Intratumoural administration and tumour tissue targeting of cancer immunotherapies

May 19, 2021Nature reviews. Clinical oncology

Injecting cancer immunotherapies directly into tumors and targeting them to tumor tissue

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Abstract

Intratumoural delivery of immune therapies may significantly enhance their efficacy against tumors.

Systemic biodistribution of immune-checkpoint inhibitors and CAR T cells raises safety concerns.
Directly targeting immune cells or factors to tumors could improve the bioavailability of immunotherapies.
In mouse models, intratumoural administration of various agents has shown powerful effects on both injected and uninjected tumors.
Biotechnology strategies aim to achieve higher concentrations of immune mediators in tumor tissues by targeting specific elements or using specially designed agents.
Ongoing clinical trials are assessing these strategies but face challenges related to administration methods and response evaluations.

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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.

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Intratumoural administration and tumour tissue targeting of cancer immunotherapies

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