Intratumoural administration and tumour tissue targeting of cancer immunotherapies.

Autor: Melero I; Department of Immunology, Clínica Universidad de Navarra, Pamplona, Spain. imelero@unav.es.; Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain. imelero@unav.es.; Program for Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain. imelero@unav.es.; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. imelero@unav.es.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. imelero@unav.es., Castanon E; Department of Immunology, Clínica Universidad de Navarra, Pamplona, Spain.; Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain., Alvarez M; Program for Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Champiat S; Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Université Paris Saclay, Gustave Roussy, Villejuif, France.; INSERM U1015, Gustave Roussy, Villejuif, France.; Biotherapies for In Situ Antitumor Immunization (BIOTHERIS), Centre d'Investigation Clinique INSERM CICBT1428, Villejuif, France., Marabelle A; Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Université Paris Saclay, Gustave Roussy, Villejuif, France. aurelien.marabelle@gustaveroussy.fr.; INSERM U1015, Gustave Roussy, Villejuif, France. aurelien.marabelle@gustaveroussy.fr.; Biotherapies for In Situ Antitumor Immunization (BIOTHERIS), Centre d'Investigation Clinique INSERM CICBT1428, Villejuif, France. aurelien.marabelle@gustaveroussy.fr.
Jazyk: angličtina
Zdroj: Nature reviews. Clinical oncology [Nat Rev Clin Oncol] 2021 Sep; Vol. 18 (9), pp. 558-576. Date of Electronic Publication: 2021 May 18.
DOI: 10.1038/s41571-021-00507-y
Abstrakt: 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.
(© 2021. Springer Nature Limited.)
Databáze: MEDLINE
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