Alpha-Fetoprotein Binds Toxins and Can Be Used to Treat Cancer

Main Article Content

Vladimir N. Pak

Abstract

The inefficiency of the immune system to kill cancer cells leads to the disease. Like in pregnancy, oncofetal proteins counteract the immune attack. Alpha-fetoprotein is an immunosuppressive protein generated by the embryo and in insignificant amounts by adults. It delivers nutrients to embryo cells and to the monocytes that suppress both innate and adaptive immunity during pregnancy and cancer. The small subpopulation of suppressor monocytes and cancer cells absorb the alpha-fetoprotein-nutrient complex through the specific receptor that is mostly absent in normal adult cells. It comes out that suppressor monocytes are the main targets in cancer prophylactic or treatment, not cancer cells. By delivering toxins instead of nutrients alpha-fetoprotein kills suppressor monocytes canceling immune suppression, as well as killing cancer cells directly. It is the perfect synergy of the most powerful cancer immunotherapy with targeted chemotherapy. Alpha-fetoprotein chemical conjugates, as well as the complexes of this oncofetal protein with binding toxins, have shown promising results in cancer treatments. Oral porcine alpha-fetoprotein complexes with toxins can prevent and/or treat cancer, although their immunotherapy mechanism of action is undiscovered.

Article Details

How to Cite
PAK, Vladimir N.. Alpha-Fetoprotein Binds Toxins and Can Be Used to Treat Cancer. Medical Research Archives, [S.l.], v. 10, n. 10, oct. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3236>. Date accessed: 06 dec. 2022. doi: https://doi.org/10.18103/mra.v10i10.3236.
Section
Research Articles

References

1. Gabrilovich DI. Myeloid-Derived Suppressor Cells. Cancer Immunol Res. 2017;5(1): 3–8. doi.org/10.1158/2326-6066.CIR-16-0297.
2. Pawelec G, Verschoor CP, Ostrand-Rosenberg S. Myeloid-Derived Suppressor Cells: Not Only in Tumor Immunity. Front Immunol. 2019; (15) 10:1099. doi: 10.3389/fimmu.2019.01099.
3. Zhang S, Ma X, Zhu Ch, Liu L, Wang G, Yuan X. The Role of Myeloid-Derived Suppressor Cells in Patients with Solid Tumors: A Meta-Analysis. PloS One. 2016; 11 (10): e0164514. doi.org/10.1371/journal.pone.0164514.
4. Kwak T, Wang F, Deng H, et al. Distinct populations of immune-suppressive macrophages differentiate from monocytic myeloid-derived suppressor Cells in Cancer. Cell Rep. 2020;33, 108571. doi: 10.1016/j.celrep.2020.108571.
5. Jørgensen N, Persson G, Hviid TVF. The Tolerogenic Function of Regulatory T Cells in Pregnancy and Cancer. Front. Immunol. 2019;10 (May): 911. doi.org/10.3389/fimmu.2019.00911.
6. Ostrand-Rosenberg S, Fenselau C. Myeloid-Derived Suppressor Cells: Immune-Suppressive Cells That Impair Antitumor Immunity and Are Sculpted by Their Environment. J. of Immunol. 2018; 200 (2): 422–431. doi.org/10.4049/jimmunol.1701019.
7. Tumino N, Besi F, Martini S, et al. Polymorphonuclear Myeloid-Derived Suppressor Cells Are Abundant in Peripheral Blood of Cancer Patients and Suppress Natural Killer Cell Anti-Tumor Activity. Front. Immunol. 2022; 12:803014. doi: 10.3389/fimmu.2021.803014.
8. Najjar YG, Finke JH. Clinical Perspectives on Targeting of Myeloid Derived Suppressor Cells in the Treatment of Cancer. Front. Oncol. 2013;3: 49. doi.org/10.3389/fonc.2013.00049.
9. Jiménez-Cortegana C, Galassi C, Klapp V, Gabrilovich DI, Galluzzi L. Myeloid-Derived Suppressor Cells and Radiotherapy. Cancer Immunol Res. 2022; May 3;10(5):545-557. doi: 10.1158/2326-6066.CIR-21-1105.
10. Anger N, Rossowska J. Myeloid-derived suppressor cells as a target for anticancer therapy. Postępy Higieny i Medycyny Doświadczalnej. 2018;72 (December): 1179–1198. doi.org/10.5604/01.3001.0012.8267.
