NKG2A: A Novel Immune Checkpoint Protein for Cancer Treatment

Qiwen Huang

Ulink College Guangzhou, Guangzhou, Guangdong, China

Keywords:

Cancer Immunotherapy, Immune Checkpoint Inhibitor (ICI), Monoclonal Bodies (mAbs), CD94/NKG2A,

Monalizumab.

Abstract:

Immune checkpoint inhibitor (ICI) drugs have been figured prominently in various of cancer immunotherapy.

Immune checkpoint inhibitor monoclonal antibodies (mAbs) targeting cytotoxic T-lymphocyte antigen 4

(CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1), have achieved unprecedented

improvements. Nonetheless, due to some issues such as tumor resistance, genetic heterogeneity, and its

intricacy of immune regulatory pathways, immunotherapy remains a major challenge. As a result, it's critical

to discover further about immunological checkpoints and the application of their inhibitors in clinical practice.

The potential inhibitory CD94/NKG2A receptor has been explored in recently, which involve in the

stimulation of both natural killer (NK) and CD8+ T cell immunological activity, as well as predominantly

link to immune cell-tumor interaction. However, the specific mechanisms for immune regulation, NKG2A-

targetd inhibitors and related clinical trials are still underestimated. Therefore, we'll look at the basic structure

and function of CD94/NKG2A, and its immune regulatory mechanisms, as well as the current NKG2A-

targeted clinical results in the review.

1 INTRODUCTION

Immune checkpoint protein originally acts as

mediators for protection of normal tissues from

carcinogenesis. However, it is found that tumor cells

utilize some of the immune checkpoints as a

significant channel for evasion of immune

surveillance and immune resistance. To date, immune

checkpoint inhibitor (ICI) drugs that efficiently block

or modulate the ligand-receptor interaction have been

developed to improve the treatment for cancers. The

ICI targeting PD-1/PD-L1 and CTLA-4 were showed

therapeutically potent and improved the clinical

benefits for patients. Seven of them therefore were

approved by the US Food and Drug Administration

(FDA), involving one for CTLA-4 (ipilimumab), three

for PD-1 (nivolumab, pembrolizumab, cemiplimab)

and another three for PD-L1 (atezolizumab,

avelumab, duralumab) (Verma, Sprave, Haque, et al.

2018). Although ICIs displayed remarkable outcomes

in clinical trials for cancers, e,g non-small cell lung

carcinoma (NSCLC), melanoma, and relapsed or

refractory Hodgkin’s lymphoma, it can only benefit a

small number of patients due to the complicate

mechanisms of different types of tumor micro-

environment (TME) for protection of tumor against

immune responses (Darvin, Toor, Sasidharan Nair,

Elkord, 2018). What’s worse, some of the patients

who are treated with immune checkpoints inhibitors

risk serious immune-related adverse events (irAEs),

and hyper-progression (Feng, Roy, Masson, Chen,

Humphrey, Weber, 2013). Therefore, more effective

and safe molecular targets and drugs are essential for

improvement of ICI discovery and treatments.

NKG2A, an inhibitory receptor that regulates both

innate and adaptive immunity through subsets of T

cells and NK cells, that injects new blood into cancer

immunotherapy. NKG2A often expresses on the

membranes of NK cells and T cell subsets as a

heterodimeric proteins by linking with invariant CD94

polypeptide disulfide (Boyington, Riaz, Patamawenu,

Coligan, Brooks, Sun, 1999). NK cells and T cells

have significant effect on limiting both tumor

progression and metastasis (Zaghi, Calvi, Marcenaro,

Mavilio, Di Vito, 2019). The recognition of human

histocompatibility leukocyte Ag-E (HLA-E) on tumor

cells by CD94/NKG2A complex inhibits certain

functions of NK cells and particular types of T cells,

thus speeding up tumor escape from the immune

system5.In this case, tumor immunity can be greatly

enhanced by the inhibition of CD94/NKG2A or the

ligands, although there are limited approved

medicines, established researches and trials about this

1076

Huang, Q.

NKG2A: A Novel Immune Checkpoint Protein for Cancer Treatment.

DOI: 10.5220/0011377500003443

In Proceedings of the 4th International Conference on Biomedical Engineering and Bioinformatics (ICBEB 2022), pages 1076-1083

ISBN: 978-989-758-595-1

receptor. Here, we review the foundational structure

of NKG2A, involving it genetic information, protein

domain and regulatory mechanisms, as well as its

advances and updates in pan-cancers.

