Abstract Cell-based immunotherapies offer a powerful means to harness treatment-induced antitumor immunity for durable tumor control. We previously developed a Triple-Therapy (TT) regimen combining vinorelbine-mediated activation of antigen-presenting cells (APCs) with cyclophosphamide-driven induction of TCF1+ stem-cell-like T cells (scTs), markedly enhancing anti-PD-1 efficacy in resistant tumor models. The TT protocol consists of three intermittent doses of vinorelbine, and cyclophosphamide administered every six days, together with five anti-PD-1 doses delivered every two days.In a Non-Hodgkin Lymphoma (NHL) model, TT not only achieved strong tumor regression but also conferred long-term immunological memory, as evidenced by protection upon tumor rechallenge. Extending these findings to triple-negative breast cancer (TNBC), TT induced comparable antitumor activity. To determine whether TT-elicited immunity could be adoptively transferred, immunocompetent BALB/c mice bearing 4T1 TNBC were treated with TT, and immune tissues—including blood, spleen, and lymph nodes—were collected and transferred into syngeneic BALB/c nude mice inoculated with the same tumor.Strikingly, transfer of peripheral blood from TT-treated donors significantly delayed tumor growth, indicating that circulating immune cells are sufficient to convey protection. In contrast, lymphocyte depletion abolished this effect. Selective ablation of CD4+ or CD8+ T cells—performed either by flow cytometric sorting or using neutralizing antibodies—also eliminated the therapeutic benefit, confirming their essential role in the transferable antitumor response.Overall, these findings demonstrate that TT induces systemic, memory-forming T-cell responses capable of mediating cell-transferable tumor control. Current work focuses on identifying the tumor antigens recognized by TT-induced T cells, with the ultimate goal of developing targeted therapeutic vaccines to extend these benefits to broader patient populations. Citation Format: Stefania Orecchioni, D'Ambrosio Lorenzo, Davide Lombardi, Anna Vaccari, Paola Nistico', Francesco Bertolini, Paolo Falvo. Intermittent cyclophosphamide and vinorelbine combined with anti-PD-1 induce transferable T-cell-mediated antitumor immunity and long-term memory in TNBC mouse models abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5627.
Orecchioni et al. (Fri,) studied this question.