11. Dominguez G, Condamine TC, Mony S, et al. Selective targeting of myeloid-derived suppressor cells in cancer patients using DS-8273a, an agonistic TRAIL-R2 antibody. Clin Cancer Res. 2017; (23) (12) 2942-2950. doi: 10.1158/1078-0432.CCR-16-1784.18.
12. Govallo VI. Immunology of Pregnancy and Cancer. Commack, N.Y: Nova Science Publishers; 1993:1-310. ISBN-10. 1560720964.
13. West RC, Bouma GJ, Winger QA. Shifting perspectives from “oncogenic” to oncofetal proteins; how these factors drive placental development. Reprod Biol Endocrinol. 2018;16, 101. doi.org/10.1186/s12958-018-0421-3.
14. Hammarstrom S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol. 1999; 9:67–81. doi: 10.1006/scbi.1998.0119.
15. Lee JH, Lee S-W. The Roles of Carcinoembryonic Antigen in Liver Metastasis and Therapeutic Approaches, Gastr.Res. Pract. 2017; vol. 2017, Article ID 7521987, 11 pages. doi.org/10.1155/2017/7521987.
16. Rayev MB, Zamorina SA, Litvinova LS, et al. The influence of chorionic gonadotropin on phenotype conversion and hTERT gene expression by T-lymphocytes of different degrees of differentiation. Biomed. Khim. 2017; 63 (6): 539–545. doi.org/10.18097/PBMC20176306539.
17. Zamorina SA, Timganova VP, Bochkova MS. The Role of Human Chorionic Gonadotropin and Its Peptide Fragments in the Regulation of IDO Expression by Human Monocytes. (Rus.). Rus. Immunol. J. 2018; 12(21) (3): 306–310. doi.org/10.31857/S102872210002400-5.
18. Gridelet V, d’Hauterive SP, Polese B, Foidart J.-M, Nisolle M, Geenen V. Human Chorionic Gonadotrophin: New Pleiotropic Functions for an ‘Old’ Hormone During Pregnancy. Front. Immunol. 2020; 11 (March): 343. doi.org/10.3389/fimmu.2020.00343.
19. Rayev MB, Litvinova LS, Yurova KA, et al. The Role of Pregnancy-Specific Glycoprotein in Regulation of Molecular Genetic Differentiation Mechanisms of Immune Memory T Cells. Med. Immunol. (Russia). 2019; 21 (1): 49–58. doi.org/10.15789/1563-0625-2019-1-49-58.
20. Timganova V, Bochkova M, Khramtsov P, Kochurova S, Rayev M, Zamorina S. Effects of Pregnancy-Specific β-1-Glycoprotein on the Helper T-Cell Response. Arch. Biol. Sci. 2019; 71 (2): 369–378. doi.org/10.2298/ABS190122019T.
21. Kui WN, Easton RL, Panico M, et al. Characterization of the oligosaccharides associated with the human ovarian tumor marker CA 125. J. Biol Chem. 2003; Aug 01;278(31):28619-28634. doi: 10.1074/jbc.M302741200.
22. Gandhi T, Bhatt H. Cancer Antigen 125. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022; Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562245.
23. Martini F, Guadagni F, Lenti L, et al. CA 19-9 monosialoganglioside content of human colorectal tumor cells correlates with tumor cell-induced platelet aggregation. Anticancer Res. 2000;20(3A):1609–16014. PMID: 10928079.
24. Chen Y, Wang YR, Deng GC, et al. CA19–9 decrease and survival according to platelet level in patients with advanced pancreatic cancer. BMC Cancer. 2019; 19, 860:1-8. doi.org/10.1186/s12885-019-6078-2.
25. Kennedy-Smith AG, McKenzie JL, Owen MC, Davidson PJ, Vuckovic S, Hart DN. Prostate specific antigen inhibits immune responses in vitro: a potential role in prostate cancer. J Urol. 2002; 168(2):741-747. PMID: 12131362
26. Westdorp H, Sköld AE, Snijer BA, et al. Immunotherapy for prostate cancer: lessons from responses to tumor-associated antigens. Front. Immunol. 2014;5:191:1-15. doi: 10.3389/fimmu.2014.00191.
27. Lakhi N, Moretti M, eds. Alpha-Fetoprotein: Functions and Clinical Application. Protein Biochemistry, Synthesis, Structure and Cellular Functions. Hauppauge, New York: Nova Science Publisher’s, Inc.; 2016: 1-420. ISBN: 978-1-63484-875-6.
