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Immune-checkpoint inhibitors and chimeric antigen receptor (CAR) T cells are revolutionizing oncology and haematology practice. With these and other immunotherapies, however, systemic biodistribution raises safety issues, potentially requiring the use of suboptimal doses or even precluding their clinical development. Delivering or attracting immune cells or immunomodulatory factors directly to the tumour and/or draining lymph nodes might overcome these problems. Hence, intratumoural delivery and tumour tissue-targeted compounds are attractive options to increase the in situ bioavailability and, thus, the efficacy of immunotherapies. In mouse models, intratumoural administration of immunostimulatory monoclonal antibodies, pattern recognition receptor agonists, genetically engineered viruses, bacteria, cytokines or immune cells can exert powerful effects not only against the injected tumours but also often against uninjected lesions (abscopal or anenestic effects). Alternatively, or additionally, biotechnology strategies are being used to achieve higher functional concentrations of immune mediators in tumour tissues, either by targeting locally overexpressed moieties or engineering 'unmaskable' agents to be activated by elements enriched within tumour tissues. Clinical trials evaluating these strategies are ongoing, but their development faces issues relating to the administration methodology, pharmacokinetic parameters, pharmacodynamic end points, and immunobiological and clinical response assessments. Herein, we discuss these approaches in the context of their historical development and describe the current landscape of intratumoural or tumour tissue-targeted immunotherapies.

Original publication

DOI

10.1038/s41571-021-00507-y

Type

Journal article

Journal

Nature reviews. Clinical oncology

Publication Date

09/2021

Volume

18

Pages

558 - 576

Addresses

Department of Immunology, Clínica Universidad de Navarra, Pamplona, Spain. imelero@unav.es.

Keywords

Animals, Humans, Mice, Neoplasms, Immunologic Factors, Antibodies, Monoclonal, Cytokines, Immunotherapy, Drug Delivery Systems, Injections, Intralesional, Tissue Distribution, Oncolytic Virotherapy, Molecular Targeted Therapy, Tumor Microenvironment, Antineoplastic Agents, Immunological