Search

Despite marked advancements in cancer immunotherapy over the past few decades, there remains an urgent need to develop more effective treatments in humans. This review explores strategies to overcome hurdles in cancer immunotherapy, leveraging innovative technologies including multi-specific antibodies, chimeric antigen receptor (CAR) T cells, myeloid cells, cancer-associated fibroblasts, artificial intelligence (AI)-predicted neoantigens, autologous vaccines, and mRNA vaccines. These approaches aim to address the diverse facets and interactions of tumors' immune evasion mechanisms. Specifically, multi-specific antibodies and CAR T cells enhance interactions with tumor cells, bolstering immune responses to facilitate tumor infiltration and destruction. Modulation of myeloid cells and cancer-associated fibroblasts targets the tumor's immunosuppressive microenvironment, enhancing immunotherapy efficacy. AI-predicted neoantigens swiftly and accurately identify antigen targets, which can facilitate the development of personalized anticancer vaccines. Additionally, autologous and mRNA vaccines activate individuals' immune systems, fostering sustained immune responses against cancer neoantigens as therapeutic vaccines. Collectively, these strategies are expected to enhance efficacy of cancer immunotherapy, opening new horizons in anticancer treatment., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Jihyun Kim et al.)

T cells and macrophages have the potential to collaborate to eliminate tumor cells efficiently. Macrophages can eliminate tumor cells through phagocytosis and subsequently activate T cells by presenting tumor antigens. The activated T cells, in turn, can kill tumor cells and redirect tumor-associated macrophages toward an antitumoral M1 phenotype. However, checkpoint molecules expressed on tumor cells impede the collaborative action of these immune cells. Meanwhile, monotherapy with a single immune checkpoint inhibitor (ICI) for either macrophages or T cells yields suboptimal efficacy in cancer patients. To address this challenge, here a nanoparticle capable of efficiently delivering dual ICIs to tumors for both macrophages and T cells is developed. These programmed cell death protein 1 (PD-1)-transfected macrophage membrane-derived nanoparticles (PMMNPs) can target tumors and provide signal-regulatory protein alpha and PD-1 to block CD47 and programmed cell death-ligand 1 (PD-L1), respectively, on tumor cells. PMMNPs enhance macrophage-mediated cancer cell phagocytosis and antigen presentation, promote T cell activation, and induce the reprogramming of macrophages toward an antitumoral phenotype. In syngeneic tumor-bearing mice, PMMNPs demonstrate superior therapeutic efficacy compared to nanoparticles delivering single ICIs and non-targeted delivery of anti-CD47 and anti-PD-L1 antibodies. PMMNPs capable of augmenting the antitumoral interplay between macrophages and T cells may offer a promising avenue for cancer immunotherapy., (© 2024 Wiley‐VCH GmbH.)