Abstract LB221: Novel molecular targeted tumor targeted oncolytic peptide for the treatment of therapy resistant progressive neuroblastoma

Abstract Cancer treatments, particularly for solid tumors like neuroblastoma, often entail severe side effects, resistance, and the potential for secondary malignancies. To address these challenges, we explored an innovative approach employing tumor-targeting peptides. Recently, we unveiled the tumor evolution regulatory role of retinal-degeneration protein-3 (RD3) in therapy defying progressive tumors. Here in we investigated the therapeutic potential of RD3 peptides. Utilizing neuroblastoma, the most common cancer at infancy, as the tumor model, we investigated the delivery and therapeutic potential RD3 peptide. Five peptides representing unique regions, each with a C-terminal TAT tag for fluorescence and an N-terminal amide cap were developed. Peptide homing capabilities (Cell Tracking aasay) and relative potential in modifying metastatic state including invasion (Matrigel invasion assay), migration (scratch-wound assay), clonal expansion (LDTA) and tumorosphere formation (LDTA) was investigated utilizing patient derived clinical therapy defied progressive NB cells NB-EBc1 from adrenal mass and SK-N-FI from bone marrow. Whole genome RNA sequencing was performed using novogene (Illumina) platform. All peptides screened displayed tumor cell internalization and inflicted cell death at varying degrees. Among the five peptides investigated, two peptides (RD3 Pep-1 and RD3 Pep-3) profoundly inhibited cell proliferation, migration, invasion, and tumorosphere formation. A novel molecular targeted oncolytic peptide, validated through RNA sequencing, demonstrates promising efficacy for treating therapy-resistant progressive neuroblastoma. These outcomes uniquely highlight the therapeutic potential of RD3 peptides, offering a novel therapeutic candidate to counter therapy defying progressive disease. Further, the results defined the synergistic benefit RD3 peptide deliver with the current clinical maintenance therapy (GD2 immunotherapy for neuroblastoma). Together, these results identified a molecular targeted novel oncolytic peptide that could complement current standards of maintenance therapy for therapy defying progressive disease. Funding: This work was partially or in full, funded by Oklahoma Center for the Advancement of Science and Technology, OCAST-HR19-04; National Institutes of Health, NIH-P20GM103639 and; NIH-NCI- Cancer Center Support Grant P30CA225520 and Department of Defense DoD-CA210339. Citation Format: Dinesh Babu Somasundaram, Poorvi Subramanian, Sreenidhi Mohanvelu, Sheeja Aravindan, Natarajan Aravindan. Novel molecular targeted tumor targeted oncolytic peptide for the treatment of therapy resistant progressive neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB221.