Adoptive T cell therapy: An overview of obstacles and opportunities

Baruch, Erez N.; Berg, A.; Besser, Michal J.; Schachter, Jacob; Markel, Gal

doi:10.1002/cncr.30491

Cited by 82 publications

(71 citation statements)

References 94 publications

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“…The furthest‐developed one in clinic is called a chimeric antigen receptor (CAR). After such a selection, these cells are stimulated to expand in vitro and finally reinfused back to the cancer patient . However, the immune response induced by this approach is limited due to a large amount of ex vivo proliferation (up to 10 11 T cells) and immunosuppressive tumor microenvironment …”

Section: Developing Novel Nanoplatforms For Stimulating Cellular Immumentioning

confidence: 99%

“…After such a selection, these cells are stimulated to expand in vitro and finally reinfused back to the cancer patient. [208] However, the immune response induced by this approach is limited due to a large amount of ex vivo proliferation (up to 10 11 T cells) and immunosuppressive tumor microenvironment. [209] To rapidly expand effector cells into the required quantity, iron-dextran-derived nano-aAPCs were used to selectively bind to tumor specific T cells from the naïve precursors through magnetic force, followed by the elution and extensive culture of positive fractions.…”

Section: Adoptive T Cell Cancer Therapy Enhanced By Nanoparticle-thermentioning

confidence: 99%

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Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Liu

Zhang

2019

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Cancer immunotherapy is a promising cancer terminator by directing the patient's own immune system in the fight against this challenging disorder. Despite the monumental therapeutic potential of several immunotherapy strategies in clinical applications, the efficacious responses of a wide range of immunotherapeutic agents are limited in virtue of their inadequate accumulation in the tumor tissue and fatal side effects. In the last decades, increasing evidences disclose that nanotechnology acts as an appealing solution to address these technical barriers via conferring rational physicochemical properties to nanomaterials. In this Review, an imperative emphasis will be drawn from the current understanding of the effect of a nanosystem's structure characteristics (e.g., size, shape, surface charge, elasticity) and its chemical modification on its transport and biodistribution behavior. Subsequently, rapid‐moving advances of nanoparticle‐based cancer immunotherapies are summarized from traditional vaccine strategies to recent novel approaches, including delivery of immunotherapeutics (such as whole cancer cell vaccines, immune checkpoint blockade, and immunogenic cell death) and engineered immune cells, to regulate tumor microenvironment and activate cellular immunity. The future prospects may involve in the rational combination of a few immunotherapies for more efficient cancer inhibition and elimination.

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Section: Developing Novel Nanoplatforms For Stimulating Cellular Immumentioning

confidence: 99%

Section: Adoptive T Cell Cancer Therapy Enhanced By Nanoparticle-thermentioning

confidence: 99%

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Liu

Zhang

2019

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116

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“…Additional alternative strategies in cancer immunotherapy include vaccines or cellular therapies, for example, with tumour-infiltrating lymphocytes (TIL) 19 or autologous T cells genetically modified to express chimeric antigen receptors (CAR T cells). 20 BC was initially considered as a non-immunogenic tumour, but recent studies have demonstrated that the expression of immune-related genes and the presence of immune infiltrates in primary tumours were associated with a better clinical outcome, [21][22][23][24][25][26][27] particularly in the most aggressive subtypes (HER2-positive and triple-negative (TNBC)). In addition, and consistent with their function, specific subsets of immune cells were correlated with outcome in BC.…”

Section: Introductionmentioning

confidence: 99%

Targeting immune checkpoints in breast cancer: an update of early results

et al. 2017

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The immune tumour microenvironment has been shown to play a crucial role in the development and progression of cancer. Expression of gene signatures, reflecting immune activation, and the presence of tumour-infiltrating lymphocytes were associated with favourable outcomes in HER2-positive and triple-negative breast cancer. Recently, immunotherapy with immune checkpoint blockade induced long-lasting responses and improved survival in hard-to-treat malignancies (ie, melanoma and non-small cell lung cancer) and are changing treatment paradigms in a variety of neoplastic diseases. Immune checkpoint blockade has been evaluated in breast cancer, particularly in the triple-negative subtype, with promising results observed in monotherapy or in combination with chemotherapy in the metastatic and neoadjuvant settings. However, identification of patients who are most likely to benefit from immune checkpoint blockade remains challenging, with many patients not responding to treatments and a significant financial cost. The combination of immune checkpoint blockade with conventional cancer treatments such as chemotherapy, radiotherapy, targeted therapies or with other immunotherapies is a promising strategy to potentiate its efficacy in breast cancer although further research is required to effectively identify who will respond to these immunotherapies. In this review we report the most recent results that emerged from trials testing immune checkpoint blockade and potential predictive biomarkers and emphasise the new strategies that are under clinical development in breast cancer.

