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USING AN ANTAGONIST OF CHIMERIC RECEPTOR ANTIGEN T CELL THERAPY TO PREVENT
CYTOKINE STORM IN COVID
Zilefac Brian NGOKWE1,2*
,Tamoh
Stephane1,2, Cheboh Cho Fon1,2
, Kouamou Tchiekou Audrey
Audrey Sandra
1
Department of Oral Surgery, Maxillofacial Surgery and Periodontology, Faculty of Medicine and Biomedical
Sciences,
2
Post graduate school for Life, Health and Environmental Sciences,
ARTICLE INFO
ABSTRACT
SARS COV2 pandemic is almost 3 years old and remains a case
production of pro
clearance but also promotes paradoxically hyper
unfortunate event leading to organ failure
death. With the advent of new variants, the interaction between vaccinated and unvaccinated people
and also the interaction between persons with different variants or between the healthy and the
asymp
tomatic; all of these
achieved remarkable clinical results
CAR T and SARS COV 2 share one thing in common; the cytokine storm
treatment associated complication and the latter is an exaggerated host response. Hence, we propose
using Immunopharmacology (which targets amongst others, pathologies in which inflammation
main component), by using anti
objective to help alleviate these
lymphocytes as living drugs equipped with a CAR construct directed against TH2 or viral epitopes.
We hope to curb the severe complications and the poor outcomes(mortalities) associated with this
pathology
Copyright©2023, Zilefac Brian NGOKWE et al.
This
unrestricted use, distribution, and reproduction in any
medium,
INTRODUCTION
Coronaviruses in the last two decades have caused serious infection
and mortality in humans (1,2). SARSCoV-2,
is a
similar to two other
coronaviruses causing deadly infections
differences in sequences in the spike protein in SARS
in its enhanced binding to angiotensin-
converting enzyme 2 (ACE2)
in human lung cells (4). This
zoonotic disease, COVID
affected people's physical health, but also destroyed mental health and
floundered economic growth.(5,6)
Globally, as of February
there have been 757 264 511 confirmed cases of COVID
including 6 850 594de
aths, reported to WHO and a total of 13 222
459 780 vaccine doses have been administered
(
has been critical during
this pandemic, both for general guidelines and
for new scientific information; however, there is a fine line between
scie
ntifically accurate information and the brevity and simplicity with
which it should/could be communicated; sometimes trading accuracy
for simplicity may result in a message that is more confusing rather
than clarifying (8).
ISSN
: 0975
-
833X
Article History:
Received 14th January, 2023
Received in revised form
17th February, 2023
Accepted 105th March, 2023
Published online 18th April, 2023
Citation: Zilefac Brian NGOKWE,
Tamoh Stive Fokam, Ntep Ntep David Bienvenue, Nokam Kamdem Stephane, Cheboh Cho Fon
Audrey, Elage Epie Macbrain
Noubissie Audrey Sandra
cell therapy to prevent cytokine storm in COVID-
19: A hypothesis
Key words:
SARS COV2, CAR T, Cytokine Storm,
anti-CAR, TH2, Viral Epitopes, Poor
Outcomes.
*Corresponding Author:
Zilefac Brian NGOKWE
RESEARCH ARTICLE
USING AN ANTAGONIST OF CHIMERIC RECEPTOR ANTIGEN T CELL THERAPY TO PREVENT
CYTOKINE STORM IN COVID
-19: A HYPOTHESIS
,Tamoh
Stive Fokam1, Ntep
Ntep David Bienvenue
, Kouamou Tchiekou Audrey
1,2, Elage
Epie Macbrain
Audrey Sandra
1 and
Tamgnoue Guillaume Arthur
Department of Oral Surgery, Maxillofacial Surgery and Periodontology, Faculty of Medicine and Biomedical
Sciences,
University of Yaoundé I, Cameroon
Post graduate school for Life, Health and Environmental Sciences,
University of Yaoundé I
ABSTRACT
SARS COV2 pandemic is almost 3 years old and remains a case
production of pro
-
inflammatory cytokines in the context of COVID 19, not only impairs viral
clearance but also promotes paradoxically hyper
inflammation including cytokine storm; an
unfortunate event leading to organ failure
following long term damage due to inflammation and even
death. With the advent of new variants, the interaction between vaccinated and unvaccinated people
and also the interaction between persons with different variants or between the healthy and the
tomatic; all of these
possibly leading to the formation of new variants. CAR T therapy
achieved remarkable clinical results
treatment of relapsed/refractory B
CAR T and SARS COV 2 share one thing in common; the cytokine storm
treatment associated complication and the latter is an exaggerated host response. Hence, we propose
using Immunopharmacology (which targets amongst others, pathologies in which inflammation
main component), by using anti
-CAR-
engineered T to target the cytokine storm in COVID 19 with
objective to help alleviate these
symptoms or as a possible solution. Specifically, by using T
lymphocytes as living drugs equipped with a CAR construct directed against TH2 or viral epitopes.
