David M. Spencer, Ph.D.
Immunology
Enhanced Dendritic Cell-based Immunotherapy for Cancer
Dr. Spencer received the award for his work on developing a novel immune therapy-based
approach to treating cancer, which relies on a small-molecule dimerizer to improve
dendritic cell (DC) function. In one iteration, they used the chemically induced
dimerization (CID) technology he co-invented years earlier to manipulate the costimulatory
CD40 molecule in DCs, leading to a much more potent vaccine against poorly immunogenic
self-peptides. In a complementary approach, his group developed a novel potent constitutive
Akt allele and applied this technology to extending the lifespan and potency of
DCs in several vaccine models. After demonstrating equally impressive potency in
human DCs, Dr. Spencer initiated collaborations with colleagues on related clinical
studies.
Dr. Spencer also developed a series of state-of-the-art non-immunogenic suicide
genes for gene therapy, which utilize endogenous caspase family proteases and CID
technology. These inducible caspases are likely to become increasingly important
as a safety switch for retrovirus-based gene therapy and are the basis of upcoming
clinical studies. The Spencer lab has used these conditional pro-apoptotic molecules
as part of a potent, novel neoadjuvant therapy for prostate cancer.
Dr. Spencer's nomination was based on the following publications:
Hanks BA, Jiang J, Singh RA, Song W, Barry M, Huls MH, Slawin KM, Spencer DM. "
Re-engineered CD40 receptor enables potent pharmacological activation of dendritic-cell
cancer vaccines in vivo. ". Nat Med. 2005 Feb;11(2):130-7.
Nikitina EY, Desai SA, Zhao X, Song W, Luo AZ, Gangula RD, Slawin KM, Spencer DM.
"
Versatile prostate cancer treatment with inducible caspase and interleukin-12.
". Cancer Res. 2005 May 15;65(10):4309-19.
Park D, Lapteva N, Seethammagari M, Slawin KM, Spencer DM."
. An essential role for Akt1 in dendritic cell function and tumor immunotherapy.
Nat Biotechnol. ". 2006 Dec;24(12):1581-90.
Lapteva N, Seethammagari MR, Hanks BA, Jiang J, Levitt JM, Slawin KM, Spencer DM.
Enhanced activation of human dendritic cells by inducible CD40 and Toll-like receptor-4
ligation. ". Cancer Res. 2007 Nov 1;67(21):10528-37.