Anti-PD-1 and PD-L1 Therapy for Bladder Cancer: What is on the Horizon?

Sundararajan, Srinath; Vogelzang, Nicholas J.

doi:10.2217/fon.15.162

Cited by 21 publications

(17 citation statements)

References 47 publications

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“…Tumour cells escape from immunity by upregulating PD‐L1 expression. Therefore, blocking both PD‐1 and PD‐L1 is a strategy to overcome tumour escape . CTLA‐4 (known as CD152) is structurally a CD28 homolog.…”

Section: Immune Checkpoint Inhibitor (Ici) For Treatment Of Bladder Cmentioning

confidence: 99%

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Toll‐like receptors: The role in bladder cancer development, progression and immunotherapy

Moghadam

Nowroozi

2019

Scand J Immunol

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Bladder cancer is one of the leading causes of death worldwide. The main immune mechanisms which lead to bladder cancer development or treatment outcomes have yet to be elucidated. Toll‐like receptors (TLRs) play key roles against cancer. TLRs are expressed both on immune cells and on tumour cells and drive immune responses in progression as well as treatment of cancer. Identification of signalling pathways via TLRs could revolutionize further improvement of therapeutic strategies against cancers in the future. According to the recent studies, TLRs agonists are effective immunostimulants and have important role in induction of immune responses with immunotherapeutic potential against several diseases including cancer. They play an important role in the bladder urothelium as a part of immune defence against uropathogens. On the other hand, decreased TLRs expression was found in bladder tumours, particularly in non‐muscle‐invasive ones. Bacillus Calmette‐Guerin (BCG) (agonist of TLR2 and TLR4) is approved by US FDA for immunotherapy of bladder cancer. Despite high efficiency, immunotherapy with BCG may cause toxicity and adverse effects. Nowadays, in vitro and in vivo studies have been conducted to find alternative options for non‐responder patients. Studies on TLR agonists for bladder cancer treatment have shown promising results. In this review, we discuss recent data about mechanisms played by TLRs in bladder cancer developments as well as therapeutic application of TLR agonists in cancer treatment.

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Section: Immune Checkpoint Inhibitor (Ici) For Treatment Of Bladder Cmentioning

confidence: 99%

“…Therefore, blocking both PD-1 and PD-L1 is a strategy to overcome tumour escape. 143 CTLA-4 (known as CD152) is structurally a CD28 homolog. CD28 is a transmembrane protein expressed on the surface of the T cells that provides co-stimulatory signals and plays a significant role in T cell activation.…”

Section: Inhibitor (Ici) For Treatment Of Bladder Cancermentioning

confidence: 99%

Toll‐like receptors: The role in bladder cancer development, progression and immunotherapy

Moghadam

Nowroozi

2019

Scand J Immunol

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“…The relative success of immune checkpoint inhibition for various metastatic cancers has sparked interest in using these novel treatments for the NMIBC population . Although immune checkpoints normally allow self‐tolerance, tumor cells exploit this regulatory pathway by overexpressing inhibitory immune checkpoint molecules.…”

Section: Salvage Intravesical Therapiesmentioning

confidence: 99%

“…93 The relative success of immune checkpoint inhibition for various metastatic cancers has sparked interest in using these novel treatments for the NMIBC population. 3,94 Although immune checkpoints normally allow self-tolerance, tumor cells exploit this regulatory pathway by overexpressing inhibitory immune checkpoint molecules. Therefore, recent therapies have used monoclonal antibodies to block immune checkpoint receptors (cytotoxic T lymphocyte antigen and programmed death 1) or immune checkpoint ligands (B7 and programmed death ligand 1 [PD-L1]).…”

Section: Emerging Salvage Immunotherapiesmentioning

confidence: 99%

Non–muscle‐invasive bladder cancer: Intravesical treatments beyond Bacille Calmette‐Guérin

Packiam

Johnson

Steinberg

2016

Cancer

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An unmet need exists for patients with high-risk non-muscle-invasive bladder cancer for whom bacille Calmette-Guérin (BCG) has failed and who seek further bladder-sparing approaches. This shortcoming poses difficult management dilemmas. This review explores previously investigated first-line intravesical therapies and discusses emerging second-line treatments for the heterogeneous group of patients for whom BCG has failed. The myriad of recently published and ongoing trials assessing novel salvage intravesical treatments offer promise to patients who both seek an effective cure and want to avoid radical surgery. However, these trials must carefully be contextualized by specific patient, tumor, and recurrence characteristics. As data continue to accumulate, there will potentially be a role for these agents as second-line or even first-line intravesical therapies. Cancer 2017;123:390-400. © 2016 American Cancer Society.

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“…There are also encouraging data from pembrolizumab, with an ORR of 25% (7/28 patients), and avelumab (an IgG1 anti PD-L1 antibody fully capable of ADCC; EMD Serono), with 8/44 patients having a response (18%) and 6/12 patients with ≥ 5% of tumor cells expressing PD-L1 having a response [41]. This has led to multiple ongoing studies with PD-1/PD-L1-targeting agents either alone or in combination with other agents in various stages of urothelial cancer, as recently reviewed [42,43]. …”

Section: Bladder Cancermentioning

confidence: 99%

Immunotherapy in genitourinary malignancies

Wattenberg

Fong

Madan

et al. 2016

Current Opinion in Urology

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Purpose of review Active investigation suggests immune checkpoint inhibitor therapy and therapeutic cancer vaccines provide clinical benefit for genitourinary (GU) malignancies including prostate cancer, renal cell carcinoma (RCC) and bladder cancer. Recent developments in the utility of immune checkpoint inhibitor and vaccine therapy for the management of GU malignancies are highlighted in this review. Recent findings Dramatic responses to checkpoint inhibitor therapy have been demonstrated in RCC and bladder cancer with recent FDA approvals in both indications. No benefit to checkpoint inhibitor therapy has yet been shown for the management of prostate cancer. Therapeutic cancer vaccines have also shown benefit in the treatment of GU malignancies, specifically in the treatment of prostate cancer. Despite advances in these therapeutic modalities, benefit is limited to a subset of patients. Summary Current evidence supports the use of immune checkpoint inhibitor therapy and therapeutic cancer vaccines for the management of GU malignancies. Further development of biomarkers for predicting response and study of combination therapy is required to achieve optimal efficacy with these therapeutic interventions.

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Anti-PD-1 and PD-L1 Therapy for Bladder Cancer: What is on the Horizon?

Cited by 21 publications

References 47 publications

Toll‐like receptors: The role in bladder cancer development, progression and immunotherapy

Toll‐like receptors: The role in bladder cancer development, progression and immunotherapy

Non–muscle‐invasive bladder cancer: Intravesical treatments beyond Bacille Calmette‐Guérin

Immunotherapy in genitourinary malignancies

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