We hope to curb the severe complications and the poor outcomes(mortalities) associated with this
pathology
.
This
is an open access article distributed under the Creative
Commons
medium,
provided the original work is properly cited.
Coronaviruses in the last two decades have caused serious infection
is a
beta-coronavirus,
coronaviruses causing deadly infections
(3) but
differences in sequences in the spike protein in SARS
-CoV-2 results
converting enzyme 2 (ACE2)
zoonotic disease, COVID
-19 not only
affected people's physical health, but also destroyed mental health and
Globally, as of February
21, 2023,
there have been 757 264 511 confirmed cases of COVID
-19,
aths, reported to WHO and a total of 13 222
(
7). Communication
this pandemic, both for general guidelines and
for new scientific information; however, there is a fine line between
ntifically accurate information and the brevity and simplicity with
which it should/could be communicated; sometimes trading accuracy
for simplicity may result in a message that is more confusing rather
Interestingly, there is
the principle of the iceberg in COVID 19, with
symptomatic patients consisting the visible part of the iceberg.
Different countries exhibit varying results and this could be due to
poor diagnostic tests, limited access to diagnostic tests to identify
affec
ted people in different countries and different percentages of
asymptomatic people with COVID 19 in various communities. Hence
the interaction between these groups of people could increase the
creation of new recombinant viruses which could be more harmfu
and more difficult to treat.
This possible interaction has been
demonstrated in a uniquely closed environment
interaction can be seen by the variants of concern (variants that have
been associated with an increase in the transmission or
COVID-
19) with the latest being variant B.1.1.529, commonly known
as Omicron (7,10–12)
. There are reports that vaccinated people made
up 42% of fatalities in January and February during omicron. that’s
compared with 23% at the peak of the
testament to this viewpoint in our opinion. However recent data
suggests that people who are vaccinated are 20 times less likely to be
hospitalized (13).
International Journal of Current Research
Vol. 15, Issue, 04, pp.24215-24219, April, 2023
DOI: https://doi.org/10.24941/ijcr.
44965
.04.2023
Tamoh Stive Fokam, Ntep Ntep David Bienvenue, Nokam Kamdem Stephane, Cheboh Cho Fon
Noubissie Audrey Sandra
and Tamgnoue Guillaume Arthur. 2023. “
Using an antagonist of Chimeric Receptor Antigen T
19: A hypothesis
.”. International Journal of Current Research, 15, (0
4
Available online at http://www.journalcra.com
z
USING AN ANTAGONIST OF CHIMERIC RECEPTOR ANTIGEN T CELL THERAPY TO PREVENT
Ntep David Bienvenue
1, Nokam Kamdem
Epie Macbrain
1, Noubissie
Tamgnoue Guillaume Arthur
1
Department of Oral Surgery, Maxillofacial Surgery and Periodontology, Faculty of Medicine and Biomedical
University of Yaoundé I
SARS COV2 pandemic is almost 3 years old and remains a case
for concern. An overwhelming
inflammatory cytokines in the context of COVID 19, not only impairs viral
inflammation including cytokine storm; an
following long term damage due to inflammation and even
death. With the advent of new variants, the interaction between vaccinated and unvaccinated people
and also the interaction between persons with different variants or between the healthy and the
possibly leading to the formation of new variants. CAR T therapy
has
treatment of relapsed/refractory B
-cell-derived malignancies.
CAR T and SARS COV 2 share one thing in common; the cytokine storm
even though the former is a
treatment associated complication and the latter is an exaggerated host response. Hence, we propose
using Immunopharmacology (which targets amongst others, pathologies in which inflammation
is the
engineered T to target the cytokine storm in COVID 19 with
symptoms or as a possible solution. Specifically, by using T
lymphocytes as living drugs equipped with a CAR construct directed against TH2 or viral epitopes.
