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Research Article
A Questionnaire On Adoptive Cell Therapy Among Syrian Medical Students
Harfouch RM*, Alhouri AL and Salloum A
Department of Biochemistry and Microbiology, Faculty of Pharmacy, Al Andalus University, Tartous, Syria
*
Corresponding author:
Rim M. Harfouch,
Department of Biochemistry and Microbiology,
Faculty of Pharmacy, Al Andalus University,
Tartous, Syria, E-mail: rimharfouch@u.edu.sy
Received: 29 Apr 2021
Accepted: 12 May 2021
Published: 18 May 2021
Copyright:
©2021 Harfouch RM. This is an open access article dis-
tributed under the terms of the Creative Commons Attri-
bution License, which permits unrestricted use, distribu-
tion, and build upon your work non-commercially.
Citation:
Harfouch RM. A Questionnaire On Adoptive Cell Thera-
py Among Syrian Medical Students. Ann Clin Med Case
Rep. 2021; V6(15): 1-5
http://www.acmcasereport.com/ 1
Annals of Clinical and Medical
Case Reports
ISSN 2639-8109 Volume 6
Keywords:
Questionnaire; Adoptive cell therapy; Tumor-infil-
trating lymphocytes (TIL); PBMCs
1. Abstract
Adoptive Cell Therapy (ACT) is a type of immunotherapy, in
which immune cells are implanted in patients to help them cure
diseases (such as cancer). It is a new technique that has proven its
effectiveness in treating different types of cancer, especially mel-
anoma, breast cancer, and colon cancer. It has many factors that
distinguish it from other cancer treatments, such as its selectivity
towards cancer cells without harming normal body cells, therefore
less side effects.
We aimed in this questionnaire to evaluate the knowledge of med-
ical students in Syria on this new technique, it included (822) par-
ticipants, mainly students and graduates from medical faculties
and others who have interests in the medical field or are informed
about it. The questionnaire involved questions about ACT, if the
participants were familiar with it or heard of it before, if they were
familiar with other cancer treatments, and many other questions.
It was evident from the results that the participants were more fa-
miliar with chemotherapy and trusted it the most, as for ACT, few
have heard of it, and many thought it is unlikely to be applied in
Syria due to many obstacles.
2. Introduction
Adoptive Cell Therapy (ACT) is a type of immunotherapy, in
which immune cells are implanted in patients to help them cure
diseases (such as cancer). Many types of immune cells can be used
in Adoptive cell therapy, they can be either taken from the patient’s
own blood, tumor tissue, or from another donor. They are then
grown in large numbers in vitro and activated using different tech-
niques. After that they are infused back in the patient’s body to
help fight the cancer cells.
It had been noticed that in vitro modifying of the immune cells
such as T-cells would make them more effective and selective to
the antigens of the tumor cell. While the treatment is still under
study, each year new discoveries are being made involving it and
more obstacles are being overcome. [1-3]
2.1. Adoptive Cell Therapy with Genetically Engineered
T-Cells
T-cells can recognize tumor cells with TCR (T-cell receptor), but
this action is not effective enough to stop the tumor spreading or
killing the cancer cells. Scientists found that the anti-tumor action
can be improved when TCRs are genetically engineered.
Another way has been discovered to improve the effectiveness of
T-cells, which is replacing the TCR with CAR (chimeric antigen
receptor), then cultivating the engineered cells in large numbers
and implanting them back in the patients. These new cells can im-
mediately recognize cancer cells and attack them. [4-6]
2.2. Adoptive Cell Therapy with Tumor-Infiltrating Lympho-
cytes (Tils)
Tumor infiltrating lymphocytes are white blood cells that leach
and invade the tumor. TILs express the body’s natural response
against a cancerous tumor, through their ability to identify cancer
cells, which possess TAAs (tumor-associated antigens) and then
destroy them as if they were foreign bodies.
TIL scan be isolated from a fresh tumor sample and cultivated in
large numbers in vivo. This technique has been very effective in
the treatment of metastatic melanoma, and it can be used in many
tumors and conditions such as colon cancer. [7-9]
http://www.acmcasereport.com/ 2
Volume 6 Issue 15 -2021 Reserach Article
Figure 1: Academic specialization of the participants.
