Photothermal Therapy Promotes Tumor Infiltration and Antitumor Activity of CAR T Cells

Chen, Qian; Hu, Quanyin; Dukhovlinova, Elena; Chen, Guojun; Ahn, Sarah; Wang, Chao; Ogunnaike, Edikan A.; Ligler, Frances S.; Dotti, Gianpietro; Gu, Zhen

doi:10.1002/adma.201900192

Cited by 334 publications

(251 citation statements)

References 36 publications

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“…In vivo FL imaging showed that the ICG FL signal was significantly attenuated after laser irradiation (660 and 808 nm), mainly due to the quenching of the ICG signal caused by laser irradiation. However, the FL signal of ICG recovered 3 h after laser irradiation, which might be due to an S/HSA/ICG‐mediated optical intervention that promoted vasodilation and reduced tumor compact structure, thereby promoting more S/HSA/ICG accumulation in tumors. Syne with laser irradiation did not significantly inhibit tumor growth.…”

Section: Resultsmentioning

confidence: 99%

In Situ Photocatalyzed Oxygen Generation with Photosynthetic Bacteria to Enable Robust Immunogenic Photodynamic Therapy in Triple‐Negative Breast Cancer

Liu

Luo

et al. 2020

Adv Funct Materials

132

104

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Hypoxia in the tumor microenvironment is a major hurdle dampening the antitumor effect of photodynamic therapy (PDT). Herein, active photosynthetic bacteria (Synechococcus 7942, Syne) are utilized for tumor‐targeted photosensitizer delivery and in situ photocatalyzed oxygen generation to achieve photosynthesis‐boosted PDT. Photosensitizer‐encapsulated nanoparticles (HSA/ICG) are assembled by intermolecular disulfide crosslinking and attached to the surface of Syne with amide bonds to form a biomimetic system (S/HSA/ICG). S/HSA/ICG combined the photosynthetic capability of Syne and the theranostic effect of HSA/ICG. Syne capable of photoautotrophy exhibit a moderate immune stimulation effect and a certain photodynamic role under 660 nm laser irradiation. Upon intravenous injection into tumor‐bearing mice, S/HSA/ICG can effectively accumulate in tumors and generate oxygen continuously under laser irradiation through photosynthesis, which remarkably relieve tumor hypoxia and enhance reactive oxygen species production, thereby completely eliminating primary tumors. This photosynthesis‐boosted PDT can also effectively reverse the tumor immunosuppressive microenvironment and robustly evoke systematic antitumor immune responses, which exhibit excellent effect on preventing tumor recurrence and metastasis inhibition in a metastatic triple‐negative breast cancer mouse model. Hence, this photosynthetic bacteria‐based photosynthesis‐boosted immunogenic PDT offers a promising approach to eliminate both local and metastatic tumors.

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Section: Resultsmentioning

confidence: 99%

In Situ Photocatalyzed Oxygen Generation with Photosynthetic Bacteria to Enable Robust Immunogenic Photodynamic Therapy in Triple‐Negative Breast Cancer

Liu

Luo

et al. 2020

Adv Funct Materials

132

104

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“…Gu et al proposed photothermal nanoparticles of poly(lactic‐ co ‐glycolic) acid (PLGA) loaded with indocyanine green (ICG), to precondition the solid tumor under the near‐infrared (NIR) light irradiation. [ 31 ] The mild hyperthermia of the tumor reduced its compact structure and interstitial fluid pressure (IFP), increased blood perfusion, released antigens, and promoted the recruitment of endogenous immune cells ( Figure A). These effects promoted the penetration and therapeutic index of CAR‐T cells in solid tumors (Figure 6B).…”

Section: Nanoparticles As a Potent Platform For Reprogramming Tumor‐amentioning

confidence: 99%

“…[ 28 ] In addition to their roles in the suppression of immune response and the inhibition of cytotoxic T cell proliferation, [ 29 ] these critical features of the TME allow tumors to actively escape T‐cell‐mediated tumor‐specific immunity, by activating negative regulatory pathways (checkpoints) such as programmed cell death protein‐1 (PD‐1). [ 30 ] Abnormal tumor vessels (leaky, tortuous, and dilated blood vessels) may also create a physiological barrier to CAR‐T cell trafficking and infiltration, [ 31 ] and facilitate immune evasion. [ 32 ]…”

