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.