Figure 2: Cancer treatments the participants are familiar with
Figure 3: Percentage of participants that have heard about/are familiar with ACT
http://www.acmcasereport.com/ 3
Volume 6 Issue 15 -2021 Reserach Article
Figure 4: Percentage of participants who find ACT as a viable treatment
Figure 5: Percentage of participants that believe ACT is applicable in Syria
2.3. Treating with Adoptive Cell Therapy Using Peripheral
Blood Mononuclear Cells (Pbmcs)
PBMCs have been used as a source for the cells used in ACT for
3 decades because they are easy to isolate, and available in abun-
dance. They develop from different cells, including lymphocytes
(T cells, B cells, and the natural killer cells), monocytes, and the
dendritic cells. They can be activated using more than one method,
like genetic modification. By activating these cells using high dos-
es of IL-2, we get lymphokine-activated killer cells (LAK), which
are used to create the cytokine-induced killer cells (CIKs). [10]
2.4. Adoptive Cell Therapy with Cytokine-Induced Killer Cells
(CIK’s)
CIKs are considered the grandchild of LAKs, since they are easier
to get and more effective, and do not show any toxicity for normal
tissue cells. Studies have confirmed that these cells can be used to
treat colorectal cancer safely, guaranteeing a good effect. [11,12]
2.5. Adoptive Cell Therapy with Natural Killer Cells:
Natural killer cells belong to the innate immune system which form
the most important defense line for humans against pathogens and
mutant cells, and the significant feature for these cells, is express-
ing CD56 and/or CD16 but without the complex TCR-CD3.
These cells can recognize mutant or pathogen cells through spe-
cific antigens, whereas they can coordinate their job through the
integration between the activating and deactivating signals of the
receptors found on their surface, which lead to activating the nat-
ural killer cells.
Volume 6 Issue 15 -2021 Reserach Article
http://www.acmcasereport.com/ 4
These activating and deactivating receptors are considered respon-
sible for these cells’ ability to recognize abnormal cells and kill
them, they are also responsible for the cells’inability to kill normal
cells. [13-15]
3. Material and Methods
We made an electronic questionnaire about adoptive cell therapy
and other cancer treatments in general, it included hundreds of par-
ticipants (822 participants), mainly students and graduates from
medical faculties (pharmacy, medicine, dentistry, medical engi-
neering) and others who have an interest in the medical field or are
informed about it [16].
4. Results
And the results were as shown below:
Percentage of participants according to their academic specializa-
tion:
1. The category “other” includes dentistry which reached
70%, medical engineering which reached 15%, and col-
lege students whom are interested in medical affairs and
modern therapy techniques reached a percentage of 15%.
2. The participants were asked about the different cancer
treatments they were familiar with and the results are rep-
resented in the diagram below: And as we can see –as ex-
pected- that chemotherapy is the most commonly known
therapy in Syria, followed directly by surgical treatment,
which is followed by radiation therapy.
3. The participants were then asked if they knew aboutACT,
or if they heard of it before, and as we can see, the major-
ity have not heard about this treatment technique before:
4. Then we asked the participants who answered “yes” to
the previous question, what exactly do they know exactly
about this technique and the extent of their knowledge of
it: And the majority of their answers (92%) said that their
knowledge of it was shallow and limited on some general
information about this technique, since they don’t know
the complete procedure, but only that it is one of the im-
munological techniques used for cancer treatment.
5. After that we made a discussion for the participants, and
we asked them based on their point of view, what is the
most effective cancer treatment technique used nowa-
days? And we noticed that chemotherapy took first place
according to the participants based on trust and effective-
ness, followed by surgical treatment, then radiation ther-
apy, and finally immunotherapy.
6. We created a definition for ACT: Adoptive cell therapy is
a form of immunological technique for cancer treatment,
in which lymphocytes are isolated, proliferated, and mod-
ified in vitro until it gains the ability to recognize tumor
cells and target them, after that, the modified lympho-
cytes are injected back into the patient’s body where they
attack the tumor and treat it.After that, we asked them, if
they expect ACT to be a significant technique and a new
hope for cancer treatment, and the results were as shown
below:
7. We asked the participants about their opinion on the pos-
sibility of applying ACT in Syria, and the answers were
as shown below:
8. We discussed the obstacles that can face the possibility
of applying ACT in Syria. with the participants. In their
opinion, the biggest and most important obstacle was the
high material cost of this technique and the lack of experts
and equipment in the country due to war circumstances;
they also confirmed that the lack of scientific research and
interest in researchers has a big effect on this issue.
