor are often

antigens engaged in differentiation signaling and

growth.

United therapy with immune checkpoint

suppressant, and a mass of TNBC targets such as

Ephrin receptor A10 (EphA10), Trophoblast Cell-

Surface Antigen 2 (Trop2), carcinoembryonic-

antigen-related cell-adhesion molecule 5 (CEACAM

5), Epithelial cell adhesion molecule (EpCAM), P-

cadherin, mesothelin, and EGFR have all been

integrated into immune cell-redirecting bispecific

antibody constructions. Furthermore, several

receptors on TNBC cells, such as EGFR, Notch and

HER3, can be recognized by bi-specific antibodies.

Bispecific antibodies have been developed as

potential therapies for malignant tumors by

transferring the cytotoxic effects and load of the

immune system to cancer cells, or by simultaneously

activating two functional receptors of a tumor cell. A

fab - like bispecific antibody was found to participate

in CD16 (FcRIII). A typical antibody-dependent

cytotoxicity (ADCC) mechanism is triggered when a

Therapeutic Monoclonal Antibodies: Clinical Applications

337

stimulating receptor CD16, widely observed on NK

cells, connects to the Fc region of an antibody

conjugated to a target antigen.

Human epidermal growth factor receptor 3

(HER3), extracellular signal - regulated tyrosine

kinase, and also another a bispecific diabody-Fc

integration protein marking EGFR found on TNBC

cells, was recently developed. The assay methods of

cell culture in vitro monolayer and more complicated,

physiologically associated 3D perfect sphere models

proved that the EGFR ×HER3 bispecific antibody

effectively inhibited TNBC cellular proliferation.

Furthermore, in an murine models with orthotic

MDA-MB-468 TNBC, the EGFR× HER3 bispecific

suppressed growth and the survival of TNBC cancer

stem cells (CSCs).

Positively, HER3 and Multi-specific EGFR

identification has shown clinical effectiveness and

safety in other cancers like as colorectal cancer and

head and neck cancer identifier. In some other

research, dual HER3 and EGFR blockade has been

seen to increase TNBC cell sensitivity to

phosphatidylinositol 3-kinase (PI3K) inhibitors,

revealing the need for more research into combination

treatment for TNBC.

Interestingly, EGFR Notch bispecific antibodies

augmented the response to therapy of TNBC cells to

PI3K inhibition, as demonstrated by a significant

decrease in TNBC CSC communities. The same

phenomenon was found with EGFR × Notch

bispecific antibodies.

Recently, an innovative technique for delivering

immune response therapeutic approaches to TNBC

cancers using lipid-coated phosphate and calcium

nanoparticles was established (LCP NPs). The LCP

NPs were not only designed and synthesized on the

outside with a PEG × EGFR bispecific antibody but

was also added with cell apoptosis siRNA and

indocyanine green on the inside of nanoparticle.

Consequently, LCP NPs chemically modified

with PEG × EGFR bispecific antibodies function in

TNBC cancer cells with EGFR-expressing, when

exposed to near-infrared radioactivity in vitro, and

removed TNBC tumors completely and induced cell

death in TNBC cells in vivo. One study shows that

bispecific antibodies can be used in photothermal

therapy/a gene therapy-based nanoparticle platform

to cure TNBC tumors.

Table 1: Tumor-associated antigens targeted by therapeutic monoclonal antibodies.

Antigen

cate

Examples of

anti

ens

Examples of therapeutic mAbs

raised a

ainst these tar

ets

Tumor types expressing antigen

Haematopoietic

differentiation

antigens

CD20

Rituximab Non-Hod

kin’s l

homa

Ibritumomab tiuxetan and

tositumomab

Lymphoma

CD30 Brentuximab vedotin Hod

kin’s l

homa

CD33 Gemtuzumab ozogamicin Acute myelogenous leukemia

CD52 Alemtuzumab Chronic l

hoc

tic leukemia

Glycoproteins

expressed by

solid

tumors

EpCAM IGN101 an

adecatumumab Epithelial tumors (breast, colon an

lung)

CEA Labetuzumab Breast, colon an

lun

tumors

gpA33 huA33 Colorectal carcinoma

Mucins Pemtumomab an

ore

ovomab Breast, colon, lun

ovarian tumors

TAG-72 CC49 (minretumomab) Breast, colon an

lung tumors

CAIX cG250 Renal cell carcinoma

PSMA J591 Prostate carcinoma

Folate-binding

protein

MOv18 and MORAb-003

(farletuzumab)

Ovarian tumors

Glycolipids

Gangliosides

(such as GD2,

GD3 and

GM2

)

