Depletion of regulatory T cells by targeting folate receptor 4 enhances the potency of a GM-CSF-secreting tumor cell immunotherapy
Copyright © 2013 Elsevier Inc. All rights reserved.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 148(2013), 2 vom: 15. Aug., Seite 287-98 |
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| Weitere Verfasser: | , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2013
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Cancer immunotherapy Costimulation T cells Tregs Antibodies Cancer Vaccines Receptors, Cell Surface folate receptor 4, mouse Granulocyte-Macrophage Colony-Stimulating Factor |
| Zusammenfassung: | Copyright © 2013 Elsevier Inc. All rights reserved. In this report, a Treg-depleting anti-FR4 antibody is combined with a GM-CSF-secreting tumor cell immunotherapy (GVAX) for treatment of melanoma-bearing animals. Median survival time (MST) of animals treated with GVAX was 41 days, compared to a MST of 32 days in untreated animals. Anti-FR4 monotherapy had no effect on MST. Combination of anti-FR4 and GVAX significantly prolonged MST to 55 days, suggesting that these two agents can function cooperatively. Combination therapy increased expression of IFN-γ and granzyme B by CD8 T cells. In contrast to anti-CD25-mediated Treg depletion, administration of anti-FR4 after GVAX did not reduce efficacy, suggesting that anti-FR4 does not deplete effector cells induced by GVAX. Triple combination of a blocking CTLA4 antibody with GVAX and anti-FR4 further enhanced overall survival and reduced growth of well-established melanomas. Considered together, anti-FR4 antibody and GVAX may be a promising approach for the treatment of patients with cancer |
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| Beschreibung: | Date Completed 17.09.2013 Date Revised 08.04.2022 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2013.05.011 |