2 NKG2A/CD94

2.1 The Structure of NKG2A

NKG2A is an inhibitory member of the NKG2 family

of receptors6, consisting of 233 amino acid. NKG2 is

a C-type lectin-like receptor family including seven

subunit proteins, NKG2A, B, C, D, E, F, and H

(Sullivan, Clements, Beddoe, et al, 2007). Previous

results have demonstrated that NKG2A shows great

similarity in genomic organization and sequence with

NKG2-C, -E and -F, having the same transcriptional

orientation as theirs (Borrego, Kabat, Kim, et al.

2002). However, NKG2A transcript involves an

unique extra 5 untranslated exon (Plougastel,

Trowsdale, 1998). Its C-type lectin domain is

possessed by a type II integral membrane protein

(Glienke, Sobanov, Brostjan, et al, 1998). The

NKG2A molecule carries two immunoreceptor

tyrosine-based inhibitory motifs (ITIMS) in the

intracytoplasmic tail nearly identical to those of the

inhibitory KIRs (Borrego, Kabat, Kim, et al. 2002)

and forms lengthened disulfide-linked heterodimers

with the invariant CD94 protein (Walter, Petersen,

2017). Recent researches have also shown that

NKG2A is expressed in combination with other

proteins in some NK cells (Figure 1A) and T cell

subsets (Figure 1B). The NKG2A receptor has been

found on nearly half of the peripheral NK cells which

are predominantly presented in the CD56high fraction

that contains the more immature cells (Borst L, Burg

SH van der, Hall T van. 2020). Moreover, intra-

tumoral NK cells express rather high frequencies of

NKG2A (van Montfoort, Borst, Korrer, et al, 2018).

The expression of NKG2A In CD8 T cells has been

strictly regulated since peripheral cells hardly display

this receptor, while the majority of intra-tumoral T

cells, particularly those in the tumor

microenvironment, exhibit NKG2A (van Montfoort,

Borst, Korrer, et al, 2018, Hamid, Wang, Yao, et al,

2019).

Figure 1. The expression and interaction of NKG2A in NK

cell (A) and Tcell (B).

The NKG2A ectodomain, with the overall

dimensions 54*33*29 A, is consist of two

perpendicular beta sheets formed by 8 Beta strands,

plus 2 alpha helices (residues 140–149 and 160–169)

on the opposite face of the promotor (Sullivan,

Clements, Beddoe, et al, 2007). The three bonds

stabilizing the NKG2A fold are Cys119-Cys130 for

the connection between the beta2 strand and the N-

terminal loop; Cys147-Cys229 for the connection

between beta7 strand and alpha1 helix; and Cys208-

Cys221 for the connection between beta5 strand to

loop 6 (Sullivan, Clements, Beddoe, et al, 2007).

Therefore, NKG2A is in the same structural

homologous series with CD94 (Sullivan, Clements,

Beddoe, et al, 2007).

The CD94 molecule, a subunit of CD94/NKG2A

receptor with general dimension of 42*37*33 A in

approximation, is made up of an antiparallel beta sheet

with strands 1, 2, 7, an antiparallel beta sheet with

strands 4, 3, 5, and 6, and an alpha helix after strand 2

(Boyington, Riaz, Patamawenu, Coligan, Brooks,

Sun, 1999). It has four intrachain disulfide linkages,

including three invariant disulfides (Cys61–Cys72,

Cys89–Cys174, and Cys152–Cys166) which

presented in long-form C-type lectin (Day, 1994).

Cys59-Cys70 which is the fourth disulfide, links with

N-terminal beta strands and is found uniquely in the

molecular structure of CD94 (Boyington, Riaz,

Patamawenu, Coligan, Brooks, Sun, 1999). Cys58,

the lone interstitial cysteine not found in interchain

disulfide pairing, is supposed to combine with the

NKG2A: A Novel Immune Checkpoint Protein for Cancer Treatment

1077

Cys116 in NKG2A, resulting in the interchain

disulfide in the CD94/NKG2A heterodimer

(Boyington, Riaz, Patamawenu, Coligan, Brooks,

Sun, 1999).