5. Conclusion
Adoptive cell therapy is a new promising strategy to reactivate the
immune system to fight cancer cells. Third world countries lack
the new techniques to make a research on humans, so we aimed of
this questionnaire to measure the knowledge of Syrian society, es-
pecially health practitioners and medical students, about adoptive
cell therapy to treat different types of cancer
6. Acknowledgment
Many thanks to Dr. Jamil Daher for his great efforts in revision of
our manuscript.
References
1. Cohen JE, Merims S, Frank S, Engelstein R, Peretz T, Lotem M.
Adoptive cell therapy: past, present and future. Immunotherapy.
2017; 9(2): 183-196.
2. Pages F, Galon J, Dieu-Nosjean MC, Tartour E, SautesFridman C,
Fridman WH. Immune infiltration in human tumors: a prognostic
factor that should not be ignored. Oncogene. 2010; 29(8): 1093-
1102.
3. Fefer A, Einstein AB, Cheever MA. Adoptive chemoimmunother-
apy of cancer in animals: a review of results, Ann. NY Acad. Sci.
1976; 277(00): 492-504.
4. Yang James C and Steven A. Rosenberg. Adoptive T-cell therapy for
cancer. Advances in immunology. Vol. 130. Academic Press, 2016;
130: 279-294.‫‏‬
5. Wrzesinski C, Paulos CM, Kaiser A, Muranski P, Palmer DC, Gat-
tinoni L, et al. Increased intensity lymphodepletion enhances tumor
treatment efficacy of adoptively transferred tumor-specific T cells. J
Immunother 2010; 33: 1-7.
6. Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS,
Phan GQ, et al. Durable complete responses in heavily pretreated
patients with metastatic melanoma using T-cell transfer immuno-
therapy. Clin Cancer Res. 2011; 17: 4550-7.
7. Cole DJ, Taubenberger JK, Pockaj BA, Yannelli JR, Carter C, Car-
rasquillo J, et al. Histopathological analysis of metastatic melano-
Volume 6 Issue 15 -2021 Reserach Article
http://www.acmcasereport.com/ 5
ma deposits in patients receiving adoptive immunotherapy with tu-
morinfiltrating lymphocytes. Cancer Immunol. Immunother. 1994;
38(5): 299-303.
8. Shen X, Zhou J, Hathcock KS, Robbins P, Powell DJ, Rosenberg
SA, et al. Persistence of tumor infiltrating lymphocytes in adoptive
immunotherapy correlates with telomere length. J. Immunother.
2007; 30(1): 123-129.
9. Radvanyi LG, Bernatchez C, Zhang M, Fox PS, Miller P, Chacon J,
et al. Specific lymphocyte subsets predict response to adoptive cell
therapy using expanded autologous tumor-infiltrating lymphocytes
in metastatic melanoma patients. Clin. Cancer Res. 2012; 18(24):
6758-6770.
10. Fan Jiaqiao, Shang D, Han B, Song J, Chen H, Yang J. Adoptive
cell transfer: Is it a promising immunotherapy for colorectal cancer?.
Theranostics. 2018; 8(20): 5784-5800.
11. Schlimper C, Hombach AA, Abken H, Schmidt-Wolf IG. Improved
activation toward primary colorectal cancer cells by antigen-specific
targeting autologous cytokine-induced killer cells. Clin Dev Immu-
nol. 2012; 2012: 238924.
12. Zoll B, Lefterova P, Csipai M, Finke S, Trojaneck B, Ebert O, et al.
Generation of cytokine-induced killer cells using exogenous inter-
leukin-2,-7 or-12. Cancer Immunol Immunother. 1998; 47: 221-26.
13. Veluchamy JP, Spanholtz J, Tordoir M, Thijssen VL, Heideman
DA, Verheul HM, et al. Combination of NK cells and cetuximab to
enhance anti-tumor responses in RAS mutant metastatic colorectal
cancer. PLoS One. 2016; 11: e0157830.
14. Edsparr K, Basse PH, Goldfarb RH, Albertsson P. Matrix metallo-
proteinases in cytotoxic lymphocytes impact on tumour infiltration
and immunomodulation. Cancer Microenviron. 2011; 4: 351-60.
15. Song X, Hong SH, Kwon WT, Bailey LM, Basse P, Bartlett DL, et
al. Secretory TRAIL-armed natural killer cell–based therapy: in vi-
tro and in vivo colorectal peritoneal carcinomatosis xenograft. Mol
Cancer Ther. 2016; 15: 1591-601.