We hope to curb the severe complications and the poor outcomes(mortalities) associated with this
Commons
Attribution License, which permits
the principle of the iceberg in COVID 19, with
symptomatic patients consisting the visible part of the iceberg.
Different countries exhibit varying results and this could be due to
poor diagnostic tests, limited access to diagnostic tests to identify
ted people in different countries and different percentages of
asymptomatic people with COVID 19 in various communities. Hence
the interaction between these groups of people could increase the
creation of new recombinant viruses which could be more harmfu
l
This possible interaction has been
demonstrated in a uniquely closed environment
(9). Also, this
interaction can be seen by the variants of concern (variants that have
been associated with an increase in the transmission or
mortality of
19) with the latest being variant B.1.1.529, commonly known
. There are reports that vaccinated people made
up 42% of fatalities in January and February during omicron. that’s
compared with 23% at the peak of the
delta wave.(13) This could be
testament to this viewpoint in our opinion. However recent data
suggests that people who are vaccinated are 20 times less likely to be
INTERNATIONAL JOURNAL
OF
CURRENT
RESEARCH
Tamoh Stive Fokam, Ntep Ntep David Bienvenue, Nokam Kamdem Stephane, Cheboh Cho Fon
, Kouamou Tchiekou
Using an antagonist of Chimeric Receptor Antigen T
4
), 24215-24219.
We strongly believe that primary prevention would have been the best
option in an ideal situation but we are far from been in one; due to
socio-economic difficulties (which could explain the disparity in
vaccinations between countries) and the enormous human interaction
given that the world is now a global village.
Figure 1. Iceberg principle in COVID 19
SARS-CoV-2 invades the host by virtue of angiotensin-converting
enzyme 2 (ACE2) receptors broadly distributed on various tissues and
immune cells (Yang, 2021; Kumar, 2022).(1,14) The virus can cause
a wide array of clinical manifestations ranging from mild to severe
forms with fatal outcomes. Evidence has demonstrated that
deterioration of COVID 19 may be due immunopathological damage.
Particularly, separate studies have reported that highly elevated levels
of pro-inflammatory cytokines are produced during the crosstalk
between epithelial cells and immune cells in COVID-19, which has
linked the cytokine storm (CS) with the severe complications and
poor outcomes in this infection. Due to their cytotoxic capacity, T
cells emerged as attractive candidates for specific immunotherapy of
cancer. A promising approach is the genetic modification of T cells
with chimeric antigen receptors (CARs) (15). The CAR-mediated
recognition induces cytokine production and tumor-directed
cytotoxicity of T cells (16) . Chimeric antigen receptor (CAR) T cell
therapy represents a paradigm shift in the management of pediatric B-
cell acute lymphoblastic leukemia (ALL) and adult B-cell non-
Hodgkin lymphomas (NHL) (17). There has been enormous progress
in genetic engineering in the last decades paving the way for the
development of CAR T cells.
CARs typically comprise an extracellular antigen recognition moiety
fused via a flexible hinge and transmembrane region to an
intracellular signaling unit, thereby combining the virtues of
antibodies (high antigen-binding specificity) and immune cells (potent
anti-tumor effector mechanisms) within one single fusion molecule
(1). Unfortunately, severe treatment-associated toxicities still restrain
the widespread application of this promising technology. The most
frequent side effects following CAR T-cell administration include
cytokine release syndrome (4–7), Given that organ injury in COVID
19 could be due to direct viral infection and immune overactivation,
we intend to prevent these by using anti-CAR T engineered T cells.