28. Kirwan A, Utratna M, O’Dwyer ME, Joshi L, Kilcoyne M. Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics. BioMed Res. Int. 2015; 1–16. doi.org/10.1155/2015/490531.
29. Munson PV, Adamik J, Butterfield LH. Immunomodulatory impact of α-fetoprotein. Trends Immunol. 2022; Jun;43(6):438-448). doi: 10.1016/j.it.2022.04.001.
30. Nimmerjahn F, Ravetch JV. Fc-receptors as regulators of immunity. Adv Immunol. 2007;96:179-204. doi: 10.1016/S0065-2776(07)96005-8.
31. Pyzik M, Sand KMK, Hubbard JJ, Andersen JT, Sandlie I, Blumberg RS. The Neonatal Fc Receptor (FcRn): A Misnomer? Front. Immunol. 2019;10 (July): 1540. doi.org/10.3389/fimmu.2019.01540.
32. Blumberg RS, Pyzik M, Gandhi A, Sandlie I, Sand KMK, Andersen JT. Blockade of alphafetoprotein (AFP) interactions with beta2-microglobulin associated molecules. United States US20190201496A1, filed September 14, 2017, and issued July 4, 2019, https://patents.google.com/patent/US20190201496A1/en?oq=US+20190201496.
33. Hong H, Branham WS, Dial SL, et al. Rat α-Fetoprotein Binding Affinities of a Large Set of Structurally Diverse Chemicals Elucidated the Relationships between Structures and Binding Affinities. Chem. Res. Toxicol. 2012; 25 (11): 2553–2566. doi.org/10.1021/tx3003406.
34. Mizejewski GJ. A compendium of ligands reported to bind alpha-fetoprotein: a comprehensive review and metaanalysis. Canc. Ther. Oncol. Int. J. 2022; 20(5), 556047. DOI: 10.19080/CTOIJ.2022.20.556047.
35. Anel A, Calvo M, Naval J, Iturralde M, Alava MA, Piñeiro A. Interaction of Rat α-Fetoprotein and Albumin with Polyunsaturated and Other Fatty Acids: Determination of Apparent Association Constants. FEBS Letters. 1989;250 (1): 22–24. doi.org/10.1016/0014-5793(89)80676-3.
36. Hsia JC, Deutsch HF. An in Vitro Model of Placental Transfer of Polyunsaturated Fatty Acids: The Albumin-Alpha-Fetoprotein Exchange System. In Biological Activities of Alpha-Fetoprotein. 1987;1:205–211. USA: CRC Press, Inc.
37. Torres JM, Geuskens M, Uriel J. Receptor-Mediated Endocytosis and Recycling of Alpha-Fetoprotein in Human B-Lymphoma and T-Leukemia Cells. Int. J. Cancer. 1991;47 (1): 110–117. doi.org/10.1002/ijc.2910470120.
38. Pyzik M, Rath T, Lencer WI, Baker K, Blumberg RS. FcRn: The Architect Behind the Immune and Nonimmune Functions of IgG and Albumin. J. Immunol. (Baltimore, Md.: 1950). 2015; 194 (10): 4595–4603. doi.org/10.4049/jimmunol.1403014.
39. Vallette G, Vranckx R, Martin M.-E, Benassayag C, Nunez EA. Conformational Changes in Rodent and Human α-Fetoprotein: Influence of Fatty Acids. BBA – Prot. Struct. Mol. Enz. 1989;997 (3): 302–312. doi.org/10.1016/0167-4838(89)90201-X.
40. Uversky VN, Narizhneva NV. Effect of Natural Ligands on the Structural Properties and Conformational Stability of Proteins. (Rus.) Biochem. 1998;63 (4): 420–433. PMID: 9556525.
41. Uversky VN, Narizhneva NV, Ivanova TV, Tomashevski AYu. Rigidity of Human α-Fetoprotein Tertiary Structure Is under Ligand Control. Biochem. 1997;36 (44): 13638–13645. doi.org/10.1021/bi970332p.
42. Dudich IV, Semenkova LN, Tatulov E, Korpela T, Dudich E. Improved delivery of poorly water soluble drugs with alphafetoprotein stabilized with metal ions. World Intellectual Property Organization WO2015075296A1, filed November 18, 2014, and issued May 28, 2015. https://patents.google.com/patent/WO2015075296A1/en. 2015.