16. Harfouch RM, Alhouri AL, Salloum A. Adoptive Cell Therapy: The
Syrian Community Knowledge. Ann Clin Cases. 2020; 1(3): 1016.

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A Questionnaire On Adoptive Cell Therapy Among Syrian Medical Students

  • 1. Research Article A Questionnaire On Adoptive Cell Therapy Among Syrian Medical Students Harfouch RM*, Alhouri AL and Salloum A Department of Biochemistry and Microbiology, Faculty of Pharmacy, Al Andalus University, Tartous, Syria * Corresponding author: Rim M. Harfouch, Department of Biochemistry and Microbiology, Faculty of Pharmacy, Al Andalus University, Tartous, Syria, E-mail: rimharfouch@u.edu.sy Received: 29 Apr 2021 Accepted: 12 May 2021 Published: 18 May 2021 Copyright: ©2021 Harfouch RM. This is an open access article dis- tributed under the terms of the Creative Commons Attri- bution License, which permits unrestricted use, distribu- tion, and build upon your work non-commercially. Citation: Harfouch RM. A Questionnaire On Adoptive Cell Thera- py Among Syrian Medical Students. Ann Clin Med Case Rep. 2021; V6(15): 1-5 http://www.acmcasereport.com/ 1 Annals of Clinical and Medical Case Reports ISSN 2639-8109 Volume 6 Keywords: Questionnaire; Adoptive cell therapy; Tumor-infil- trating lymphocytes (TIL); PBMCs 1. Abstract Adoptive Cell Therapy (ACT) is a type of immunotherapy, in which immune cells are implanted in patients to help them cure diseases (such as cancer). It is a new technique that has proven its effectiveness in treating different types of cancer, especially mel- anoma, breast cancer, and colon cancer. It has many factors that distinguish it from other cancer treatments, such as its selectivity towards cancer cells without harming normal body cells, therefore less side effects. We aimed in this questionnaire to evaluate the knowledge of med- ical students in Syria on this new technique, it included (822) par- ticipants, mainly students and graduates from medical faculties and others who have interests in the medical field or are informed about it. The questionnaire involved questions about ACT, if the participants were familiar with it or heard of it before, if they were familiar with other cancer treatments, and many other questions. It was evident from the results that the participants were more fa- miliar with chemotherapy and trusted it the most, as for ACT, few have heard of it, and many thought it is unlikely to be applied in Syria due to many obstacles. 2. Introduction Adoptive Cell Therapy (ACT) is a type of immunotherapy, in which immune cells are implanted in patients to help them cure diseases (such as cancer). Many types of immune cells can be used in Adoptive cell therapy, they can be either taken from the patient’s own blood, tumor tissue, or from another donor. They are then grown in large numbers in vitro and activated using different tech- niques. After that they are infused back in the patient’s body to help fight the cancer cells. It had been noticed that in vitro modifying of the immune cells such as T-cells would make them more effective and selective to the antigens of the tumor cell. While the treatment is still under study, each year new discoveries are being made involving it and more obstacles are being overcome. [1-3] 2.1. Adoptive Cell Therapy with Genetically Engineered T-Cells T-cells can recognize tumor cells with TCR (T-cell receptor), but this action is not effective enough to stop the tumor spreading or killing the cancer cells. Scientists found that the anti-tumor action can be improved when TCRs are genetically engineered. Another way has been discovered to improve the effectiveness of T-cells, which is replacing the TCR with CAR (chimeric antigen receptor), then cultivating the engineered cells in large numbers and implanting them back in the patients. These new cells can im- mediately recognize cancer cells and attack them. [4-6] 2.2. Adoptive Cell Therapy with Tumor-Infiltrating Lympho- cytes (Tils) Tumor infiltrating lymphocytes are white blood cells that leach and invade the tumor. TILs express the body’s natural response against a cancerous tumor, through their ability to identify cancer cells, which possess TAAs (tumor-associated antigens) and then destroy them as if they were foreign bodies. TIL scan be isolated from a fresh tumor sample and cultivated in large numbers in vivo. This technique has been very effective in the treatment of metastatic melanoma, and it can be used in many tumors and conditions such as colon cancer. [7-9]
