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In vivo synergy of radiation and hu14.18-IL2 immunocytokine results in a memory T cell response in a syngeneic murine melanoma model
© Morris et al.; licensee BioMed Central Ltd. 2014
Published: 6 November 2014
Tumor-specific monoclonal antibodies (mAb) are a common type of immunotherapy capable of engaging innate immune cells to elicit antibody-dependent cell-mediated cytotoxicity (ADCC). We recently demonstrated in vivo synergy between radiation (RT) and ADCC using the anti-GD2 hu14.18 mAb. We now investigate the potential of hu14.18-IL2 immunocytokine (IC) to augment this synergy.
Method and materials
C57BL/6 mice were engrafted with syngeneic GD2-expressing B78 melanoma. Macroscopic tumors (~ 200 mm3) were treated with sham or single fraction 12 Gy RT. Mice then received 5 daily intra-tumor injections of human IgG, hu14.18 mAb, or hu14.18-IL2 IC. NK or T cell depletion was achieved by intraperitoneal injection of a depleting mAb (NK1.1 or CD4/CD8 mAbs). After 90 days mice rendered disease-free by initial treatment were re-challenged with a second injection of B78 melanoma. After an additional 30 days mice not developing tumors were injected at distinct sites with syngeneic B16 melanoma (related to B78 but lacking GD2) and Panc02 pancreatic cancer cells.
We present evidence of synergy between RT and hu14.18-IL2 resulting in a memory T cell response. Our findings suggest a therapeutic opportunity for combining RT with immunotherapies that simultaneously target innate immune response and T-cell activation.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.