{
  "abstract": "Background Chimeric antigen receptor (CAR) therapies have revolutionized cancer immunotherapy, particularly in hematologic malignancies, but their efficacy in solid tumors remains limited. Key barriers include tumor antigen heterogeneity, on-target/off-tumor toxicity, impaired trafficking, and an immunosuppressive tumor microenvironment.Methods We conducted a narrative review of preclinical and clinical studies investigating CAR-engineered innate and innate-like immune cells, including CAR-natural killer, CAR-γδ T, CAR-natural killer T (NKT), and CAR-macrophages, focusing on their biological features, therapeutic potential, and current clinical development in solid tumors.Results These alternative platforms exhibit distinct advantages over conventional CAR-T cells, including reduced risk of severe toxicities, improved trafficking, overcoming antigen loss, and higher allogeneic potential. Emerging clinical data suggest favorable safety profiles, although limited persistence and variable efficacy remain key challenges. Advances in cell engineering, such as cytokine armoring and non-viral gene transfer, are further enhancing their therapeutic potential.Conclusions CAR-engineered innate and innate-like immune cells represent a promising next-generation strategy to overcome the limitations of conventional CAR-T therapies in solid tumors. Among these, CAR-NKT and CAR-γδ T cells may offer particular advantages for clinical translation, warranting further investigation in future trials.",
  "authors": [
    {
      "affiliations": [
        "Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"
      ],
      "name": "Giuseppe Nardo"
    },
    {
      "affiliations": [
        "Unit of Immunotherapy and Anticancer Innovative Therapeutics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"
      ],
      "name": "Francesca Putti"
    },
    {
      "affiliations": [
        "Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy",
        "Unit of Melanoma Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"
      ],
      "name": "Alice Indini"
    },
    {
      "affiliations": [
        "Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy",
        "Unit of Melanoma Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"
      ],
      "name": "Michele Del Vecchio"
    },
    {
      "affiliations": [
        "Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy",
        "Medical Oncology and Hematology Department, University of Milan, Milan, Italy",
        "Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"
      ],
      "name": "Filippo De Braud"
    },
    {
      "affiliations": [
        "Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy",
        "Unit of Immunotherapy and Anticancer Innovative Therapeutics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"
      ],
      "name": "Massimo Di Nicola"
    },
    {
      "affiliations": [
        "Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy",
        "Unit of Immunotherapy and Anticancer Innovative Therapeutics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"
      ],
      "name": "Francesca De Santis"
    }
  ],
  "title": "CAR-engineering of innate and innate-like immune cells: a new horizon in adoptive cell therapy for solid tumors",
  "uid": "d73dd89a-2b43-5784-846d-fa8459c2ba57"
}