Delivery technologies for cancer immunotherapy

Abstract

Immunotherapy has become a powerful clinical strategy for treating cancer. The number of immunotherapy drug approvals has been increasing, with numerous treatments in clinical and preclinical development. However, a key challenge in the broad implementation of immunotherapies for cancer remains the controlled modulation of the immune system, as these therapeutics have serious adverse effects including autoimmunity and nonspecific inflammation. Understanding how to increase the response rates to various classes of immunotherapy is key to improving efficacy and controlling these adverse effects. Advanced biomaterials and drug delivery systems, such as nanoparticles and the use of T cells to deliver therapies, could effectively harness immunotherapies and improve their potency while reducing toxic side effects. Here, we discuss these research advances, as well as the opportunities and challenges for integrating delivery technologies into cancer immunotherapy, and we critically analyse the outlook for these emerging areas.

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Fig. 1: Paradigms in cancer nanomedicine.
Fig. 2: Barriers to mRNA cancer vaccine delivery to dendritic cells.
Fig. 3: Nanoparticles and nanoscale conjugates and delivery systems for cancer immunotherapy.
Fig. 4: Biomaterials for localized delivery of cancer immunotherapy.
Fig. 5: Delivery approaches for T cell-based immunotherapy.

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Acknowledgements

M.J.M. is supported by a Burroughs Wellcome Fund Career Award at the Scientific Interface, a US National Institutes of Health (NIH) Director’s New Innovator Award (DP2 TR002776) and a grant from the American Cancer Society (129784-IRG-16-188-38-IRG). R.S.R. is supported by an NIH T32 multidisciplinary training grant. The authors’ work is supported in part by Cancer Center Support (core) Grant P30-CA14051 from the US National Cancer Institute and a grant from the Koch Institute’s Marble Centre for Cancer Nanomedicine (to R.L.).

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R.S.R., C.H.J., R.L. and M.J.M. conceived the ideas, researched the data for the manuscript, discussed the manuscript content and wrote the manuscript. M.J.M. and R.S.R. designed the display items. All authors reviewed and edited the article before submission.

Correspondence to Robert Langer or Michael J. Mitchell.

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Competing interests

R.L. receives royalties from patents (as part of Massachusetts Institute of Technology (MIT) disbursements) that MIT has licensed or holds equity or receives consulting fees from Pfizer, Translate Bio, Editas, SQZ Biotech, Capio Biosciences, Combined Therapeutics, Moderna Therapeutics, Rubius Therapeutics, Tarveda Therapeutics and Verseau Therapeutics. C.H.J. works under a research collaboration involving the University of Pennsylvania and the Novartis Institutes of Biomedical Research, Inc. C.H.J. is an inventor of intellectual property licensed by the University of Pennsylvania to Novartis. C.H.J. has sponsored research and equity from Tmunity Therapeutics. C.H.J. is a consultant for Immune Design, Viracta and Carisma.

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Glossary

Cytokine release syndrome

Rapid release of cytokines leading to adverse symptoms such as increased heartbeat, nausea and low blood pressure.

Vascular leak syndrome

Increased vascular permeability that causes fluids from capillary vessels to enter tissues, which can lead to organ damage.

Dendritic cell

A type of antigen-presenting cell whose main function is to present antigens to T cells to modulate the immune system.

Regulatory T cells

A T cell population that maintains tolerance to self-antigens and prevents autoimmune disease.

Macrophages

A type of immune cell found at sites of infection and in tumour microenvironments.

Natural killer (NK) cells

A type of lymphocyte that can bind to and kill tumour cells.

Lymphocytes

A type of white blood cell found in the lymphatic system.

CD4+ T cells

T helper cells that regulate immune responses.

CD8+ T cells

Cytotoxic T cells that kill abnormal cells.

Antigen-presenting cells

(APCs). Immune cells that present antigens to T cells to modulate immune responses.

B cell aplasia

An adverse side effect of chimeric antigen receptor T cell therapy characterized by low numbers of B cells.

Click chemistry

A type of reaction commonly used for bioconjugation of molecules to delivery systems.

Dendrimers

A type of synthetic polymer with a branch-like structure.

Patient-derived xenograft (PDX) models

Cancer models in which patient-derived tumour tissue or cells are implanted into immunocompromised mice.

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