COVID-19 and cytokine storm release: Cytokine storm is the most
life-threatening complication associated with COVID-19,
characterized by a hyperactivated and proinflammatory state of the
immune system(18–20). Highlighting the importance of the immune
system in the physiopathology of this disease (20–22)
Sufficient evidence has revealed the components and characteristics
of CS in the patients with severe COVID-19, which are composed of
an array of cytokines (1). The initiation of COVID-CS induction
during infection and the predominant causative cytokine in COVID-
19 immunopathology remain largely unknown. Despite the lack of
definite pathogen associated molecule pattern (PAMP) of SARS-
CoV-2, in analogy with SARS-CoV and MERS-CoV, it can be
speculated that upon cellular entry of SARS-CoV-2 via its ACE2
receptor, viral genomic single-stranded RNA or other RNA
compositions (double-stranded RNA) as PAMPs can be sensed by the
related pattern recognition receptors (PRRs), in host cells.(1)
However, the protective IFN-I response is quickly and selectively
abrogated by SARS-CoV-2 via different mechanisms. This is
accompanied by an overwhelming production of pro-inflammatory
cytokines in the context of COVID-19, which not only impairs viral
clearance but also promotes paradoxical hyperinflammation including
CS. Therefore, from the immunology perspective, COVID-CS may be
an unfortunate event whereby the intended host immune response
combating the SARS-CoV-2 has lost control and transformed into an
inflammatory type. In SARS-CoV-2 infection, the virus infects the
respiratory epithelial tissue and activates local innate immune cells to
release inflammatory cytokines and other chemokines, which then
recruit more innate immune cells and activate adaptive immune cells
(CD4+ and CD8+ T cells) from the peripheral tissues to produce
sustained inflammatory which induce myelopoiesis and emergency
granulopoiesis that further aggravate lung and epithelial damage. In
addition, overproduction of systemic cytokines gives rise to anemia
through erythro-phagocytosis and macrophage activation as well as
causes perturbation of coagulation and vascular hemostasis, resulting
in capillary leak syndrome, thrombosis, and DIC. These events
together lead to ARDS, multiorgan failure, and death. It is worth
noting that, the host immunoregulatory system is usually capable of
retaining and fine-tuning the protective inflammation to an
appropriate level. Regulatory cells such as Tregs, can produce
regulatory cytokines like IL-10 and tumor growth factor-β to
antagonize overactivated immune responses. However, aggressive
inflammatory conditions such as CS cannot be calmed by the
regulatory system’s natural ability.
COVID-CS is a complicated and dynamic inflammatory process
caused by a group of cytokines from initiation, immune cell
hyperactivation, to organ dysfunction. The development of precise
therapeutic intervention in appropriate time is required to effectively
control COVID-CS. In principle, the treatment strategy is to control
ongoing inflammatory response by specifically or nonspecifically
targeting inflammatory cytokines or related signaling pathways and to
resume the host immunoregulatory system (1). Excessive local release
of cytokines is considered to be the determinant of pathological
alterations and the clinical manifestation of ARDS. Overall, the
primary pathological manifestations in the lung tissue are viral
cytopathic-like changes, infiltration of inflammatory cells, and the
presence of viral particles. Thus, severe lung injury in COVID-19
patients is considered as the result of both direct viral infection and
immune overactivation.(23)
CAR biochemistry and CAR therapy in current medicine:
Clinical research on adoptive transfer of T lymphocytes for infectious
and malignant disorders is quite active. The use of cells transduced
with T cell receptors (TCRs), in which tumor antigen recognition
occurs through presentation on cell surface human leukocyte antigens
(HLA), and the use of chimeric antigen receptors (CARs), which are
typically specified by a single-chain variable region domain of an
antibody and directed to a cell surface tumor-associated antigen, are
fundamental approaches to live T cell immune therapy (24). Chimeric
antigen receptor T cells (CAR T) are a promising type of
immunotherapy that uses genetically modified T cells to target cancer
cells. Several CAR T cell products have recently demonstrated
impressive efficacy against previously difficult-to-treat cancers.
Additionally, second-generation CARs include a CD28 or 4-1BB co-
stimulatory endodomain (25). Over the last few decades, there has
been tremendous progress in genetic engineering, paving the way for
the development of CAR T cells. CARs typically consist of an
extracellular antigen recognition moiety fused to an intracellular
signaling unit via a flexible hinge and transmembrane region,
combining the benefits of antibodies (high antigen-binding
specificity) and immune cells (potent anti-tumor effector
mechanisms) within a single fusion molecule (1). Immunotherapies
24216 Zilefac Brian NGOKWE et al. Using an antagonist of Chimeric receptor antigen t cell therapy to prevent cytokine storm in covid-19: A hypothesis
have showed promise, but they are far from flawless as evidenced
with certain serious treatment-associated toxicities. Unlike
conventional cytotoxic chemotherapy or small molecule inhibitors,
immunotherapies have specific toxicities that might be fatal, such as
cytokine release syndrome (CRS) and CAR-related encephalopathy
syndrome (CRES).(25)with cytokine release syndrome being the most
common side event after CAR T-cell administration (4–7). Several
strategies have been tested to counteract these effects, from non-
specific immunosuppression to selective CAR-engineered T cell
ablation. The latter technique is currently under huge research and is
based on the transgenic introduction of either suicide genes or
elimination marker genes. Following the introduction of these
therapeutic agents, selective CAR T-cell depletion is achieved
through complement-dependent cytotoxicity (CDC) and antibody-
dependent cellular cytotoxicity (ADCC). However, each method has
inherent limits that could prevent it from having a wide range of
therapeutic applications. These procedures also have serious
toxicities.