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“…Nevertheless, in the combined immunotherapy setting with PD-1 blockade and CD137 agonism, AT-3 tumors were not eliminated, despite a robust CTL response. This problem is also evident in cancer patients that fail to respond to adoptive tumor-specific T-cell therapy (Baruch et al, 2017), highlighting that T-cell suppression in the TME can pose an additional bottleneck for systemic anti-tumor immunity. Importantly, our study demonstrates that radiotherapy can alter the state of the TME to permit effective CTL activity, where PD-1 blockade cannot.…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy and cisplatin increase immunotherapy efficacy by enabling local and systemic intratumoral T-cell activity

Kroon

Frijlink

Iglesias-Guimarais

et al. 2018

Preprint

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This study reveals that radiotherapy and cisplatin can be 're-purposed' to improve antibody-based immunotherapy success in poorly immunogenic breast cancer by overruling PD-1 unrelated mechanisms of T cell suppression in the tumor micro-environment. AbstractTo increase cancer immunotherapy success, PD-1 blockade must be combined with rationally selected treatments. Here, we examined in a poorly immunogenic mouse breast cancer model the potential of antibody-based immunomodulation and conventional anti-cancer treatments to collaborate with anti-PD-1 treatment. One important requirement to improve anti-PD-1-mediated tumor control was to promote tumorspecific cytotoxic T cell (CTL) priming, which was achieved by stimulating the CD137 costimulatory receptor.A second requirement was to overrule PD-1-unrelated mechanisms of CTL suppression in the tumor microenvironment (TME). This was achieved by radiotherapy and cisplatin treatment. In the context of CD137/PD-1-targeting immunotherapy, radiotherapy allowed for tumor elimination by altering the TME, rather than intrinsic CTL functionality. Combining this radioimmunotherapy regimen with low-dose cisplatin improved CTL-dependent regression of a contralateral tumor outside the radiation field. Thus, systemic tumor control may be achieved by combining immunotherapy protocols that promote T cell priming with (chemo)radiation protocols that permit CTL activity in both the irradiated tumor and (occult) metastases. IntroductionCancer immunotherapies include adoptive T-cell therapy, therapeutic vaccination, and/or antibody-based immunomodulation. From a technical perspective, antibody-based immunomodulation is relatively straightforward, since immunomodulatory antibodies can essentially be delivered in the same way as conventional anti-cancer drugs. The immunomodulatory antibodies that have been approved for cancer immunotherapy are designed to target the T-cell coinhibitory receptors PD-1 or CTLA-4, and both single or combined treatment induces durable responses in up to 32% of patients with solid tumors (Iwai et al., 2017).Still, the majority of patients do not benefit from this treatment approach . Compared to targeting CTLA-4, targeting PD-1 is generally more successful and is associated with fewer autoimmune symptoms (Buchbinder and Desai, 2016). Therefore, targeting PD-1 currently serves as the backbone for developing new combination therapies in order to improve patient response rates. To choose combinations rationally, insight into their combined mechanism of action is required. Successful immunotherapy relies on the activity of T cells. Upon activation bytumor-specific antigens, CD8 + T cells develop into CTLs that can recognize tumor-derived (intracellular) peptides that are presented on the cell surface by MHC class I molecules. As MHC class I molecules are expressed on virtually all body cells, CTLs can in principle target any cancer type. CD4 + T cells also promote anti-tumor immunity, either by direct cytotoxic activity or by promoting the activity of CTLs and oth...

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Adoptive T cell therapy: An overview of obstacles and opportunities

Cited by 82 publications

References 94 publications

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Targeting immune checkpoints in breast cancer: an update of early results

Radiotherapy and cisplatin increase immunotherapy efficacy by enabling local and systemic intratumoral T-cell activity

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