The CD94/NKG2A dimer has the dimension

75*42*38 A with a large dimer interface containing

roughly 1500 A2 of buried surface area (BSA)

(Sullivan, Clements, Beddoe, et al, 2007), at which

CD94 and NKG2A contribute 69% and 31%

respectively (Petrie, Clements, Lin, et al, 2008). The

interaction between the alpha2 helix of NKG2A and

the complementary prolonged loop region of CD94

greatly leads to the asymmetry at the CD94/NKG2A

interface (Sullivan, Clements, Beddoe, et al, 2007).

Additionally, there are two of the amino acids in

CD94/NKG2A locating on the presumed HLA-E

binding site, position 197 in loop 5 (Glu) and position

225 within loop 7 (Ile) (Sullivan, Clements, Beddoe,

et al, 2007).

According to recent researches, tumor infiltration

NK cells and CD8+ T cells express an abnormal

amount of NKG2A which contributes to the poor

cancer prognosis (Zaghi, Calvi, Marcenaro, Mavilio,

Di Vito, 2019). By analyzing the tissue-infiltrating

leukocyte (ITL) from normal livers, intratumor tissues

(IT), peritumor tissues (PT) and intratumor tissues

(IT), Cheng Sun et al had found that the expression of

NKG2A in NK cells from IT was dramatically

increased in comparison with those cells in healthy

livers and PT which also relates to NK cell exhaustion

and to great extent, results in a shorter overall survival

(OS) of patients with hepatocellular carcinoma (Sun,

Xu, Huang, et al, 2017). Furthermore, the

upregulation on NK cells by NKG2A in patients with

lung cancers can act as a biomarker of tumor

metastatization (NK Cell Phenotypic Modulation in

Lung Cancer Environment, 2021). Besides, the direct

interaction between NK cells and intratumor stromal

cells gives rise to the pathogenic and phenotypic

mutation of NK cell in lung cancer as well as invasive

breast cancer where an increment in the expression of

NKG2A and a lessened expression of the NKRs

NKp30, NKG2D, DNAM-1, and CD16 have been

observed (Galland, Vuille, Martin, et al, 2017,

Mamessier, Sylvain, Thibult, et al, 2011).

2.2 The Ligand of NKG2A in Both NK

and T Cells

The primary ligand for CD94/NKG2A inhibitory

receptor is the human major histocompatibility

complex class Ib (MHC-Ib) molecule, HLA-E (Braud,

Allan, O’Callaghan, et al, Borrego, Ulbrecht, Weiss,

Coligan, Brooks, 1998,)

and its mouse ortholog Qa-1b

(Borst L, Burg SH van der, Hall T van. 2020). This

class Ib protein specifically binds and presents an

immensely associated set of nonameric peptides

generated from the signal sequences of class I

molecules (Braud, Allan, O’Callaghan, et al, 1998,

Braud, Yvonne Jones, McMichael. 1997, Lee, Llano,

Carretero, et al, 1998), which is different from class Ia

molecules that exhibit a broad range of peptide

ligands. In addition, it contains only two functional

alleles present in humans (the HLA-E*01:01 and the

HLA-E*01:03 variants

)

(Borst L, Burg SH van der,

Hall T van. 2020). These 2 alleles can be distinguished

from each other only by an individual amino acid at

position 107 which is arginine (01:01) or glycine

(01:03) (Borst L, Burg SH van der, Hall T van. 2020).

The expression of HLA-E is overall common whereas

relatively low in normal tissues with exceptions of

high level of expression in trophoblast cells in the

placenta and ductal epithelial cells in the testis and

epididymis due to the effect of HLA-E in immune

tolerance (Wei, Orr, 1990, van Hall, André,

Horowitz, et al, 2019). In contrast, the amount of

HLA-E exert on tumor cells are abnormally increased

in lung, kidney, pancreas, stomach, colon, head and

neck, liver, melanoma, prostate, and rectal tumor

tissues (van Montfoort, Borst, Korrer, et al, 2018,

Gooden, Lampen, Jordanova, et al, 2011). It has been

reported that high HLA-E expression can be

associated with a poor prognosis in colorectal

carcinoma, breast and ovarian carcinoma (Gooden,

Lampen, Jordanova, et al, 2011, Levy, Bianchini,

Von Euw, et al, 2008). Nevertheless, a favorable

connection between expression of HLA-E and

survival time has been recognized in patients with

glioblastoma (Kren, Slaby, Muckova, et al, 2011).