3F8, ch14.18 and KW-2871

Neuroectodermal tumors and some

epithelial tumors

Carbohydrates Le

hu3S193 an

IgN311 Breast, colon, lung an

rostate tumors

Targets of anti-

angiogenic

mAbs

VEGF Bevacizumab Tumo

vasculature

VEGFR IM-2C6 an

CDP791 Epithelium-derive

soli

tumors

Integrin αVβ3

Etaracizumab Tumor vasculature

Integrin

αVβ31

Volociximab Tumor vasculature

Growth and

differentiation

EGFR

Cetuximab, panitumumab,

nimotuzumab an

806

Glioma, lung, breast, colon, and head and

nec

tumors

ICBB 2022 - International Conference on Biotechnology and Biomedicine

338

signaling

ERBB2 Trastuzumab and pertuzumab

Breast, colon, lung, ovarian and prostate

tumors

ERBB3 MM-121

Breast, colon, lung, ovarian and prostate,

tumors

MET

AMG 102, METMAB and SCH

900105

Breast, ovary and lung tumors

IGF1R

AVE1642, IMC-A12, MK-0646,

R1507

CP 751871

Glioma, lung, breast, head and neck, prostate

and

thyroi

cance

EPHA3

KB004 and IIIA4

Lung, kidney and colon tumors, melanoma,

glioma

haematolo

ical mali

nancies

TRAILR1 Mapatumumab (HGS-ETR1)

Colon, lung and pancreas tumors and

haematolo

ical mali

nancies

TRAILR2 HGS-ETR2 and CS-1008

RANKL Denosumab Prostate cance

one metastases

Stromal and

extracellular

matrix

anti

ens

FAP Sibrotuzumab and F19

Colon, breast, lung, pancreas, and head and

neck

tumours

Tenascin 81C6 Glioma,

reast an

rostate tumors

CAIX, carbonic anhydrase IX; CEA, carcinoembryonic antigen; EGFR, epidermal growth factor receptor; EpCAM,

epithelial cell adhesion molecule; EPHA3, ephrin Receptor A3; FAP, fibroblast activation protein; gpA33, glycoprotein

A33; IGF1R, insulin-like growth factor 1 receptor; Le

, Lewis Y antigen; mAbs, monoclonal antibodies; PSMA,

prostate-specific membrane antigen; RANKL, receptor activator of nuclear factor-kB ligand; TAG-72, tumor-associated

glycoprotein 72; TRAILR, tumor necrosis factor-related apoptosis-inducing ligand receptor; VEGF, vascular endothelial

rowth factor; VEGFR, VEGF rece

tor.

3 CLINICAL APPLICATIONS: IN

INFECTIOUS DISEASES

As of recent years, at least 20 neutralizing

monoclonal antibodies (mAbs) medicines are now in

late-stage clinical studies or have been permitted for

use in treating a variety of transmittable diseases,

including influenza viruses, Ebola, respiratory

syncytial viruses (RSV), and others (Wrapp, 2020).

Targeting SARS-CoV-2 as the causative agent of

COVID-19 has been a hot research topic since the

pandemic. Monoclonal antibodies against SARS-

CoV-2 have the potential to be employed for both

infection prevention and treatment. SARS-CoV and

MERS-CoV monoclonal antibodies have already

been shown to be beneficial in animal models

(Taylor, 2021).

There were no approved COVID-19 preventative

vaccinations or therapies when the outbreak began.

Blocking mAbs are among the finest candidates for

neutralizing viral infection due to their exceptional

antigen specificity. The researchers aimed to locate

and manufacture blocking monoclonal antibodies

from memory B-cell libraries of newly cured

individuals to counteract the virus from entering

healthy host cells. Similar to SARS-CoV, which

caused an outbreak of SARS in 2002-2004, SARS-

CoV-2 also uses a high-glucose homologous trimer

spike (S) protein to bind to receptors and virus entry

(Zhou, 2020). Two subunits, S1 and S2, constitute the

S protein of SARS-CoV-2 and undergo drastic

conformational changes that expose the critical

residues of the receptor-binding domain (RBD)

binding to the receptor, thereby enabling the binding

of the host cell receptor human angiotensin-

converting enzyme 2 (hACE2), which SARS-CoV

and SARS-CoV-2 share. S protein is metastable, and

RBD binding to the hACE2 receptor may promote

S2-mediated viral host membrane blending and viral

entrance, as S1 protein is detached from S2 protein.

RBD is an exposed mark for neutralizing antibodies

because it is involved in SARS-CoV-2 access into

healthy host cells. An S1-targeting monoclonal

antibody made from genetically modified mice

immunized with the expression of human Ig

differential chains has recently been shown to

counterbalance SARS-CoV-2 and SARS-CoV

contagion; it is, however, neutral of the RBD-HACE2

connection being blocked due to unknown reasons

(Cohen, 2021).

