Induction of potent NK cell-dependent anti-myeloma cytotoxic T cells in response to combined mapatumumab and bortezomib
Paul J Neeson, Andy K Hsu, Yin R Chen, Heloise M Halse, Joanna Loh, Reece Cordy, Kate Fielding, Joanne Davis, Josh Noske, Alex J Davenport, Camilla A Lindqvist-Gigg, Robin Humphreys, Tsin Tai, H Miles Prince, Joseph A Trapani, Mark J Smyth, David S Ritchie
OncoImmunology | TAYLOR & FRANCIS INC | Published : 2015
There is increasing evidence that some cancer therapies can promote tumor immunogenicity to boost the endogenous antitumor immune response. In this study, we used the novel combination of agonistic anti-TRAIL-R1 antibody (mapatumumab, Mapa) with low dose bortezomib (LDB) for this purpose. The combination induced profound myeloma cell apoptosis, greatly enhanced the uptake of myeloma cell apoptotic bodies by dendritic cell (DC) and induced anti-myeloma cytotoxicity by both CD8+ T cells and NK cells. Cytotoxic lymphocyte expansion was detected within 24 h of commencing therapy and was maximized when myeloma-pulsed DC were co-treated with low dose bortezomib and mapatumumab (LDB+Mapa) in the pr..View full abstract
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Awarded by National Health and Medical Research Council of Australia
This work was completed with funding from Human Genome Sciences Inc. and National Health and Medical Research Council of Australia (program grants 454569 and 1013667).