Joseph D.Miller et al have indicated that the

position 5 Arg side chain in HLA-E performs as a

dominant contact for interaction with CD94/NKG2A

receptor, which acts as one of the main contact

residues together with P8 amino acids for this

interaction (Miller, Weber, Ibegbu, Pohl, Altman,

Jensen, 2003). For mechanism, the tyrosine

phosphorylation of ITIMs and following recruitment

and activation of phosphatases (SHP-1 and SHP-2)

then characterizes the ligation of inhibitory receptors,

thus causing the inhibition of various NK cell-

mediated effector functions (Burshtyn, Scharenberg,

Wagtmann, et al, 1996). The length of amino acid

between the two ITIMs in NKG2A is about 25

peptides, which is regarded to be appropriate for the

occupation of tandem SH2 with phosphatases6. Also,

for the maximum phosphatase catalytic activity, it is

necessary to activate SH2 domains of SHP-1/-2

simultaneously (Pluskey, Wandless, Walsh,

ICBEB 2022 - The International Conference on Biomedical Engineering and Bioinformatics

1078

Shoelson, 1995). Previous discovery had shown that

HLA-E complexed to the peptide correlating to the

leader sequence peptide derived from HLA-G-bound

CD94-NKG2A has the affinity of 0.94 mM (Kaiser,

Barahmand-pour, Paulsene, Medley, Geraghty,

Strong, 2005) and the peptide structure was found to

affect binding affinity (Miller, Weber, Ibegbu, Pohl,

Altman, Jensen, 2003).

2.3 Current Statue of NKG2A in Basic

Research

Since CD94/NKG2A receptor is expressed by not

only NK cells but also a subsets of T cells such as

activated αβ CD8pos T-cells, 𝛾𝛿 T cells, and NK-

T cells34, the blockade of CD94/NKG2A can

effectively unleash the reactivity of immune cells

involving several types of cytotoxic lymphocytes

(Figure2)., resulting in triggering their antitumor

potentials and strengthening tumor control (Zaghi,

Calvi, Marcenaro, Mavilio, Di Vito, 2019).

Figure 2. The mechanism of NKG2A inhibitor for cancer

treatment

Monalizumab/IPH2201 is a humanized and

clinical stage anti-NKG2A monoclonal

antibody(mAb) which was initially developed in mice

(Zaghi, Calvi, Marcenaro, Mavilio, Di Vito, 2019). It

have revealed therapeutic effect on immunodeficient

mice with human leukemia (Effects of anti-NKG2A

antibody administration on leukemia and normal

hematopoietic cells, 2021), leading to its possibility of

its development in phase I-III clinical trials targeting

solid tumors and hematologic. According to the Tg32

mouse PK assay, the monalizumab has a binding

affinity of 48.1 ± 3.1nM, NK cell killing efficacy of

1.5 ± 0.78 μg/ml and an approximately 17-day plasma

PK half‐life in Tg32 mouse. It is recently investigated

for its efficacy and toxicity in the treatment of

different forms of cancers, such as gynecological and

squamous cell carcinoma of the head and neck

(SCCHN) (Spinosa, Musial‐Siwek, Presler, et al,

2021). Since CD94/NKG2A receptors usually co-

express with PD-1 (André, Denis, Soulas, et al, 2018),

monalizumab are recently examined with anti-PD(L)1

antibodies (durvalumab and nivolumab) (Spinosa,

Musial‐Siwek, Presler, et al, 2021), which have also

been registered in NIH gov.clinical trial

(https://clinicaltrials. gov/ct2/home)

3 CLINICAL APPLICATION OF

NKG2A INHIBITOR,

MONALIZUMAB

Nowadays, the safety and efficacy of monalizumab is

investigated and tested. A number of clinical trials for

the treatment of different types of cancer have already

completed and shown effective results, including

Gynecologic cancer (NCT02459301), colorectal

cancer (NCT02671435), recurrent or metastatic head

and neck cancer (NCT02643550) and chronic

lymphocytic leukemia (NCT02643550), also listed in

table1 (Table 1).

Table 1: Completed clinical trials related to monalizumab (IPH2201).

Target Drug

Pivotal

Indication

Trials

No.

Phase Most recent result

NKG2

Monalizumab

(IPH2201)

Gynecologic

cancer

NCT024

59301

Monolizumab (10 mg/kg i.v. every two weeks) is well

tolerated in individuals who have already been treated for

with gynecologic malignancies. There are mild related

adverse events and no dose-limiting cytotoxicity. Short-

term disease stabilization is observed.

