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cyclophosphamide + vincristine + topotecan + allogeneic NK cells + 3F8

Development stage
Preclinical
Lead developer
Memorial Sloan Kettering Cancer Center
Modality
Small Molecules, CAR-NK Cells → Other Engineered Cells → Adoptive Cell Transfer → Cell Therapies, Monoclonal Antibodies → Antibody-Based Therapeutics, Lymphokine-Activated Killer Cells → Native Immune Cells → Adoptive Cell Transfer → Cell Therapies
Administration
Intravenous
01

Overview

This is a multi-agent investigational combination therapy comprising three chemotherapeutic agents (cyclophosphamide, vincristine, and topotecan), allogeneic natural killer (NK) cell therapy, and the murine monoclonal antibody 3F8. Cyclophosphamide is an alkylating agent that crosslinks DNA to inhibit cell division. Vincristine is a vinca alkaloid that disrupts microtubule formation during mitosis. Topotecan inhibits topoisomerase I, leading to DNA damage in dividing cells[1][2][5]. Allogeneic NK cell therapy involves the infusion of donor-derived natural killer cells to enhance immune-mediated tumor cytotoxicity. 3F8 is a murine IgG3 monoclonal antibody targeting ganglioside GD2, which is highly expressed on neuroblastoma and some other tumors; it mediates antitumor effects via complement activation and antibody-dependent cellular cytotoxicity (ADCC)[6][8][10]. This combination aims to maximize direct cytotoxic effects on tumor cells while leveraging both innate (NK cell) and adaptive (antibody-mediated) immune responses.

02

Targets

TUBB (Tubulin (alpha and beta subunits))TOP1 (DNA Topoisomerase I)GD2DNA

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