Programmable local immunochemotherapy for triple-negative breast cancer via spatiotemporally controlled release of CpG oligodeoxynucleotides, gemcitabine, and paclitaxel

Programmable local immunochemotherapy for triple-negative breast cancer via spatiotemporally controlled release of CpG oligodeoxynucleotides, gemcitabine, and paclitaxel

  • Zagami, P. & Carey, L. A. Triple negative breast cancer: pitfalls and progress. NPJ Breast Cancer 8, 95 (2022).


    Google Scholar
     

  • Zerdan, M. B. et al. Triple negative breast cancer: updates on classification and treatment in 2021. Cancers 14, 1253 (2022).

  • Li, X. et al. Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res. Treat. 161, 279–287 (2017).


    Google Scholar
     

  • Hsu, J. Y., Chang, C. J. & Cheng, J. S. Survival, treatment regimens and medical costs of women newly diagnosed with metastatic triple-negative breast cancer. Sci. Rep. 12, 729 (2022).


    Google Scholar
     

  • Obidiro, O., Battogtokh, G. & Akala, E.O. Triple negative breast cancer treatment options and limitations: future outlook, Pharmaceutics 15, 1796 (2023).

  • Fan, Y. & He, S. The characteristics of tumor microenvironment in triple negative breast cancer. Cancer Manag. Res. 14, 1–17 (2022).


    Google Scholar
     

  • So, J. Y., Ohm, J., Lipkowitz, S. & Yang, L. Triple negative breast cancer (TNBC): non-genetic tumor heterogeneity and immune microenvironment: Emerging treatment options. Pharm. Ther. 237, 108253 (2022).


    Google Scholar
     

  • Harris, M. A. et al. Towards targeting the breast cancer immune microenvironment. Nat. Rev. Cancer 24, 554–577 (2024).


    Google Scholar
     

  • de Moraes, F. C. A., Souza, M. E. C., Sano, V. K. T., Moraes, R. A. & Melo, A. C. Association of tumor-infiltrating lymphocytes with clinical outcomes in patients with triple-negative breast cancer receiving neoadjuvant chemotherapy: a systematic review and meta-analysis. Clin. Transl. Oncol. 27, 974–987 (2024).

  • Leon-Ferre, R.A. & International Immuno-Oncology Biomarker Working Group. Tumor-infiltrating lymphocytes in triple-negative breast cancer. JAMA 331, 1135–1144 (2024).

  • Gao, G., Wang, Z., Qu, X. & Zhang, Z. Prognostic value of tumor-infiltrating lymphocytes in patients with triple-negative breast cancer: a systematic review and meta-analysis. BMC Cancer 20, 179 (2020).


    Google Scholar
     

  • Luo, C. et al. Progress and prospect of immunotherapy for triple-negative breast cancer. Front. Oncol. 12, 919072 (2022).


    Google Scholar
     

  • Zhu, Y., Zhu, X., Tang, C., Guan, X. & Zhang, W. Progress and challenges of immunotherapy in triple-negative breast cancer. Biochim. Biophys. Acta Rev. Cancer 1876, 188593 (2021).


    Google Scholar
     

  • Shewale, H. & Kanugo, A. Recent advances in immunotherapy and targeted therapy of triple negative breast cancer. Curr. Pharm. Biotechnol. 26, 365–391 (2024).

  • Liu, Y. et al. Advances in immunotherapy for triple-negative breast cancer. Mol. Cancer 22, 145 (2023).


    Google Scholar
     

  • Tarantino, P., Gandini, S., Trapani, D., Criscitiello, C. & Curigliano, G. Immunotherapy addition to neoadjuvant chemotherapy for early triple negative breast cancer: a systematic review and meta-analysis of randomized clinical trials. Crit. Rev. Oncol. Hematol. 159, 103223 (2021).


    Google Scholar
     

  • Huo, X. et al. Addition of immunotherapy to chemotherapy for metastatic triple-negative breast cancer: a systematic review and meta-analysis of randomized clinical trials. Crit. Rev. Oncol. Hematol. 168, 103530 (2021).


    Google Scholar
     

  • Howard, F. M., Pearson, A. T. & Nanda, R. Clinical trials of immunotherapy in triple-negative breast cancer. Breast Cancer Res. Treat. 195, 1–15 (2022).


    Google Scholar
     

  • Mittendorf, E. A. et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet 396, 1090–1100 (2020).


    Google Scholar
     

  • Schmid, P., Dent, R. & O’Shaughnessy, J. Pembrolizumab for early triple-negative breast cancer. N. Engl. J. Med. 382, e108 (2020).


    Google Scholar
     

  • Chen, W. et al. CpG-based nanovaccines for cancer immunotherapy. Int. J. Nanomed. 16, 5281–5299 (2021).


    Google Scholar
     

  • Rolfo, C., Giovannetti, E., Martinez, P., McCue, S. & Naing, A. Applications and clinical trial landscape using Toll-like receptor agonists to reduce the toll of cancer. NPJ Precis. Oncol. 7, 26 (2023).


    Google Scholar
     

  • Hsu, M. Y. et al. Enhanced paclitaxel efficacy to suppress triple-negative breast cancer progression using metronomic chemotherapy with a controlled release system of electrospun poly-d-l-lactide-co-glycolide (PLGA) nanofibers. Cancers 13, 3350 (2021).

