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Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2.
- Source :
-
Cancer cell [Cancer Cell] 2015 Apr 13; Vol. 27 (4), pp. 489-501. - Publication Year :
- 2015
-
Abstract
- Cancer immunotherapies under development have generally focused on either stimulating T cell immunity or driving antibody-directed effector functions of the innate immune system such as antibody-dependent cell-mediated cytotoxicity (ADCC). We find that a combination of an anti-tumor antigen antibody and an untargeted IL-2 fusion protein with delayed systemic clearance induces significant tumor control in aggressive isogenic tumor models via a concerted innate and adaptive response involving neutrophils, NK cells, macrophages, and CD8(+) T cells. This combination therapy induces an intratumoral "cytokine storm" and extensive lymphocyte infiltration. Adoptive transfer of anti-tumor T cells together with this combination therapy leads to robust cures of established tumors and development of immunological memory.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Adaptive Immunity
Animals
CD8-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes immunology
Drug Synergism
Half-Life
Immunity, Innate
Immunotherapy
Interleukin-2 metabolism
Interleukin-2 pharmacokinetics
Interleukin-2 pharmacology
Killer Cells, Natural drug effects
Killer Cells, Natural immunology
Mice
Mice, Inbred C57BL
Neoplasms immunology
Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3686
- Volume :
- 27
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer cell
- Publication Type :
- Academic Journal
- Accession number :
- 25873172
- Full Text :
- https://doi.org/10.1016/j.ccell.2015.03.004