43. Permyakov SE, Oberg KA, Cherskaya AM, Shavlovsky MM, Permyakov EA, Uversky VN. Human α-Fetoprotein as a Zn2+-Binding Protein. Tight Cation Binding Is Not Accompanied by Global Changes in Protein Structure and Stability. BBA – Mol. Bas. Dis. 2002;1586 (1): 1–10. doi.org/10.1016/S0925-4439(01)00079-5.
44. Torres JM, Laborda J, Naval J, et al. Expression of Alpha-Fetoprotein Receptors by Human T-Lymphocytes during Blastic Transformation. Mol. Immunol. 1989;26 (9): 851–57.
doi.org/10.1016/0161-5890(89)90141-7.
45. Wang W, Alpert E. Downregulation of phorbol 12-myristate 13-acetate-induced tumor necrosis factor-α and interleukin-1β production and gene expression in human monocytic cells by human α-fetoprotein. Hepatol. 1995; 22: 921-928. PMID: 7544757.
46. Atemezem A, Mbemba E, Marfaing R, et al. Human AFP binds to primary macrophages. BBRC. 2002; 296: 507–514. doi.org/10.1016/S0006-291X(02)00909-9.
47. Esteban C, Geuskens M, Uriel J. Activation of an Alpha-Fetoprotein (AFP)/Receptor Autocrine Loop in HT-29 Human Colon Carcinoma Cells. Int. J. Cancer. 1991;49 (3): 425–430. doi.org/10.1002/ijc.2910490320.
48. Esteban C, Trojan J, Macho A, Mishal Z, Lafarge-Frayssinet C, Uriel J. Activation of an Alpha-Fetoprotein/Receptor Pathway in Human Normal and Malignant Peripheral Blood Mononuclear Cells. Leukemia. 1993;7 (11): 1807–16. PMID: 7544757.
49. Kanevsky VYu, Pozdnyakova LP, Aksenova OA, Severin SE, Katukov VYu, Severin ES. Isolation and characterization of AFP-binding proteins from tumor and fetal human tissues. Biochem Mol Biol Int. 1997; May;41(6):1143-1151. doi: 10.1080/15216549700202231.
50. Murgita, R, Goidl E, Kontianen S, Wigzellt H. α-Fetoprotein induces suppressor T cells in vitro. Nature. 1977;267, 257–259. doi.org/10.1038/267257a0.
51. Laan-Pütsep K, Wigzell H, Cotran P, Gidlund M. Human α-fetoprotein (AFP) causes a selective down regulation of monocyte MHC class II molecules without altering other induced or noninduced monocyte markers or functions in monocytoid cell lines. Cell. Immunol. 1991;133(2), 506–1810.
doi: 10.1016/0008-8749(91)90122-r.
52. Belyaev NN, Bogdanov AYu, Savvulidi PhG, et al. The influence of alpha-fetoprotein on natural suppressor cell activity and Ehrlich carcinoma growth. Korean J. Physiol. Pharmacol. 2008; (12):193-197. doi: 10.4196/kjpp.2008.12.4.193.
53. Zamorina SA, Shardina KY, Timganova VP, et al. Effect of Alpha-Fetoprotein on Differentiation of Myeloid Supressor Cells. Dokl Biochem Biophys. 2021; Nov;501(1):434-437. doi: 10.1134/S1607672921060077.
54. Suzuki Y, Zeng Q, Alpert E. Isolation and partial characterization of a specific α-fetoprotein receptor on human monocytes. J. Clin. Invest. 1992; 90:1530-1536. doi.org/10.1172/JCI116021.
55. Sedky HA, Youssef SR, Gamal DA, Houssein HF, Elsalakawy WA. First report of the unique expression of RECAF (receptor for alfa feto-protein) in adult B-NHL/CLL patients. Blood Res. 2020; Dec 31;55(4):253-261. doi: 10.5045/br.2020.2020070.
56. http://alpha-cancer.com/ceo-dr-igor-sherman-featured-in-ceocfo-magazine. Reached September 12, 2022.
57. Belyaev NN, Abdolla N, Perfilyeva YV, et al. Daunorubicin Conjugated with Alpha-Fetoprotein Selectively Eliminates Myeloid-Derived Suppressor Cells (MDSCs) and Inhibits Experimental Tumor Growth. Cancer Immunol. Immunother. 2018; CII 67 (1): 101–111. doi.org/10.1007/s00262-017-2067-y.