The researchers primarily looked for antibodies to

SARS-CoV-2 S1 protein IgG in blood serum from

individuals who had lately survived from COVID-19.

Using an enzyme-linked immunosorbent assay

(ELISA), they discovered that the majority of the 26

recovered COVID-19 patients were capable of

Therapeutic Monoclonal Antibodies: Clinical Applications

339

producing a high quantity of SARS-CoV-2 S1-

specific IgG antibodies. Relatively low anti-S1 IgG

antibody responses were only found in 3 patients.

They also discovered that SARS-CoV-2 IgG

antibodies explicit to RBD were detected in all of the

affected individuals. Researchers successfully

manufactured two human neutralizing monoclonal

antibodies utilizing SARS-CoV-2 RBD-specific

memory B cells obtained from patients who

recovered from the disease. These two monoclonal

antibodies attach to SARS-CoV-2 RBD and disrupt

the connection between SARS-CoV-2 RBD and the

hACE2 receptor, thereby neutralizing SARS-CoV-2

S protein pseudovirus contamination (Chen, 2020).

Passive vaccination uses antigen-specific

monoclonal or polyclonal antibodies derived from

animal or human blood sources. Two significant

uncertainties in passive immunization may also exist

in neutralizing monoclonal antibodies: first, whether

they could potentially affect long-term physical

immunity as prevention or treatment. It is unclear if

the existence of circulating neutralizing monoclonal

antibodies affects protective immunity via infection

memory or vaccination, given the high doses used and

antibody half-lives. Rodent and primate models of

RSV infection suggest that passive antibody transfer

does reduce the development of the recipient’s human

immunity. Nevertheless, long-term memory is still

adequate to defend the host from second-time

reinfection, thanks to the presence of an undamaged

T-cell memory chamber (Marovich, 2020). Second,

will the mutation of resistant virus affect the

therapeutic effectiveness? Clinical evidence suggests

that SARS-CoV-2 spikes (S) protein mutations can

evade polyclonal serum, resulting in lower

convalescent plasma neutralization activity against

particular viral variants. As a result, monoclonal

antibodies may require a mixture therapy of

monoclonal antibodies to boost clinical efficacy and

prevent treatment failure in the future, depending on

the source of infection and the targeted epitope

(Crowe, 2001).

It is essential to notice that Taylor also proposed

that “due to the vast number of persons sick and the

high intensity of virus transmission among humans,

the COVID-19 pandemic poses a bigger risk of

escape mutations than the Ebola outbreak did”, which

was later approved by the case of Delta variant and

Omicron variant.

Figure 1: Neutralizing mAbs inhibit SARS-CoV-2 by binding to the spike (S) protein.

RT-PCR as a proxy for viral infection or viral

replication scale for SARS-CoV-2. According to the

findings, the monoclonal antibody serves as an

antiviral agent, reducing viral load in the

nasopharynx. The effect of monoclonal antibodies

and other medications on viral load could be a crucial

criterion for designing therapies to treat early

COVID-19 infections (Crowe, 2001).

An effective vaccine is necessary to cure the

epidemic. The functional and active evaluation of

several COVID-19 vaccine candidates is expected to

shorten the vaccine development process from years

ICBB 2022 - International Conference on Biotechnology and Biomedicine

340

or even decades to 12 to 18 months. Monoclonal

antibodies offer another way to prevent COVID-19.

Passive monoclonal antibody infusion as a

prophylactic treatment before or after exposure

provides immediate protection from an infection that

can last weeks or even months. To extend the possible

protection, the new technique that can modify the

antibody Fc region to extend the half-life of the

monoclonal antibody by up to several months,

depending on the concentration of the desired

monoclonal antibody. Even after an uninfected

person has been vaccinated, the benefits of passive

immunization can be seen during the period it will

take for the immune system to establish an immune

response using the mRNA information carried by the

vaccine. Neutralizing monoclonal antibodies is

especially helpful in health care facilities, homes, and

kindergartens where people with low immunity

gather because outbreaks are common and

devastating. During epidemics, nursing home patients

are given monoclonal antibodies. They may help slow

the disease’s course during early infections that go

untreated. Furthermore, the elderly and those with

underlying problems may not have a sturdy protective

response to vaccination, necessitating the use of

monoclonal antibodies to give protection (Taylor,

2021).

