Page 320 - 2014 Printable Abstract Book
P. 320
2°, 4 non-European variant, of which 3 had the Asian American variant (AA), 2 AA subclass subclass a, 1 C,
and one (Nd). Of these 34 patients, 15 received complete radiotherapy (8 complete responders (3 E-T350,
2 E-nd, 2 E-G350, 1 AAa, 4 with partial response (2 E-350T; 2 E-350G), 3 with tumor persistence (2 E-G350;
1 E-nd)), 2 incomplete radiotherapy (1 E-T350, 1 G350), 4 discontinued treatment (1 AAC, 1 E-nd, 2 E-
G350), 4 received radiochemotherapy (2 E-nd, 1 E-G350, 1 E-T350) and 8 did not receive treatment (4 E-
T350 , 4 E-G350). Although an association between the presence of variants and response to radiotherapy
in patients treated do not find, it is important to note the high frequency of European variants at
treatment, specifically the presence of the European variant R10G, due to that in the recent functional
tests was reported that this variation significantly shortens the lifespan of p53 as compared with other
variants of E6, hindering the role p53 in apoptosis after irradiation.
(PS5-57) Characterization and targeting of TAF15, a radiation-inducible target in multiple cancer types.
Lincoln Muhoro; Heping Yan, MD; Jeremy Hunn; Daniel Ferraro; Jerry Jaboin; and Dennis Hallahan
Washington University in St. Louis School of Medicine, Saint Louis, MO
Currently, development of anti-cancer therapies is limited to antigens that are either
overexpressed or that are specific to cancer. This limits both the number of available targets and their
tumor selectivity. We have identified a number of proteins in multiple cancers that are induced by sub-
lethal doses of ionizing radiation (IR), including TATA-box-binding protein associated factor 15 (TAF-15), a
key transcriptional regulator. TAF15 presents a novel synergistic molecular target for the treatment of
cancer using IR. In this study, we characterized TAF15 as a radiation-inducible molecular target both in
vitro and in vivo using various analytical approaches. Using Western blot and qPCR analysis, we screened
multiple cancer cell lines including glioma, lung, breast and pancreatic panels and showed that TAF15 is
overexpressed in multiple cancer cells relative to normal cells. More importantly, we found that TAF15
expression is further enhanced with IR treatment. Near-infra red imaging showed targeting to TAF15 in
several irradiated human tumor xenografts in nude mice using both an anti-TAF15 peptide and anti-TAF15
antibody. We also performed an IR dose-dependent and IR time-lapse study in breast cancer. Results
showed that TAF15 is optimally induced at a dose of 6Gy and within 1hr post-IR, suggesting that it may
act as an early-response gene in cancer cells exposed to IR stress. Surface expression analysis of TAF15 via
flow cytometry showed that TAF15 is expressed on the surface of cancer. We are currently evaluating its
potential as a therapeutic and imaging target. Using hybridoma technology, we have selected new
monoclonal antibodies against 3 different TAF15 epitopes. We are also currently testing the in vivo
efficacy of an in-house targeted TAF15 peptide using radioisotope labeling for both imaging and
therapeutic purposes. We will then evaluate the distribution of TAF15 in the tumor microenvironment
and assess the specificity and efficacy of our lead anti-TAF15 antibody.
(PS5-58) Influence of subcellular localization and microenvironment on radiosensitization of cancer cells
by conjugated gold nanoparticles. Pankaj K. Singh; Parmeswaran Diagaradjane, PhD; Tatiana Wolfe, PhD;
JiHyoun Lee, MD; Ramesh C. Tailor, PhD; and Sunil Krishnan, MD; Anderson Cancer Center, Houston, TX
Purpose: To evaluate the influence of subcellular localization and microenvironment of
internalized cetuximab-conjugated gold nanorods (cGNRs) on radiosensitization of head and neck cancer
cells. Methods: Pharmacologic inhibitors were used to block different steps of nanoparticle internalization
318 | P a g e
and one (Nd). Of these 34 patients, 15 received complete radiotherapy (8 complete responders (3 E-T350,
2 E-nd, 2 E-G350, 1 AAa, 4 with partial response (2 E-350T; 2 E-350G), 3 with tumor persistence (2 E-G350;
1 E-nd)), 2 incomplete radiotherapy (1 E-T350, 1 G350), 4 discontinued treatment (1 AAC, 1 E-nd, 2 E-
G350), 4 received radiochemotherapy (2 E-nd, 1 E-G350, 1 E-T350) and 8 did not receive treatment (4 E-
T350 , 4 E-G350). Although an association between the presence of variants and response to radiotherapy
in patients treated do not find, it is important to note the high frequency of European variants at
treatment, specifically the presence of the European variant R10G, due to that in the recent functional
tests was reported that this variation significantly shortens the lifespan of p53 as compared with other
variants of E6, hindering the role p53 in apoptosis after irradiation.
(PS5-57) Characterization and targeting of TAF15, a radiation-inducible target in multiple cancer types.
Lincoln Muhoro; Heping Yan, MD; Jeremy Hunn; Daniel Ferraro; Jerry Jaboin; and Dennis Hallahan
Washington University in St. Louis School of Medicine, Saint Louis, MO
Currently, development of anti-cancer therapies is limited to antigens that are either
overexpressed or that are specific to cancer. This limits both the number of available targets and their
tumor selectivity. We have identified a number of proteins in multiple cancers that are induced by sub-
lethal doses of ionizing radiation (IR), including TATA-box-binding protein associated factor 15 (TAF-15), a
key transcriptional regulator. TAF15 presents a novel synergistic molecular target for the treatment of
cancer using IR. In this study, we characterized TAF15 as a radiation-inducible molecular target both in
vitro and in vivo using various analytical approaches. Using Western blot and qPCR analysis, we screened
multiple cancer cell lines including glioma, lung, breast and pancreatic panels and showed that TAF15 is
overexpressed in multiple cancer cells relative to normal cells. More importantly, we found that TAF15
expression is further enhanced with IR treatment. Near-infra red imaging showed targeting to TAF15 in
several irradiated human tumor xenografts in nude mice using both an anti-TAF15 peptide and anti-TAF15
antibody. We also performed an IR dose-dependent and IR time-lapse study in breast cancer. Results
showed that TAF15 is optimally induced at a dose of 6Gy and within 1hr post-IR, suggesting that it may
act as an early-response gene in cancer cells exposed to IR stress. Surface expression analysis of TAF15 via
flow cytometry showed that TAF15 is expressed on the surface of cancer. We are currently evaluating its
potential as a therapeutic and imaging target. Using hybridoma technology, we have selected new
monoclonal antibodies against 3 different TAF15 epitopes. We are also currently testing the in vivo
efficacy of an in-house targeted TAF15 peptide using radioisotope labeling for both imaging and
therapeutic purposes. We will then evaluate the distribution of TAF15 in the tumor microenvironment
and assess the specificity and efficacy of our lead anti-TAF15 antibody.
(PS5-58) Influence of subcellular localization and microenvironment on radiosensitization of cancer cells
by conjugated gold nanoparticles. Pankaj K. Singh; Parmeswaran Diagaradjane, PhD; Tatiana Wolfe, PhD;
JiHyoun Lee, MD; Ramesh C. Tailor, PhD; and Sunil Krishnan, MD; Anderson Cancer Center, Houston, TX
Purpose: To evaluate the influence of subcellular localization and microenvironment of
internalized cetuximab-conjugated gold nanorods (cGNRs) on radiosensitization of head and neck cancer
cells. Methods: Pharmacologic inhibitors were used to block different steps of nanoparticle internalization
318 | P a g e
