Pilot study of adoptive immunotherapy with sentinel node-derived T cells in muscle-invasive urinary bladder cancer

Sherif, Amir; Hasan, Mudhar N.; Radecka, Eva; Rodríguez, Álvaro Lozano; Shabo, S.; Karlsson, Matilda; Schumacher, Martin; Marits, Per; Winqvist, Ola

doi:10.3109/21681805.2015.1059880

Cited by 14 publications

(14 citation statements)

References 34 publications

(40 reference statements)

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“…Indeed, CD4 + T cells have been demonstrated to promote tumor eradication through this feature, mediated partly by their ability to secrete IL-2 (142). Consistently, there are successful examples of the clinical use of CD4 + Teff cells in cancer immunotherapies, including ACT, as we have previously reported for in UBC (143) and others for melanoma (144). Taken together, CD4 + Teff cells, particularly the Th1 subset, reinforce multiple distinct aspects of the anti-tumor immune response, suggesting an underestimated potential of this cell compartment for the use in cancer immunotherapies.…”

Section: Anti-cancer Responses By Effector Cd8 + and Cd4 + T Cellssupporting

confidence: 66%

“…As discussed previously, immune responses are in general initiated in the lymph node. This notion combined with the hypothesis that immunosuppression would be less pronounced in the tumordraining lymph node, is the foundation for our groups' focus on this anatomical location, because it represents an alternative source for ACT (143). However, because tumors may induce neolymphangiogenesis, the lymphatic drainage system is frequently deranged which complicates the identification of this node(s).…”

Section: The Sentinel Node a Key Component Of The Tumor Microenvironmentioning

confidence: 99%

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Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer

et al. 2018

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Section: Anti-cancer Responses By Effector Cd8 + and Cd4 + T Cellssupporting

confidence: 66%

Section: The Sentinel Node a Key Component Of The Tumor Microenvironmentioning

confidence: 99%

Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer

et al. 2018

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“…In this approach, lymphocytes are harvested and expanded, then re-infused into the patient. In UBC, a pilot study of infusion of T cells that were expanded ex-vivo from tumor draining lymph nodes reported 2 out of 6 patients with responses [34]. This process may be enhanced through genetic engineering of T cells to express chimeric antigen receptors (CARs).…”

Section: Therapeutic Targeting Of Dysfunctional Anti-tumor Immunitymentioning

confidence: 99%

Emerging role of immunotherapy in urothelial carcinoma—Immunobiology/biomarkers

Sweis

Galsky

2016

Urologic Oncology: Seminars and Original Investigations

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Urothelial bladder cancer is one of the first cancers recognized to be immunogenic since 40 years ago when the use of bacillus Calmette–Guerin (BCG) was shown to prevent recurrence. Since that time, our knowledge of immune biology of cancer has expanded tremendously, and bladder cancer patients finally have new active immunotherapeutic drugs with on the horizon. Anti-programmed cell death-1 (PD-1)/(programmed cell death ligand-1 (PD-L1) therapy has shown impressively durable responses in urothelial bladder cancer (UBC), but the reported response rates warrant improvement. To outline potential strategies to overcome tumor immune resistance, herein, we summarize current models of tumor immunology with a specific focus on bladder cancer. Recognition of tumor-specific antigens through cross-presentation, T cell priming and activation, and trafficking of immune cells to the tumor microenvironment are some of the critical steps we now understand to be necessary for an effective anti-tumor immune response. Many of the involved steps are important targets for therapeutic interventions. As new immunotherapies are developed, predictive biomarkers will also be important to select patients most likely to respond and to better understand tumor biology. Several potential biomarkers are reviewed including PD-L1 expression, identification of T cell-inflamed/non-T cell-inflamed tumors based on immune gene expression, intrinsic molecular subtyping based on luminal/basal or the cancer genome atlas (TCGA) groups, T cell receptor (TCR) sequencing, and somatic mutational density. Within even the past few years our current knowledge of immune biology has exploded, and we are highly optimistic about the future of UBC therapy that will be available to patients.

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“…67 ACT is still in the fairly early stages of testing in bladder cancer, with several ongoing trials, and a new study out of Sweden has just reported a couple highly promising results from a small cohort of individuals with metastatic UCC, including one patient who demonstrated a complete response. 68 More research into optimizing and expanding this technology is needed to assess its potential in UCC patients, and though it is a relatively high cost technology, due to the highly personalized nature of taking each individual patient’s own T-cells for the ex vivo modifications, that is also a large part of what makes it so appealing, at least in concept, in our current world of modern precision medicine.…”

Section: Immunotherapy: Promising New Horizonsmentioning

confidence: 99%

Pharmacogenomics

Jones

Felsenstein

Theodorescu

2016

Urologic Clinics of North America

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The clinical management of bladder cancer has seen little change over the last three decades and there is pressing need to identify more effective treatments for advanced disease. Low clinical utilization of neoadjuvant therapies stems from historical limitations in the ability to predict those patients most likely to respond to combination chemotherapies. Trials with targeted agents in bladder cancer have seen mixed results-possibly due to the lack of enrollment criterion that include molecular and genetic screening and limited knowledge of biomarkers that are predictive of response. Several recent genome-wide characterization studies have demonstrated bladder cancers are a highly heterogeneous set of diseases, comprised of a wide range of genomic and molecular alterations. Novel classification schemes have described new molecular subtypes by which bladder cancers may be grouped and might better predict patient response to various therapies. These findings have provided information about the molecular underpinnings of bladder carcinogenesis and progression and shed light possible reasons why some clinical trials with targeted therapies have failed to see improved patient outcomes. This review will focus on several recent molecular and genetic studies, highlighting promising clinical trials and retrospective studies and discuss emerging trials that utilize predictive biomarkers to match patients with the therapies to which they are most likely to respond. In the coming years, the implementation of predictive genomic and molecular biomarkers will revolutionize the field of urologic oncology and the clinical management bladder cancer.

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Pilot study of adoptive immunotherapy with sentinel node-derived T cells in muscle-invasive urinary bladder cancer

Abstract: Infusion of expanded autologous tumor-specific T lymphocytes is feasible and safe, and objective responses according to RECIST were recorded. One objective responder to immunotherapy displayed notably long overall survival.

Cited by 14 publications

References 34 publications

Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer

Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer

Emerging role of immunotherapy in urothelial carcinoma—Immunobiology/biomarkers

Pharmacogenomics

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