The Role of Complement in Cancer Immunotherapy
The dual role of complement in both cancer development and treatment has been investigated extensively and is characterized by a substantial literature that documents the conditions in which complement can either enhance tumor growth or promote the killing of malignant cells. Indeed, there are now n...
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MDPI - Multidisciplinary Digital Publishing Institute
2022
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| Linkit: | ONIX_20220224_9783036529394_126 |
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| description | The dual role of complement in both cancer development and treatment has been investigated extensively and is characterized by a substantial literature that documents the conditions in which complement can either enhance tumor growth or promote the killing of malignant cells. Indeed, there are now numerous examples of monoclonal antibodies (mAbs) that have either been approved by the FDA or that are under active investigation that make use of complement when eliminating cancer cells. Although the direct in vitro killing of mAb-opsonized cancer cell lines by complement-dependent cytotoxicity (CDC) can be readily demonstrated, there are considerable challenges related to the translation of these findings to the clinic, and numerous strategies have been employed to maximize mAb-mediated CDC in cancer treatment. These approaches include the redesign of mAb dosing schedules; engineering the Fc regions of the mAbs to enhance complement activation; treatment with cocktails of mAbs that bind to several different sites on the targeted cells and thus that potentially synergize CDC promotion; and neutralizing the complement control proteins on malignant cells to weaken their defenses against complement. Target sites on malignant cells that have been successfully exploited for mAb-induced CDC include CD20, CD37, CD38, CD52, and Epidermal Growth Factor Receptors. MAbs specific to complement components have served as powerful analytical reagents to investigate the detailed mechanisms of CDC, and they have been employed to document complement activation by cancer cells and to examine the role of complement proteins (in particular C1q and fragments of C3 and C5) in supporting tumor growth. The use of polyclonal and mAb reagents has revealed a role for the intracellular complement system in cancer biology and strategies that focus on the interaction of complement with the tumor microenvironment, and examining the impact of the complotype on the response to immunotherapy in cancer should lead to additional mAb-based therapies. Along these lines, there is now increasing evidence that strategies that make use of mAbs or other agents to modulate the action of C3a/C5a or their respective receptors may also find use in cancer immunotherapy. |
| format | Online |
| id | doab-20.500.12854ir-78828 |
| institution | Directory of Open Access Books |
| language | eng |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | MDPI - Multidisciplinary Digital Publishing Institute |
| publisherStr | MDPI - Multidisciplinary Digital Publishing Institute |
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| spelling | doab-20.500.12854ir-788282024-03-30T23:21:56Z The Role of Complement in Cancer Immunotherapy Taylor, Ronald P. complement therapeutic monoclonal antibodies (mAbs) Ca2+ fluorescence microscopy gC1qR breast cancer xenotransplant model complement system cancer immune infiltrate tumor microenvironment tumor growth anaphylatoxins antibody dependent cellular cytotoxicity phagocytosis complement receptors CD46 membrane cofactor protein (MCP) cancer therapeutics measles virus adenovirus antibody-drug conjugates immunity myeloid cells therapeutics antibody therapy cluster of differentiation 19 (CD19) CD19 Fc fragment crystallizable (Fc) Fc engineering complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC) angiogenesis ocular pathology cytotoxicity monoclonal antibody B-cell lymphoma chronic lymphocytic leukemia (CLL) complement C5a complement C3a mammary carcinoma immunoregulation tumor infiltrating leukocytes n/a thema EDItEUR::M Medicine and Nursing The dual role of complement in both cancer development and treatment has been investigated extensively and is characterized by a substantial literature that documents the conditions in which complement can either enhance tumor growth or promote the killing of malignant cells. Indeed, there are now numerous examples of monoclonal antibodies (mAbs) that have either been approved by the FDA or that are under active investigation that make use of complement when eliminating cancer cells. Although the direct in vitro killing of mAb-opsonized cancer cell lines by complement-dependent cytotoxicity (CDC) can be readily demonstrated, there are considerable challenges related to the translation of these findings to the clinic, and numerous strategies have been employed to maximize mAb-mediated CDC in cancer