Therapeutic vaccines for breast cancer: Has the time finally come?

The ability to exploit the immune system as a weapon against cancer has revolutio-nised the treatment of cancer patients, especially through immune checkpoint inhibitors (ICIs). However, ICIs demonstrated a modest benefit in treating breast cancer (BC), with the exception of certain subsets of triple-negative BCs. An immune-suppressive tumour micro-environment (TME), typically present in BC, is an important factor in the poor response to immunotherapy.After almost two decades of poor clinical trial results, cancer vaccines (CVs), an active immunotherapy, have come back in the spotlight because of some technological advance-ments, ultimately boosted by coronavirus disease 2019 pandemic. In particular, neoantigens are emerging as the preferred targets for CVs, with gene-based and viral vector-based plat -forms in development. Moreover, lipid nanoparticles proved to be immunogenic and efficient delivery vehicles.Past clinical trials investigating CVs focused especially on the metastatic disease, where the TME is more likely compromised by inhibitory mechanisms. In this sense, favouring the use of CVs as monotherapy in premalignant or in the adjuvant setting and establishing combination treatments (i.e. CV plus ICI) in late-stage disease are promising strategies. This review pro-vides a full overview of the past and current breast cancer vaccine landscape.(c) 2021 Elsevier Ltd. All rights reserved.

Automated summary

The use of the immune system as a weapon against cancer, particularly through immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. However, the effectiveness of ICIs in treating breast cancer (BC) is limited, except for certain subsets of triple-negative BCs. The tumor microenvironment (TME), which is immune-suppressive in BC, plays a crucial role in the poor response to immunotherapy. Cancer vaccines (CVs), as active immunotherapy, have regained attention due to technological advancements and the COVID-19 pandemic, with a focus on neoantigens as preferred targets. Lipid nanoparticles have also shown promise as effective delivery vehicles for CVs. Past clinical trials mainly focused on metastatic disease, where the TME is more likely compromised by inhibitory mechanisms. Promising strategies include using CVs as monotherapy in premalignant or adjuvant settings, and combining CVs with ICIs in late-stage disease. This review provides a comprehensive overview of the current landscape of breast cancer vaccines.