Section: Introductionmentioning

confidence: 99%

Nanotechnology Promotes Genetic and Functional Modifications of Therapeutic T Cells Against Cancer

Abdalla

Xiao

et al. 2020

Advanced Science

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Growing experience with engineered chimeric antigen receptor (CAR)‐T cells has revealed some of the challenges associated with developing patient‐specific therapy. The promising clinical results obtained with CAR‐T therapy nevertheless demonstrate the urgency of advancements to promote and expand its uses. There is indeed a need to devise novel methods to generate potent CARs, and to confer them and track their anti‐tumor efficacy in CAR‐T therapy. A potentially effective approach to improve the efficacy of CAR‐T cell therapy would be to exploit the benefits of nanotechnology. This report highlights the current limitations of CAR‐T immunotherapy and pinpoints potential opportunities and tremendous advantages of using nanotechnology to 1) introduce CAR transgene cassettes into primary T cells, 2) stimulate T cell expansion and persistence, 3) improve T cell trafficking, 4) stimulate the intrinsic T cell activity, 5) reprogram the immunosuppressive cellular and vascular microenvironments, and 6) monitor the therapeutic efficacy of CAR‐T cell therapy. Therefore, genetic and functional modifications promoted by nanotechnology enable the generation of robust CAR‐T cell therapy and offer precision treatments against cancer.

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“…Table attempts to summarize the more combinatorial strategies explored so far by different investigators in achieving improve and long‐lasting therapeutic effects by combining PTT and immunotherapy.…”

Section: Evidence Of Nanoparticle‐mediated Photoimmunotherapy For Indmentioning

confidence: 99%

Immunological Consequences of Nanoparticle‐Mediated Antitumor Photoimmunotherapy

Hameed

Mustafa

et al. 2019

Advanced Therapeutics

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Conventional phototherapies have been thought to destroy the malignant cells through apoptosis or necrosis, shut down tumor microvasculature, and activate the host immune system. Accumulating evidence indicates that photothermal agents stimulate both innate and adaptive arms of host immune systems by i) priming tumor antigen-specific T-cell responses, ii) attracting lymphocytes into the tumor site, and iii) modulation of the tumor microenvironment (TME). However, the salutary effect of traditional phototherapies is hindered by its limited penetration depth in tissues. Recent advances in cancer immunotherapies have significantly transformed the landscape of cancer treatment from conventional phototherapies to most standard cancer therapy regimen. Therefore, phototherapies synergized with immunotherapy, maximize the anticancer efficacy by overcoming immunosuppressive TME and elucidating immune responses outside the irradiation area. This synergism is further strengthened by nanomaterial-based strategies to form innovative nanocarriers for efficient and simultaneous delivery of photosensitizers and immunomodulators at the desired target. These nanocarriers can improve the accumulation and retention of both photosensitizer and immunomodulators within the target location, thereby enhancing safety and efficacy. Herein, the systematic effects of phototherapies on the immune system are summarized and the ways in which nanomaterial-based photoimmunotherapy can facilitate the eradication of both primary and metastatic tumors are discussed.

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Photothermal Therapy Promotes Tumor Infiltration and Antitumor Activity of CAR T Cells

Cited by 334 publications

References 36 publications

In Situ Photocatalyzed Oxygen Generation with Photosynthetic Bacteria to Enable Robust Immunogenic Photodynamic Therapy in Triple‐Negative Breast Cancer

In Situ Photocatalyzed Oxygen Generation with Photosynthetic Bacteria to Enable Robust Immunogenic Photodynamic Therapy in Triple‐Negative Breast Cancer

Nanotechnology Promotes Genetic and Functional Modifications of Therapeutic T Cells Against Cancer

Immunological Consequences of Nanoparticle‐Mediated Antitumor Photoimmunotherapy

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