Abstract 5620: Novel phage display-derived neuroblastoma-targeting peptides potentiate the effect of drug nanocarriers in preclinical settings.
Bibliographic record
Abstract
Abstract Purpose: Molecular targeting of drug delivery nanocarriers is expected to improve their therapeutic index while decreasing their toxicity. The identification of novel peptide ligands specific for cells present in high-risk neuroblastoma, a childhood tumor mostly refractory to current therapies, is needed. Experimental design: We performed combined in vitro/ex-vivo phage display screenings on human neuroblastoma cell lines and on tumors derived from orthotopic mouse models of human neuroblastoma. Binding validation and homing in vivo of selected phage clones were tested by immunohistochemistry/immunofluorescent analyses. Cell association experiments in vitro with the corresponding synthetic biotin-labeled peptides were performed. In vitro cytotoxicity and in vivo tumor accumulation and therapeutic experiments were performed using peptide-targeted, doxorubicin-loaded, nanocarriers. Results: By designing proper subtractive protocols, we identified phage clones specific either for the primary tumor, its metastases, or for the stromal components. Globally, we isolated 121 phage-displayed neuroblastoma-binding peptides; of these, 26 bound the primary tumor, 15 the metastatic mass, 57 and 23 their respective microenvironments. Of these, five phage clones were further validated for their specific binding ex-vivo to biopsies from stage IV neuroblastoma patients and to neuroblastoma tumors derived from mice. All five clones also targeted tumor cells and vasculature in vivo when injected into neuroblastoma-bearing mice. Coupling of the corresponding targeting peptides with doxorubicin-loaded nanocarriers led to a significant inhibition in tumor volume and enhanced survival in preclinical neuroblastoma models. Conclusions: Our findings demonstrate that novel ligands of neuroblastoma-associated markers are functional in the design of nanocarriers with therapeutic efficacy paving the way to their clinical development. Citation Format: Monica Loi, Daniela Di Paolo, Marco Soster, Chiara Brignole, Alice Bartolini, Laura Emionite, Jessica Sun, Pamela Becherini, Flavio Curnis, Andrea Petretto, Monica Sani, Alessandro Gori, Claudio Gambini, Renato Longhi, Michele Cilli, Theresa M. Allen, Federico Bussolino, Wadih Arap, Renata Pasqualini, Angelo Corti, Mirco Ponzoni, Serena Marchiò, Fabio Pastorino. Novel phage display-derived neuroblastoma-targeting peptides potentiate the effect of drug nanocarriers in preclinical settings. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5620. doi:10.1158/1538-7445.AM2013-5620
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".