PMID- 24284965 OWN - NLM STAT- MEDLINE DCOM- 20141015 LR - 20211021 IS - 1942-0870 (Electronic) IS - 1942-0862 (Print) IS - 1942-0862 (Linking) VI - 6 IP - 1 DP - 2014 Jan-Feb TI - Enhancement of anti-tumor CD8 immunity by IgG1-mediated targeting of Fc receptors. PG - 108-18 AB - Dendritic cells (DCs) function as professional antigen presenting cells and are critical for linking innate immune responses to the induction of adaptive immunity. Many current cancer DC vaccine strategies rely on differentiating DCs, feeding them tumor antigens ex vivo, and infusing them into patients. Importantly, this strategy relies on prior knowledge of suitable "tumor-specific" antigens to prime an effective anti-tumor response. DCs express a variety of receptors specific for the Fc region of immunoglobulins, and antigen uptake via Fc receptors is highly efficient and facilitates antigen presentation to T cells. Therefore, we hypothesized that expression of the mouse IgG1 Fc region on the surface of tumors would enhance tumor cell uptake by DCs and other myeloid cells and promote the induction of anti-tumor T cell responses. To test this, we engineered a murine lymphoma cell line expressing surface IgG1 Fc and discovered that such tumor cells were taken up rapidly by DCs, leading to enhanced cross-presentation of tumor-derived antigen to CD8+ T cells. IgG1-Fc tumors failed to grow in vivo and prophylactic vaccination of mice with IgG1-Fc tumors resulted in rejection of unmanipulated tumor cells. Furthermore, IgG1-Fc tumor cells were able to slow the growth of an unmanipulated primary tumor when used as a therapeutic tumor vaccine. Our data demonstrate that engagement of Fc receptors by tumors expressing the Fc region of IgG1 is a viable strategy to induce efficient and protective anti-tumor CD8+ T cell responses without prior knowledge of tumor-specific antigens. FAU - Furlan, Scott N AU - Furlan SN FAU - Mandraju, Rajakumar AU - Mandraju R FAU - Brewer, Travis AU - Brewer T FAU - Roybal, Kole AU - Roybal K FAU - Troutman, Ty Dale AU - Troutman TD FAU - Hu, Wei AU - Hu W FAU - Palm, Noah W AU - Palm NW FAU - Unni, Arun AU - Unni A FAU - Pasare, Chandrashekhar AU - Pasare C LA - eng GR - T32 AI005284/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - MAbs JT - mAbs JID - 101479829 RN - 0 (Immunoglobulin G) RN - 0 (Neoplasm Proteins) RN - 0 (Receptors, Fc) SB - IM MH - Animals MH - CD8-Positive T-Lymphocytes/*immunology/metabolism/pathology MH - Cell Line, Tumor MH - *Immunity, Cellular MH - Immunoglobulin G/*immunology/metabolism MH - Lymphoma/*immunology/metabolism/therapy MH - Mice MH - Neoplasm Proteins/biosynthesis/*immunology MH - Receptors, Fc/biosynthesis/*immunology PMC - PMC3929435 EDAT- 2013/11/29 06:00 MHDA- 2014/10/16 06:00 PMCR- 2015/01/01 CRDT- 2013/11/29 06:00 PHST- 2013/11/29 06:00 [entrez] PHST- 2013/11/29 06:00 [pubmed] PHST- 2014/10/16 06:00 [medline] PHST- 2015/01/01 00:00 [pmc-release] AID - 27052 [pii] AID - 2013MABS0420R [pii] AID - 10.4161/mabs.27052 [doi] PST - ppublish SO - MAbs. 2014 Jan-Feb;6(1):108-18. doi: 10.4161/mabs.27052.