  • Hu, Q. et al. A systematic review of gemcitabine and taxanes combination therapy randomized trials for metastatic breast cancer. SpringerPlus 3, 293 (2014).


    Google Scholar
     

  • Alfatama, M., Shahzad, Y. & Choukaife, H. Recent advances of electrospray technique for multiparticulate preparation: drug delivery applications. Adv. Colloid Interface Sci. 325, 103098 (2024).


    Google Scholar
     

  • Vigata, M., Meinert, C., Hutmacher, D. W. & Bock, N. Hydrogels as drug delivery systems: a review of current characterization and evaluation techniques. Pharmaceutics 12, 1188 (2020).

  • Bianchini, G., De Angelis, C., Licata, L. & Gianni, L. Treatment landscape of triple-negative breast cancer – expanded options, evolving needs. Nat. Rev. Clin. Oncol. 19, 91–113 (2022).


    Google Scholar
     

  • Bertucci, F. et al. Genomic characterization of metastatic breast cancers. Nature 569, 560–564 (2019).


    Google Scholar
     

  • Zhu, L. et al. Metastatic breast cancers have reduced immune cell recruitment but harbor increased macrophages relative to their matched primary tumors. J. Immunother. Cancer 7, 265 (2019).


    Google Scholar
     

  • Hutchinson, K. E. et al. Comprehensive profiling of poor-risk paired primary and recurrent triple-negative breast cancers reveals immune phenotype shifts. Clin. Cancer Res. 26, 657–668 (2020).


    Google Scholar
     

  • Cazzaniga, M.E. et al. Metronomic chemotherapy. Cancers 13, 2236 (2021).

  • Muraro, E. et al. Metronomic chemotherapy: anti-tumor pathways and combination with immune checkpoint inhibitors. Cancers 15 (2023).

  • Varayathu, H., Sarathy, V., Thomas, B. E., Mufti, S. S. & Naik, R. Combination strategies to augment immune check point inhibitors efficacy – implications for translational research. Front. Oncol. 11, 559161 (2021).


    Google Scholar
     

  • Tabata, Y. & Ikada, Y. Effect of the size and surface charge of polymer microspheres on their phagocytosis by macrophage. Biomaterials 9, 356–62 (1988).


    Google Scholar
     

  • Sarmadi, M. et al. Modeling, design, and machine learning-based framework for optimal injectability of microparticle-based drug formulations. Sci. Adv. 6, eabb6594 (2020).


    Google Scholar
     

  • Su, C. et al. Enhancing radiotherapy response via intratumoral injection of a TLR9 agonist in autochthonous murine sarcomas. JCI Insight. 9, e178767 (2024).

  • Dongye, Z. et al. Icaritin and intratumoral injection of CpG treatment synergistically promote T cell infiltration and antitumor immune response in mice. Int. Immunopharmacol. 111, 109093 (2022).


    Google Scholar
     

  • Liu, J. et al. Programmable delivery of immune adjuvant to tumor-infiltrating dendritic cells for cancer immunotherapy. Nano Lett. 20, 4882–4889 (2020).


    Google Scholar
     

  • Kadiyala, P. et al. High-density lipoprotein-mimicking nanodiscs for chemo-immunotherapy against glioblastoma multiforme. ACS Nano 13, 1365–1384 (2019).

  • Shirota, Y., Shirota, H. & Klinman, D. M. Intratumoral injection of CpG oligonucleotides induces the differentiation and reduces the immunosuppressive activity of myeloid-derived suppressor cells. J. Immunol. 188, 1592–9 (2012).


    Google Scholar
     

  • Ali, H. R. et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Ann. Oncol. 25, 1536–43 (2014).


    Google Scholar
     

  • Patras, L., Shaashua, L., Matei, I. & Lyden, D. Immune determinants of the pre-metastatic niche. Cancer Cell 41, 546–572 (2023).


    Google Scholar
     

  • Wang, Y. et al. Pre-metastatic niche: formation, characteristics and therapeutic implication. Signal Transduct. Target Ther. 9, 236 (2024).


    Google Scholar
     

  • Keklikoglou, I. et al. Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models. Nat. Cell Biol. 21, 190–202 (2019).


    Google Scholar
     

  • Monteran, L. et al. Chemotherapy-induced complement signaling modulates immunosuppression and metastatic relapse in breast cancer. Nat. Commun. 13, 5797 (2022).


    Google Scholar
     

  • Karagiannis, G. S., Condeelis, J. S. & Oktay, M. H. Chemotherapy-induced metastasis: mechanisms and translational opportunities. Clin. Exp. Metastasis 35, 269–284 (2018).


    Google Scholar
     

  • Nishikawa, M. et al. Biodegradable CpG DNA hydrogels for sustained delivery of doxorubicin and immunostimulatory signals in tumor-bearing mice. Biomaterials 32, 488–94 (2011).


    Google Scholar
     

  • Hsu, M. Y. et al. Preparation and in vitro/in vivo evaluation of doxorubicin-loaded poly[lactic-co-glycol acid] microspheres using electrospray method for sustained drug delivery and potential intratumoral injection. Colloids Surf. B Biointerfaces 190, 110937 (2020).