  • 2. http://www.acmcasereport.com/ 2 Volume 6 Issue 15 -2021 Reserach Article Figure 1: Academic specialization of the participants. Figure 2: Cancer treatments the participants are familiar with Figure 3: Percentage of participants that have heard about/are familiar with ACT
  • 3. http://www.acmcasereport.com/ 3 Volume 6 Issue 15 -2021 Reserach Article Figure 4: Percentage of participants who find ACT as a viable treatment Figure 5: Percentage of participants that believe ACT is applicable in Syria 2.3. Treating with Adoptive Cell Therapy Using Peripheral Blood Mononuclear Cells (Pbmcs) PBMCs have been used as a source for the cells used in ACT for 3 decades because they are easy to isolate, and available in abun- dance. They develop from different cells, including lymphocytes (T cells, B cells, and the natural killer cells), monocytes, and the dendritic cells. They can be activated using more than one method, like genetic modification. By activating these cells using high dos- es of IL-2, we get lymphokine-activated killer cells (LAK), which are used to create the cytokine-induced killer cells (CIKs). [10] 2.4. Adoptive Cell Therapy with Cytokine-Induced Killer Cells (CIK’s) CIKs are considered the grandchild of LAKs, since they are easier to get and more effective, and do not show any toxicity for normal tissue cells. Studies have confirmed that these cells can be used to treat colorectal cancer safely, guaranteeing a good effect. [11,12] 2.5. Adoptive Cell Therapy with Natural Killer Cells: Natural killer cells belong to the innate immune system which form the most important defense line for humans against pathogens and mutant cells, and the significant feature for these cells, is express- ing CD56 and/or CD16 but without the complex TCR-CD3. These cells can recognize mutant or pathogen cells through spe- cific antigens, whereas they can coordinate their job through the integration between the activating and deactivating signals of the receptors found on their surface, which lead to activating the nat- ural killer cells.
  • 4. Volume 6 Issue 15 -2021 Reserach Article http://www.acmcasereport.com/ 4 These activating and deactivating receptors are considered respon- sible for these cells’ ability to recognize abnormal cells and kill them, they are also responsible for the cells’inability to kill normal cells. [13-15] 3. Material and Methods We made an electronic questionnaire about adoptive cell therapy and other cancer treatments in general, it included hundreds of par- ticipants (822 participants), mainly students and graduates from medical faculties (pharmacy, medicine, dentistry, medical engi- neering) and others who have an interest in the medical field or are informed about it [16]. 4. Results And the results were as shown below: Percentage of participants according to their academic specializa- tion: 1. The category “other” includes dentistry which reached 70%, medical engineering which reached 15%, and col- lege students whom are interested in medical affairs and modern therapy techniques reached a percentage of 15%. 2. The participants were asked about the different cancer treatments they were familiar with and the results are rep- resented in the diagram below: And as we can see –as ex- pected- that chemotherapy is the most commonly known therapy in Syria, followed directly by surgical treatment, which is followed by radiation therapy. 3. The participants were then asked if they knew aboutACT, or if they heard of it before, and as we can see, the major- ity have not heard about this treatment technique before: 4. Then we asked the participants who answered “yes” to the previous question, what exactly do they know exactly about this technique and the extent of their knowledge of it: And the majority of their answers (92%) said that their knowledge of it was shallow and limited on some general information about this technique, since they don’t know the complete procedure, but only that it is one of the im- munological techniques used for cancer treatment. 5. After that we made a discussion for the participants, and we asked them based on their point of view, what is the most effective cancer treatment technique used nowa- days? And we noticed that chemotherapy took first place according to the participants based on trust and effective- ness, followed by surgical treatment, then radiation ther- apy, and finally immunotherapy. 