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• W3135590981 abstract "382 Objectives: Despite the advance of targeted therapies on various tumors, prognosis of patients with triple negative breast cancer (TNBC) in both the early and advanced-stages of the disease still remains poor due to the severe lack of actionable molecular targets on the TNBC. The consensus that angiogenesis highly associates with growth of the solid tumors fosters our proposition to develop angiogenic receptor-targeted radionuclide therapy (TRT) to treat TNBC by specifically delivering the ionic energy to the neoplastic malformations. Meanwhile, numerous preclinical and clinical studies have shown remarkable anti-tumor efficacy of immune checkpoint blockade immunotherapy on a broad range of tumor types. However, the response is limited to a minority of patients and indications. A question has been raised among radiologists and oncologists whether combination of the TRT and immunotherapy will further benefit effectiveness of the treatment especially for TNBC patients. Methods: High affinity synthetic VEGFR-targeted agent, diZD, was radiolabelled with 177Lu to construct the TRT agent. Two doses of 177Lu-diZD were given (once a week) to mice implanted with orthotropic 4T1 tumors to impart TRT for the treatment, while the combination with immunotherapy was initiated in the same time window by four doses of anti-PD1 antibody given to the tumor-bearing mice. Afterwards, tumor growth and animal survivals were monitored until the end of the study. Outcomes of animals only receiving either of the individual therapy were compared in parallel with the animals receiving the combined therapies. Results: Median survival for the 4T1-bearing mice treated with 177Lu-diZD based TRT was 28 days, which was significantly prolonged than control group of 18 days. Accordingly, promising local tumor control was observed as well. Prognosis of the mice with TNBC remained poor with median survival of 16 days upon the treatment of anti-PD1 antibody-based immunotherapy, which was correlate with reported study for anti-PD1 therapy for TNBC. Surprisingly, combination of the two therapies did not further improve the TRT, on the contrary, it significantly reduced the median survival of TRT from 28 days to 20 days on the treatment to the TNBC mice. Further analysis revealed negligible expression of PD1 receptor on the T cells of the TNBC mice, which supported the poor response of the TNBC to the anti-PD1 im munotherapy. Conclusions: The VEGFR-oriented TRT posed a promising therapeutic option to treat TNBC. Our study showed additionally imposed immunotherapy to “cold” tumors could diminished the therapeutic outcome yielded upon the TRT. The clinical consensus that the combination of TRT and immunotherapy synergistically enhances anti-tumor efficacy should be revisited." @default.
• W3135590981 created "2021-03-15" @default.
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• W3135590981 date "2020-05-01" @default.
• W3135590981 modified "2023-09-25" @default.
• W3135590981 title "Small molecule-based angiogenic radionuclide radiation therapy combined with anti-PD1 immune checkpoint blockade for triple-negative breast cancer" @default.
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