1. Academic Validation
  2. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics

Immune checkpoint inhibitors of PD-L1 as cancer therapeutics

  • J Hematol Oncol. 2019 Sep 5;12(1):92. doi: 10.1186/s13045-019-0779-5.
Akintunde Akinleye 1 Zoaib Rasool 2
Affiliations

Affiliations

  • 1 Department of Internal Medicine, Sovah Health, Danville, VA, 24541, USA. AKINTUNDE.AKINLEYE@LPNT.NET.
  • 2 Department of Internal Medicine, Sovah Health, Danville, VA, 24541, USA.
Abstract

Since the discovery of Immune Checkpoint Proteins, there has been a special interest in developing Antibodies that block programmed cell death 1 receptor (PD-1) and programmed cell death receptor ligand 1 (PD-L1) for a subset of Cancer patients. PD-1 signaling negatively regulates T cell-mediated immune responses and serves as a mechanism for tumors to evade an antigen-specific T cell immunologic response. It plays a role in promoting Cancer development and progression by enhancing tumor cell survival. With this background, PD-1 signaling represents a valuable therapeutic target for novel and effective Cancer Immunotherapy. Clinical data shows that blockade of this PD-1 signaling significantly enhance antitumor immunity, produce durable clinical responses, and prolong survival. Currently, there are three FDA-approved PD-L1 inhibitors for various malignancies ranging from non-small cell lung Cancer to Merkel cell carcinoma. This review is to summarize many ongoing phase II/III trials of atezolizumab, durvalumab, avelumab, and new PD-L1 inhibitors in clinical developments. In particular, we focus on key trials that paved the pathway to FDA-approved indications for atezolizumab, durvalumab, and avelumab. Despite the popularity and accelerated FDA approval of PD-L1 inhibitors, further considerations into predictive biomarkers, mechanisms of resistance, treatment duration, immune-related toxicities, and PD-L1 expression threshold are needed to optimize Anticancer potential in this class of immunotherapy.

Keywords

Companion diagnostics assays; Immune checkpoints; Merkel cell carcinoma; Non-small cell lung cancer; T cell dysfunction; Tumor-infiltrating lymphocytes.

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