4 CONCLUSION

The attention of therapeutic monoclonal antibodies is

increasing year by year. Their high specificity for

antigen can offer various applicable medical

treatments, and the emergence of molecularly

targeted drugs has made the growth of a new

generation of therapeutic medications possible. In this

review paper, human monoclonal antibodies are

introduced as homologous antibodies produced by

single clone hybridoma cells, produced by the

proliferation and differentiation of B cells. The

clinical application of mAb therapies can be separated

into two main categories, cancer treatment, and

infectious diseases medicine. The most successful

class of antibodies targeting the ERBB family is the

usage of therapeutic mAbs on patients with solid

tumors, and one of the examples in breast cancer.

Focusing on treating infectious diseases, the efficacy

of mAb therapies targeting SARS-CoV-2 was

discussed as the causative agent of Covid-19 and its

advantage compared to CPT. In future studies of mAb

therapies targeting SARS-CoV-2, several

combination therapies are under clinical trials, like

bamlanivimab and etesevimab, which are expected to

overcome or prevent antibody resistance.

REFERENCES

Abès R, Teillaud JL. Modulation of tumor immunity by

therapeutic monoclonal antibodies. Cancer Metastasis

Rev. 2011;30(1):111-124.

Anti-SARS-CoV-2 neutralizing monoclonal antibodies:

clinical pipeline - PubMed. Accessed December 29,

2021.

Bayer V. An Overview of Monoclonal Antibodies. Semin

Oncol Nurs. 2019;35(5):150927.

Cruz-Teran C, Tiruthani K, McSweeney M, Ma A, Pickles

R, Lai SK. Challenges and opportunities for antiviral

monoclonal antibodies as COVID-19 therapy. Adv

Drug Deliv Rev. 2021;169:100-117.

Chau, C. H., Steeg, P. S., & Figg, W. D. (2019). Antibody–

drug conjugates for cancer. The Lancet, 394(10200),

793–804.

Chen, X., Li, R., Pan, Z., Qian, C., Yang, Y., You, R., Zhao,

J., Liu, P., Gao, L., Li, Z., Huang, Q., Xu, L., Tang, J.,

Tian, Q., Yao, W., Hu, L., Yan, X., Zhou, X., Wu,

Y., … Ye, L. (2020). Human monoclonal antibodies

block the binding of SARS-CoV-2 spike protein to

angiotensin converting enzyme 2 receptor. Cellular &

Molecular Immunology, 17(6), 647–649

Cohen, M. S. (2021). Monoclonal Antibodies to Disrupt

Progression of Early Covid-19 Infection. The New

England Journal of Medicine, 384(3), 289–291

Crowe, J. E., Firestone, C. Y., & Murphy, B. R. (2001).

Passively acquired antibodies suppress humoral but not

cell-mediated immunity in mice immunized with live

attenuated respiratory syncytial virus vaccines. Journal

of Immunology (Baltimore, Md.: 1950), 167(7), 3910–

3918

Dees, S., Ganesan, R., Singh, S., & Grewal, I. S. (2021).

Bispecific Antibodies for Triple Negative Breast

Cancer. Trends in Cancer, 7(2), 162–173.

Jahanshahlu L, Rezaei N. Monoclonal antibody as a

potential anti-COVID-19. Biomed Pharmacother

Biomedecine Pharmacother. 2020;129:110337.

Marabelle A, Gray J. Tumor-targeted and immune-targeted

monoclonal antibodies: Going from passive to active

immunotherapy. Pediatr Blood Cancer.

2015;62(8):1317-1325.

Marovich, M., Mascola, J. R., & Cohen, M. S. (2020).

Monoclonal Antibodies for Prevention and Treatment

of COVID-19. JAMA, 324(2), 131–132

Scott AM, Wolchok JD, Old LJ. Antibody therapy of

cancer. Nat Rev Cancer. 2012;12(4):278-287.

Taylor, P. C., Adams, A. C., Hufford, M. M., de la Torre,

I., Winthrop, K., & Gottlieb, R. L. (2021). Neutralizing

monoclonal antibodies for treatment of COVID-19.

Nature Reviews Immunology, 21(6), 382–393

Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A.,

Hsieh, C.-L., Abiona, O., Graham, B. S., & McLellan,

Therapeutic Monoclonal Antibodies: Clinical Applications

341

J. S. (2020). Cryo-EM structure of the 2019-nCoV

spike in the prefusion conformation. Science

Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L.,

Zhang, W., Si, H.-R., Zhu, Y., Li, B., Huang, C.-L.,

Chen, H.-D., Chen, J., Luo, Y., Guo, H., Jiang, R.-D.,

Liu, M.-Q., Chen, Y., Shen, X.-R., Wang, X., … Shi,

Z.-L. (2020). A pneumonia outbreak associated with a

new coronavirus of probable bat origin. Nature,

579(7798), 270–273

ICBB 2022 - International Conference on Biotechnology and Biomedicine

342