These include immunogenicity (21) the proposed depletion marker's
enormous size (more than 130 amino acids), the reliance on the
patients' immune systems (ADCC, CDC), and the occurrence of on-
target adverse effects brought on by mAb (monoclonal antibodies)
recognizing healthy tissue (22). The term CRS (cytokine release
syndrome) here refers to the excessive release of cytokines (IL-1, IL-
6, IFN-, and IL-10) by CAR-modified immune cells or bystander
innate immune cells (macrophages, monocytes, dendritic cells, and
other immune cells). Excess cytokines can result in vascular leakage,
respiratory failure, coagulopathy, and multi-organ system
dysfunction. The production of a significant amount of interferon
gamma (IFN-) and/or tumor necrosis factor alpha (TNF-) by CAR-T
activated cells, which in turn activates macrophages, dendritic cells,
and endothelial cells, is one possible cause causing CRS. These cells
can release more proinflammatory cytokines after being stimulated by
IFN- or TNF (8)
The perspective of CAR-T antagonist: This genetically modified T
cells that constitute the CAR T cells can induce a cytokine storm.
Control and reversal of toxicity have emerged as crucial components
of CAR T-cell treatment due to the extremely long-term survival and
proliferation capacity of genetically altered T cells (26). Bachmann et
al. suggested integrating a particular peptide epitope (E7B6) into the
CAR architecture that can be utilized as an intrinsic elimination tag as
a way to address this. This E-tag into the CAR's extracellular spacer
region should stop CAR T-cell escape, reducing the therapy's
cytotoxic effects while also increasing its safety (26). Therefore, for
selective and rigorous CAR T-cell elimination, Bachmann et al used a
short peptide epitope (E-tag) directly inserted into the CAR
architecture (26–28). Additionally, Bachmann et al sought to avoid
reliance on pharmacological drugs whose therapeutic effect invariably
declines due to their short half-life, which is a significant drawback,
by using T lymphocytes as living drugs that are equipped with a CAR
construct directed against a targetable portion of the therapeutic
CAR.(26)
With the other experiments, the cloning and structural characteristics
of conventional CARs as well as the universal chimeric antigen
receptor (UniCAR) 28/ζ construct with the incorporation of the
peptide epitope E7B6 (E-tag) as a targetable moiety in the
extracellular spacer region are described in detail (26,29–31). In the
hinge region of CARs, a peptide tag called E7B6 is recognized by the
αE-tag CAR construct. When an antigen is recognized, these αE-tag
CAR effector cells cross-link with target cells, which should cause the
elimination of the latter. Furthermore, Bachman et al demonstrated
that the cytotoxic effect was caused by the incorporated peptide's
specific recognition and binding. (αE-tag CAR). The anti-CAR
therapy has been demonstrated to prevent the cytotoxic effects due to
CAR T therapy and has been described in detail by Bachmann et
al.(26). Our hypothesis could act by targeting impaired viral clearance
and/or lymphocytes
Against viral infections, the adaptive immune system, particularly T
cells, plays an important role (32). T cell responses can be divided
into two types: effector cytotoxic cells (CTLs) and T helper cells (Th)
(20,33,34). Data suggest that cytokine storms may contribute to the
pathophysiology of severe COVID-19 disease together with reduced
Th1 antiviral adaptive responses.(35). Adults with COVID-19
experience acute peripheral T cell depletion, the degree of which is
positively correlated with the severity of the disease, whereas
asymptomatic patients and children typically retain peripheral T cell
numbers (36). The progression of the disease in COVID-19 has been
associated with the Th1 / Th2 balance. An appropriate Th1 immune
response, once a viral infection has been recognized, can eradicate it.