PD-L1

NKG2

VEGF

EGFR

Durvalumab

Monalizumab

mFOLFOX6

Bevacizumab

Cetuximab

metastatic

microsatellite-

stable colorectal

cancer (MSS-

CRC)

NCT026

71435

1 and

In advanced/metastatic MSS-CRC, the combined therapy

had a manageable safety profile, with no dose-limiting

toxicity and DMCB showed promising preliminary

activity. Most of the patients treated give partial response

or have a chronic disease.

NKG2A: A Novel Immune Checkpoint Protein for Cancer Treatment

1079

NKG2

EGFR

Monalizumab

Cetuximab

recurrent or

metastatic head

and neck cancer

NCT026

43550

1 and

the combination of monalizumab and cetuximab is safe

for the patients with recurrent or metastatic head and neck

cancer. Most of the patients respond partially or have a

stable disease.

NKG2

monalizumab

Ibrutinib

Chronic

Lymphocytic

Leukemia

NCT025

57516

1/2

The combination of monalizumab and ibrutinib shows

dose-limiting toxicity. Most patients show partial response

or have a stable disease. The most common adverse events

is Diarrhea. Due to its termination, the results have not

een completed.

The purpose of NCT02459301 is to explore and

determine the recommended phase II dose (RP2D) of

monalizumab which is analyzed as a separate agent for

treatment for patients with advanced, recurrent, or

metastatic gynecologic malignancies and its clinical

activity, pharmacokinetics, pharmacodynamics,

safety, and immunogenicity (Tinker, Hirte,

Provencher, et al, 2019). The data from this trial

indicates the recommended dose to be 10 mg/kg every

2 weeks (Tinker, Hirte, Provencher, et al, 2019).

Moreover, although monalizumab solely did not

induce treatment responses, it shows promising

activities: short-term stabilization, minimal drug

toxicities and high treatment efficacy (Tinker, Hirte,

Provencher, et al, 2019). The clinical trials of

NCT02671435 combining monalizumab with

durvalumab (MEDI4736, anti-PD-L-1 mAb) which

also investigates solid tumors demonstrates favorable

results again. The toxicity and tolerability of

monalizumab as a single agent and in combination

with durvalumab had been tested in a non-responder

cancer to single-agent anti-PD-1/PD-L-1 therapy

called metastatic microsatellite-stable colorectal

cancer (MSS-CRC), (Wainberg, Diamond,

Curigliano, et al, 2020). The updated data confirms

the excellent tolerance of this therapy without dose-

limiting toxicity and the majority of participants

display partial responses or have stable diseases

(Wainberg, Diamond, Curigliano, et al, 2020).

Another clinical trial related to solid tumor is the trial

NCT02643550, a multicenter single arm study to

evaluate the combination of monalizumab and

cetuximab(anti-EGFR) in patients with recurrent

and/or metastatic head and neck cancer (R/M

SCCHN) (Cohen, Bauman, Salas, et al, 2020). The

preliminary data revealed the acceptable safety of this

therapy and early, deep and durable responses in

participants (Cohen, Bauman, Salas, et al, 2020). The

therapy showed encouragement of progress free

survival (PFS) and overall survival (OS) in both 10

naïve and 10 pretreated patients, as well as higher

activity in platinum-resistant, HPV positive and

negative patients than cetuximab alone based on

historical data (Cohen, Bauman, Salas, et al, 2020).

Importantly, these information warrant the increased

attempt of combination of monalizumab and

cetuximab in the treatment for SCCHN.

Different from these clinical trials studying solid

tumors, phase I/II clinical trial (NCT02557516) which

analyses the combination of monalizumab with

irutinib, a Bruton’s tyrosine kinase inhibitor already

used in the treatment of the Chronic Lymphocytic

Leukemia (CLL) which is a hematologic malignancy,

aims at seeking for a long-run therapeutic benefit for

patients suffering from CLL (Innate Pharma, 2021).

The trial was designed to justify the assumption that

the coeffect of ibrutinib and monalizumab will give

rise to complete response (CR) rate, particularly CR

without minimal residual disease (MRD), since this

has been proved to be correlated with permanent

clinical benefit (Innate Pharma, 2021). Unfortunately,

it had been terminated due to different factors

including adverse events, disease progression,

physician decision and sponsor decision (Innate

Pharma, 2021). But it still left valuable data: most of

the treated patients have a reverse event of diarrhea

and show partial responses or have a stable disease.