treatment. These approaches include the redesign of mAb dosing schedules; engineering the Fc regions of the mAbs to enhance complement activation; treatment with cocktails of mAbs that bind to several different sites on the targeted cells and thus that potentially synergize CDC promotion; and neutralizing the complement control proteins on malignant cells to weaken their defenses against complement. Target sites on malignant cells that have been successfully exploited for mAb-induced CDC include CD20, CD37, CD38, CD52, and Epidermal Growth Factor Receptors. MAbs specific to complement components have served as powerful analytical reagents to investigate the detailed mechanisms of CDC, and they have been employed to document complement activation by cancer cells and to examine the role of complement proteins (in particular C1q and fragments of C3 and C5) in supporting tumor growth. The use of polyclonal and mAb reagents has revealed a role for the intracellular complement system in cancer biology and strategies that focus on the interaction of complement with the tumor microenvironment, and examining the impact of the complotype on the response to immunotherapy in cancer should lead to additional mAb-based therapies. Along these lines, there is now increasing evidence that strategies that make use of mAbs or other agents to modulate the action of C3a/C5a or their respective receptors may also find use in cancer immunotherapy. 2022-02-24T10:37:55Z 2022-02-24T10:37:55Z 2022 book ONIX_20220224_9783036529394_126 9783036529394 9783036529387 https://directory.doabooks.org/handle/20.500.12854/78828 eng image/jpeg Attribution 4.0 International https://mdpi.com/books/pdfview/book/4923 https://mdpi.com/books/pdfview/book/4923 MDPI - Multidisciplinary Digital Publishing Institute 10.3390/books978-3-0365-2939-4 10.3390/books978-3-0365-2939-4 46cabcaa-dd94-4bfe-87b4-55023c1b36d0 9783036529394 9783036529387 184 Basel open access |
| spellingShingle | complement therapeutic monoclonal antibodies (mAbs) Ca2+ fluorescence microscopy gC1qR breast cancer xenotransplant model complement system cancer immune infiltrate tumor microenvironment tumor growth anaphylatoxins antibody dependent cellular cytotoxicity phagocytosis complement receptors CD46 membrane cofactor protein (MCP) cancer therapeutics measles virus adenovirus antibody-drug conjugates immunity myeloid cells therapeutics antibody therapy cluster of differentiation 19 (CD19) CD19 Fc fragment crystallizable (Fc) Fc engineering complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC) angiogenesis ocular pathology cytotoxicity monoclonal antibody B-cell lymphoma chronic lymphocytic leukemia (CLL) complement C5a complement C3a mammary carcinoma immunoregulation tumor infiltrating leukocytes n/a thema EDItEUR::M Medicine and Nursing The Role of Complement in Cancer Immunotherapy |
| title | The Role of Complement in Cancer Immunotherapy |
| title_full | The Role of Complement in Cancer Immunotherapy |
| title_fullStr | The Role of Complement in Cancer Immunotherapy |
| title_full_unstemmed | The Role of Complement in Cancer Immunotherapy |
| title_short | The Role of Complement in Cancer Immunotherapy |
| title_sort | role of complement in cancer immunotherapy |
| topic | complement therapeutic monoclonal antibodies (mAbs) Ca2+ fluorescence microscopy gC1qR breast cancer xenotransplant model complement system cancer immune infiltrate tumor microenvironment tumor growth anaphylatoxins antibody dependent cellular cytotoxicity phagocytosis complement receptors CD46 membrane cofactor protein (MCP) cancer therapeutics measles virus adenovirus antibody-drug conjugates immunity myeloid cells therapeutics antibody therapy cluster of differentiation 19 (CD19) CD19 Fc fragment crystallizable (Fc) Fc engineering complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC) angiogenesis ocular pathology cytotoxicity monoclonal antibody B-cell lymphoma chronic lymphocytic leukemia (CLL) complement C5a complement C3a mammary carcinoma immunoregulation tumor infiltrating leukocytes n/a thema EDItEUR::M Medicine and Nursing |
| topic_facet | complement therapeutic monoclonal antibodies (mAbs) Ca2+ fluorescence microscopy gC1qR breast cancer xenotransplant model complement system cancer immune infiltrate tumor microenvironment tumor growth anaphylatoxins antibody dependent cellular cytotoxicity phagocytosis complement receptors CD46 membrane cofactor protein (MCP) cancer therapeutics measles virus adenovirus antibody-drug conjugates immunity myeloid cells therapeutics antibody therapy cluster of differentiation 19 (CD19) CD19 Fc fragment crystallizable (Fc) Fc engineering complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC) angiogenesis ocular pathology cytotoxicity monoclonal antibody B-cell lymphoma chronic lymphocytic leukemia (CLL) complement C5a complement C3a mammary carcinoma immunoregulation tumor infiltrating leukocytes n/a thema EDItEUR::M Medicine and Nursing |
| url | ONIX_20220224_9783036529394_126 |