6. We created a definition for ACT: Adoptive cell therapy is a form of immunological technique for cancer treatment, in which lymphocytes are isolated, proliferated, and mod- ified in vitro until it gains the ability to recognize tumor cells and target them, after that, the modified lympho- cytes are injected back into the patient’s body where they attack the tumor and treat it.After that, we asked them, if they expect ACT to be a significant technique and a new hope for cancer treatment, and the results were as shown below: 7. We asked the participants about their opinion on the pos- sibility of applying ACT in Syria, and the answers were as shown below: 8. We discussed the obstacles that can face the possibility of applying ACT in Syria. with the participants. In their opinion, the biggest and most important obstacle was the high material cost of this technique and the lack of experts and equipment in the country due to war circumstances; they also confirmed that the lack of scientific research and interest in researchers has a big effect on this issue. 5. Conclusion Adoptive cell therapy is a new promising strategy to reactivate the immune system to fight cancer cells. Third world countries lack the new techniques to make a research on humans, so we aimed of this questionnaire to measure the knowledge of Syrian society, es- pecially health practitioners and medical students, about adoptive cell therapy to treat different types of cancer 6. Acknowledgment Many thanks to Dr. Jamil Daher for his great efforts in revision of our manuscript. References 1. Cohen JE, Merims S, Frank S, Engelstein R, Peretz T, Lotem M. Adoptive cell therapy: past, present and future. Immunotherapy. 2017; 9(2): 183-196. 2. Pages F, Galon J, Dieu-Nosjean MC, Tartour E, SautesFridman C, Fridman WH. Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene. 2010; 29(8): 1093- 1102. 3. Fefer A, Einstein AB, Cheever MA. Adoptive chemoimmunother- apy of cancer in animals: a review of results, Ann. NY Acad. Sci. 1976; 277(00): 492-504. 4. Yang James C and Steven A. Rosenberg. Adoptive T-cell therapy for cancer. Advances in immunology. Vol. 130. Academic Press, 2016; 130: 279-294.‫‏‬ 5. Wrzesinski C, Paulos CM, Kaiser A, Muranski P, Palmer DC, Gat- tinoni L, et al. Increased intensity lymphodepletion enhances tumor treatment efficacy of adoptively transferred tumor-specific T cells. J Immunother 2010; 33: 1-7. 6. Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immuno- therapy. Clin Cancer Res. 2011; 17: 4550-7. 7. Cole DJ, Taubenberger JK, Pockaj BA, Yannelli JR, Carter C, Car- rasquillo J, et al. Histopathological analysis of metastatic melano-
  • 5. Volume 6 Issue 15 -2021 Reserach Article http://www.acmcasereport.com/ 5 ma deposits in patients receiving adoptive immunotherapy with tu- morinfiltrating lymphocytes. Cancer Immunol. Immunother. 1994; 38(5): 299-303. 8. Shen X, Zhou J, Hathcock KS, Robbins P, Powell DJ, Rosenberg SA, et al. Persistence of tumor infiltrating lymphocytes in adoptive immunotherapy correlates with telomere length. J. Immunother. 2007; 30(1): 123-129. 9. Radvanyi LG, Bernatchez C, Zhang M, Fox PS, Miller P, Chacon J, et al. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clin. Cancer Res. 2012; 18(24): 6758-6770. 10. Fan Jiaqiao, Shang D, Han B, Song J, Chen H, Yang J. Adoptive cell transfer: Is it a promising immunotherapy for colorectal cancer?. Theranostics. 2018; 8(20): 5784-5800. 11. Schlimper C, Hombach AA, Abken H, Schmidt-Wolf IG. Improved activation toward primary colorectal cancer cells by antigen-specific targeting autologous cytokine-induced killer cells. Clin Dev Immu- nol. 2012; 2012: 238924. 12. Zoll B, Lefterova P, Csipai M, Finke S, Trojaneck B, Ebert O, et al. Generation of cytokine-induced killer cells using exogenous inter- leukin-2,-7 or-12. Cancer Immunol Immunother. 1998; 47: 221-26. 13. Veluchamy JP, Spanholtz J, Tordoir M, Thijssen VL, Heideman DA, Verheul HM, et al. Combination of NK cells and cetuximab to enhance anti-tumor responses in RAS mutant metastatic colorectal cancer. PLoS One. 2016; 11: e0157830. 14. Edsparr K, Basse PH, Goldfarb RH, Albertsson P. Matrix metallo- proteinases in cytotoxic lymphocytes impact on tumour infiltration and immunomodulation. Cancer Microenviron. 2011; 4: 351-60. 15. Song X, Hong SH, Kwon WT, Bailey LM, Basse P, Bartlett DL, et al. Secretory TRAIL-armed natural killer cell–based therapy: in vi- tro and in vivo colorectal peritoneal carcinomatosis xenograft. Mol Cancer Ther. 2016; 15: 1591-601. 16. Harfouch RM, Alhouri AL, Salloum A. Adoptive Cell Therapy: The Syrian Community Knowledge. Ann Clin Cases. 2020; 1(3): 1016.