Figure 1.
Consort style flowchart of participants through the study.
Table 1.
Baseline Characteristics of Patients.
Table 2.
Dose-Escalation Scheme, Toxicities, and Tumor Response.
Figure 2.
DC-TUSC2 metabolic tumor response in a metastatic lung cancer patient.
The patient is a 54 year old female with a large cell neuroendocrine carcinoma. She had received six prior chemotherapy regimens. Prior to entry in the protocol, two hepatic metastases were progressing on gemcitabine. The patient also had a metastasis in the head of the pancreas and a peripancreatic lymph node (arrows). A. Pretreatment PET scan. The dose of Fluorodeoxyglucose(18F) was 8.8mCi B. Post-treatment PET scan performed 20 days following the fourth dose of DC-TUSC2. The dose of Fluorodeoxyglucose(18F) was 9.0mCi. All scans were performed within a 60 to 90 minute window after injection.
Figure 3.
In situ Proximity Ligation Assay (PLA) for TUSC2 protein in tumor biopsies (A).
A synthetic oligopeptide (GASGSKARGLWPFASAA) derived from the N-terminal amino-acid sequence of the TUSC2 protein was used to develop the anti-TUSC2 polyclonal antibody in rabbits used in this study. Red denotes TUSC2 positivity. DAPI nuclear staining is blue. All panels represent overlays of TUSC2 antibody and DAPI staining. Detailed methods are provided in the Information S1. Pre- and post-treatment biopsies from patients 13, 26, and 31 were tested. Magnification is X40. Panels: (1) anti-TUSC2 antibody; (2) anti-TUSC2 antibody pre-absorbed with non-specific control peptide (NSP); (3) anti-TUSC2 antibody pre-absorbed with TUSC2 peptide (FP); (4) non-specific control antibody; (5) hematoxylin and eosin. Quantitation of PLA signals for pre- and post-treatment samples from patients 13, 26, and 31 (B). The anti-TUSC2 antibody was tested under the conditions described in A). The upper panels show PLA signals from the respective patient biopsies as detected by the anti-TUSC2 antibody with 400× magnification. The lower panel presents quantitative comparisons of six independent fields from each biopsy treated under the specified conditions. TUSC2 expression was significantly increased in post-treatment samples compared to pretreatment samples. TUSC2 expression was not significantly altered by anti-TUSC2 antibody pre-absorption with non-specific control peptide (NSP), but was significantly decreased by pre-absorption with TUSC2 peptide (FP). * p<0.05 compared to corresponding pretreatment sample; ▪ p<0.05 compared to post-treatment samples unabsorbed or pre-absorbed with NSP. All comparisons are by two-tailed unpaired Student's t-test assuming equal variances as determined by F test.
Table 3.
Real Time RT-PCR detection of TUSC2 gene expression in patients receiving DC-TUSC2.