Furthermore, the result revealed dose-limiting toxicity

(Innate Pharma, 2021).

Apart from the clinical trials above, there are

several ongoing trials for the investigation of

monalizumab which are still enrolling patients (Table

2). Different combinations with anti-EGFR, anti-PD-

L1, morpholino-pyrimidine-based inhibitor and

chemotherapy are tested in different cancer

indications, including patients with unresectable stage

III NSCLC (NCT03822351) and patients with PD-1

therapy-resistant NSCLC (NCT03833440), as well as

resectable early-stage (II-IIIA) NSCLC, or patients

with advanced squamous cell carcinoma of the head

and neck (NCT04590963, NCT03088059), and also a

trial tested monalizumab alone in patients with

Advanced or Metastatic Hematological or Solid

Malignancies (NCT04333914).

ICBEB 2022 - The International Conference on Biomedical Engineering and Bioinformatics

1080

Table 2: The ongoing clinical trials related to monalizumab (IPH2201).

Target Drug Indication

Clinical trial

no.

Phase

Recruitment

status

First

posted

date

Last

update

posted

Estimated

Study

completion date

NKG2A

EGFR

Monalizumab

Cetuximab

Squamous

Cell

Carcinoma of

the Head and

Nec

NCT04590963 3 Recruiting

Oct.19

2020

Oct.29

2021

Mar.28

2024

PD-L1

CD73

NKG2A

Durvalumab

Oleclumab

Monalizumab

Stage III Non-

Small Cell

Lung Cancer

Unresectable

NCT03822351 2

Active, not

recruiting

Jan.30

2019

Aug.4

2021

Jul.11

2023

NKG2A Monalizumab

Advanced or

Metastatic

Hematological

or Solid

Tumo

NCT04333914 2

Active, not

recruiting

Apr.3

2020

Aug.5

2021

Dec.2021

PD-L1

CD73

NKG2A

Durvalumab

Oleclumab

Monalizumab

Non-small

Cell Lung

Cance

NCT05061550 2

Not yet

recruiting

Sept.29

2021

Sept.29

2021

Feb.19

2025

PD-L1

NKG2A

CD73

Durvalumab

Monalizumab

Oleclumab

Ceralasertib

Docetaxel

Non-small

Cell Lung

Cancer

NCT03833440 2 Recruiting

Feb.7

2019

Apr.1

2021

Feb.2024

NKG2A

EGFR

PD-L1

PD-1

Monalizumab

Cetuximab

Anti-PD(L)1

Head and

Neck

Neoplasms

NCT02643550 1,2

Active, not

recruiting

Dec.31

2015

Feb.9

2021

Sept,2022

NKG2A

PD-L1

Monalizumab

Duvalumab

Carcinoma,

Squamous

Cell of Head

and Nec

NCT03088059 2 Recruiting

Mar.23

2017

Nov.6

2019

Dec.2021

4 CONCLUSIONS

The main challenges of immunotherapy are to raise

the population of responding patients, as well as

overcoming tumor resistance (Borst L, Burg SH van

der, Hall T van. 2020). The NK cell and T cell

immunotherapy are fast-growing field with

remarkable contribution to cancer treatment. Here,

CD94/NKG2A, as a novel immune checkpoint protein

expressed on subsets of NK and T cells, has its

upregulation related to upregulation of its ligand,

HLA-E, and immune cell exhaustion. The abnormal

expression of both CD94/NKG2A and its ligand in

intratumor region is negatively correlated to cancer

prognosis, OS and DFS of patients, providing an idea

that blockade of the inhibitory receptor or its ligand

has the potential to unleash immunity against tumor

(Sun, Xu, Huang, et al, 2017, NK Cell Phenotypic

Modulation in Lung Cancer Environment, 2021,

Gooden, Lampen, Jordanova, et al, 2011, Levy,

Bianchini, Von Euw, et al, 2008, (Kren, Slaby,

Muckova, et al, 2011) Monalizumab is the humanized

NKG2A-targeting monoclonal antibody that is now

under investigation for its safety and efficacy. Data

from the results of clinical trials about various cancer

indication reveals its possibility and reliability as the

treatment for solid and hematologic malignancies,

especially in combination with other monoclonal

antibodies or cancer therapy.

ACKNOWLEDGMENTS

I thank my biological teacher, Xuan Zhang, for

provided me with some basic knowledge of cancer

treatment, and revised the manuscript.

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