58. Severin SE, Kulakov VN, Moskaleva EY, Severin ES, Slobodianik II, Klimova TP. The distribution of iodine-125 labeled alpha-fetoprotein in the animal organism and its accumulation in the tumor. (Rus.) Vestnik RAMN. 2012; 4:11–15. PMID: 22834322.
59. Lin B, Dong X, Wang Q, Li W, Zhu M, Li M. AFP-Inhibiting fragments for drug delivery: the promise and challenges of targeting therapeutics to cancers. Front. Cell Dev. Biol. 2021;9, 635476. doi.org/10.3389/fcell.2021.635476.
60. Pak VN. The perfect combination of the most powerful cancer immunotherapy with the best targeted chemotherapy. Canc. Ther. Oncol. Int J. 2022; 20(5), 556050.
DOI: 10.19080/CTOIJ.2022.20.556050.61.
61. Sherman I, Boohaker R, Stinson K, Griffin P, Hill W. An alpha-fetoprotein-maytansine conjugate for the treatment of AFP receptor expressing tumors. J. Clin. Oncol. 40, no. 16_suppl (June 01, 2022) e15056-e15056. Doi: 10.1200/JCO.2022.40.16_suppl.e15056.
62. Terentiev AA, Moldogazieva NT, Levtsova OV, Maximenko DM, Borozdenko DA, Shaitan KV. Modeling of Three Dimensional Structure of Human Alpha-Fetoprotein Complexed with Diethylstilbestrol: Docking and Molecular Dynamics Simulation Study. J. Bioinf. Comput. Biol. 2012; 10 (2): 1241012. doi.org/10.1142/S0219720012410120.
63. TERIS webcite: http://depts.washington.edu/terisdb. Reached 2019.
64. Hirano K, Watanabe Y, Adachi T, Ito Y, Sugiura M. Drug binding properties of human alpha-fetoprotein. Biochem. J. 1985;231: 189–191. doi: 10.1042/bj2310189.
65. Mayer EL. An Oncologist’s Perspective on the Clinical Use of Teratogenic Products. Dana-Farber Cancer Institute, Boston, MA, USA. 2012; December 13. www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ DrugSafetyandRiskManagementAdvisoryCommittee/UCM333370.pdf. Reached 2012.
66. Bychkova VE, Ptitsyn OB. The molten globule in vitro and in vivo: Chemtracts. Biochem Mol Biol. 1993; 4:133–163.
67. Chereshnev VA, Rodionov SYu, Sherkasov VA, Malutina NN, Orlov ОА. Alpha-fetoprotein. (Rus.), Ekaterinburg, Ural Branch RAS. 2004:1-376 pages. ISBN 5-7691-1498-3.
68. Shardina KYu, Zamorina SA, Rayev MB, Cherechnev VA. The use of alpha-fetoprotein in immunopharmacology – history of the subject. Bulletin of Perm University. Biology. 2020;(2), 145–153. Doi: 10.17072/1994-9952-2020-2-145-153.
69. Gulevskyy OK, Akhatova YuS. Current Concept of the Structural and Functional Properties of Alpha-Fetoprotein and Possibilities of its Clinical Application. 2021; Biotech. Acta. 2021;14(1):25-37. doi.org/10.15407/biotech14.01.025.
70. Pollard LC, Murray J, Moody M, Stewart EJ, Choy EHS. A Randomised, Double-Blind, Placebo-Controlled Trial of a Recombinant Version of Human Alpha-Fetoprotein (MM-093) in Patients with Active Rheumatoid Arthritis. Ann. Rheum. Dis. 2007;66 (5): 687–89. doi.org/10.1136/ard.2006.059436.
71. ACT website: http://alpha-cancer.com Reached September 12, 2022.
72. Linson EA, Hanauer SB. More Than a Tumor Marker. A Potential Role for Alpha-Feto Protein in Inflammatory Bowel Disease. Inflam. Bowel Dis. 2019;25 (7): 1271–76. https://doi.org/10.1093/ibd/izy394.
73. Deutsch HF, Tsukada TS, Sasaki T, Hirai H. Cytotoxic Effects of Daunomycin-Fatty Acid Complexes on Rat Hepatoma Cells. Cancer Res. 198:43 (6): 2668–2672. PMID: 6850584.
