Overcoming functional and translational challenges of cellular immunotherapies for solid tumors

In recent years, immunotherapy has revolutionized the landscape of cancer treatment, offering promising avenues for patients with otherwise limited outcomes. Among the most promising modalities are cell-based therapies, including autologous and allogeneic approaches such as engineered T cells, NK cells, stem cells and cell-based vaccines. These therapies harness the inherent capabilities of immune cells to recognize and eliminate cancer cells. Although cell therapies have shown remarkable clinical efficacy in hematologic malignancies, critical hurdles impede their efficacy for the treatment of solid tumors. This review examines the key challenges that hinder the broader clinical-translation of autologous and allogeneic cell-based cancer therapies in treating solid tumors. These include functional challenges that limit therapeutic efficacy and translational challenges that impede the clinical development and implementation of promising cellular therapies. We highlight contributing factors and evaluate potential solutions, emphasizing the synergistic potential of innovative engineering strategies, combination approaches, and emerging technologies to forge the next generation of cellular immunotherapies for solid tumors.