The cytokine storm that results from an overactive immune response
and increased cytokine production, however, leads to a Th2-type
response and a poor prognosis for COVID-19(36–38). In the same
light, research has demonstrated that elevated IL-15 levels and a
strong Th2 response are linked to the disease's deadly prognosis and
that senescent Th2 cell percentage was an independent risk factor for
death(20)
Also, COVID-19 patients had significantly fewer Th1 and more
highly activated Th2 cells than the reference population (20) . Th1
coordinated immune response during SARS-CoV-2 infection has been
associated with a good prognosis and resolution of COVID-19. The
type of Th response influenced disease outcome, as 78% of patients
who died had an over reactive Th2 response (20,39,40). Because their
cytokines stimulate antibody production, Th2 hyper activation could
explain why severe patients have higher antibody titers than mild or
asymptomatic patients (20,39,40). Moreover, within the cell, M.
Bacillus Calmette-Guerin (BCG) vaccination stimulates a Th1
response, guarding against the development of tuberculosis in
humans. With incredibly unexpected results, the effectiveness of the
BCG vaccine has been researched in COVID-19 patients. Patients
who received the vaccine and developed Th1 responses had lower
death and infection rates(41). A recent research, has emphasized the
significance of Th1 hypoactivation and Th2 overreaction, followed by
exhaustion, as they are related to a worse prognosis (20).
Hence by directing genetically modified anti-CAR T cells against
these lymphocytes (Th2) we hypothesize that this could limit or
prevent the cytokine storm. Also, could we direct these genetically
modified anti-CAR T cells against the viral epitopes to help limit or
prevent this cytokine storm. The SARS-CoV-2 virus is a single-
stranded enveloped positive-sense RNA virus that belongs to the β-
coronavirus (42,43). The proteins encoded by the genome of SARS-
CoV-2 are comprised of structural (SPs) and nonstructural proteins
(NSPs), as well as accessory proteins(44,45) . SPs mainly include
spike (S), membrane (M), envelope (E), and nucleocapsid (N)
proteins (42,46). The virus receptor-binding domain (RBD) contains
several antigenic epitopes. Those antigenic epitopes, also known as
antigenic determinants, are the binding sites of host antibodies. The
antigenic epitope plays an important role in activating the host CD4
and CD8 T cell immune response (47). Therefore, the S protein, the
RBD domain, and antigenic epitopes pave the road for the therapeutic
strategies (42). So by targeting these viral epitopes especially of the S
protein, we might to control the interactions and underlying
mechanisms between the host and virus infection. More so, research
has shown that SARS-CoV-2 uses the structural function of the S
protein to weaken or escape host immune surveillance (42). Hence by
creating a genetically modified CAR T antagonist, could help curb the
cytokine storm, given that thus aggressive inflammatory condition
(the cytokine storm) cannot be calmed by the regulatory system’s
natural ability and also given the non-precise nature of general
immunosuppression. We propose an antagonist for CAR-T (Chimeric
Receptor Antigen T cell) therapy as a solution to prevent cytokine
storm in patients with COVID-19 and hence reduce the morbidity and
mortality due to COVID 19.
CONCLUSION
The SARS-CoV-2 virus can cause a wide range of manifestations
from mild to severe/critical forms with fatal outcomes; fatal outcomes
with increased morbidities and mortalities which we aim to prevent.
24217 International Journal of Current Research, Vol. 15, Issue, 04, pp.
24215-24219, April, 2023
Cytokine storm during the COVID 19 infection is
This unfortunate event causes deaths due to ARDS and multi
failure CAR-
T therapies has as one of its effects inducing a cytokine
storm. So, by using immunopharmacology more precisely, a
genetically modified antagonist of this t
herapy; we intend to prevent
or curb the adverse effects caused by this cytokine storm which can
be helpful in severe SARS-CoV-2
to reduce the mortalities and
morbidities associated with this pandemic.
Figure 2.
Target; CAR T cells
Anti-CAR targets
selectively and precisely eliminates CAR T
with the help of its short peptide epitope.
Figure 3.
Target; Th2 lymphocytes or viral epitopes
We propose using a genetically modified anti-
CAR T cells against
Th2lymphocytes to prevent cytokine storm
or viral epitopes
Acknowledgements
: Dr Ronit Sionov (Hebrew University of
Jerusalem)
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24219 International Journal of Current Research, Vol. 15, Issue, 04, pp.
24215-24219, April, 2023