74. Pak VN, Pak NA, Reshetnikov SS, Nikonov SD, Ogirenko AP. Method of treatment of malignant neoplasms and complex preparation having antineoplastic activity for use in such treatment. United States US6878688B2, filed June 20, 2001, issued April 12, 2005. https://patents.google.com/patent/US6878688B2/en.
75. Sotnichenko AI, Severin SE, Posypanova GA, et al. Water-Soluble 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Complex with Human Alpha-Fetoprotein: Properties, Toxicity in Vivo and Antitumor Activity in Vitro. FEBS Letters. 1999;450 (1–2): 49–51. doi.org/10.1016/s0014-5793(99)00440-8.
76. Arshad NM, In LLA, Soh TL, et al. Recombinant Human Alpha Fetoprotein Synergistically Potentiates the Anti-Cancer Effects of 1’-S-1’-Acetoxychavicol Acetate When Used as a Complex against Human Tumours Harbouring AFP-Receptors. Oncotarget. 2015;6 (18): 16151–16167. doi.org/10.18632/oncotarget.3951.
77. Kotra LP, Paige CJ, Bello AM, Sherman I. Drug complexes comprising alpha-fetoprotein. Patent WO/2016/119045A1. 2016. https://patentimages.storage.googleapis.com/0c/a7/ee/1fd56e9fbcb392/WO2016119045A1.pdf.
78. Dudich E, Semenkova L, Dudich I, Tatulov E. Method of reducing cancer cell proliferation by administering recombinant alpha-fetoprotein. United States Patent: 9931373, issued April 3, 2018. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2 Fsearch- adv.htm&r=1&f=G&l=50&d=PTXT&S1=9,931,373&OS=9,931,373&RS=9,931,373.
79. Pak VN. Alpha-fetoprotein and Its Receptor in Fixing the Cancer Brakes. Cambridge Scholars Publishing, Tyne, England; 2021:1-209. ISBN: 1-5275-6716-8.
80. AlphaFold Protein Structure Database webpage: https://alphafold.ebi.ac.uk/. Reached September 12, 2022.
81. Carlsson RN, Ingvarsson BI, Karlsson BW. Isolation and Characterization of Alpha-Foetoprotein from Foetal Pigs. Int. J. Biochem. 1976; 7: 13–20.
82. Pak VN. Compositions of alpha-fetoprotein and inducers of apoptosis for the treatment of cancer. European Patent EP1959978B1, issued December 30, 2015. https://patents.google.com/patent/EP1959978B1.
83. Pak VN, Molchanov O, Vincent M. Treatment of Metastatic Colorectal Cancer with Aimpila, a Glycoside/Alpha-Fetoprotein Complex. J. Clin. Oncol. 2007;25 (18_suppl): 3589–3589. doi.org/10.1200/jco.2007.25.18_suppl.3589.
84. Sevko A, Michels T, Vrohlings M, et al. Antitumor Effect of Paclitaxel Is Mediated by Inhibition of Myeloid-Derived Suppressor Cells and Chronic Inflammation in the Spontaneous Melanoma Model. J. Immunol. (Baltimore, Md.: 1950). 2013;190 (5): 2464–7241. https://doi.org/10.4049/jimmunol.1202781.
85. Sevko A, Umansky V. Myeloid-Derived Suppressor Cells Interact with Tumors in Terms of Myelopoiesis, Tumorigenesis and Immunosuppression: Thick as Thieves. J. Cancer. 2013;4 (1): 3–11. doi.org/10.7150/jca.5047.
86. Pak VN. The possible drug for cancer and metastasis prevention. Future Drug Discov. 2022;4(2). doi.org/10.4155/fdd-2022-0008.
87. Zhu X, Meng G, Dickinson BL, et al. MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. J. Immunol. 2001;166: 3266–3276. doi: 10.4049/jimmunol.166.5.3266.
88. Thomas J; Torok MA, Agrawal K, et al. The Neonatal Fc Receptor Is Elevated in Monocyte-Derived Immune Cells in Pancreatic Cancer. Int. J. Mol. Sci. 2022; 23, 7066. doi.org/10.3390/ijms23137066.
89. Um SH, Mulhall C, Alisa A, et al. Alpha-fetoprotein impairs APC function and induces their apoptosis. J Immunol. 2004;173(3):1772-1778. doi: 10.4049/jimmunol.173.3.1772.
90. Wildes TJ, DiVita Dean B, Flores CT. Myelopoiesis during Solid Cancers and Strategies for Immunotherapy. Cells. 2021;10(5):968. doi.org/10.3390/cells10050968.