Next-generation immuno-oncology agents: current momentum shifts in cancer immunotherapy

Abstract

Cancer immunotherapy has reached a critical point, now that immune checkpoint inhibitors and two CART products have received market approval in treating 16 types of cancers and 1 tissue-agnostic cancer indication. Accompanying these advances, the 2018 Nobel Prize was awarded for the discovery of immune checkpoint pathways, which has led to the revolution of anti-cancer treatments. However, expanding the indications of immuno-oncology agents and overcoming treatment resistance face mounting challenges. Although combination immunotherapy is an obvious strategy to pursue, the fact that there have been more failures than successes in this effort has served as a wake-up call, placing emphasis on the importance of building a solid scientific foundation for the development of next-generation immuno-oncology (IO) agents. The 2019 China Cancer Immunotherapy Workshop was held to discuss the current challenges and opportunities in IO. At this conference, emerging concepts and strategies for IO development were proposed, focusing squarely on correcting the immunological defects in the tumor microenvironment. New targets such as Siglec-15 and new directions including neoantigens, cancer vaccines, oncolytic viruses, and cytokines were reviewed. Emerging immunotherapies were discussed in the areas of overcoming primary and secondary resistance to existing immune checkpoint inhibitors, activating effector cells, and targeting immunosuppressive mechanisms in the tumor microenvironment. In this article, we highlight old and new waves of IO therapy development, and provide perspectives on the latest momentum shifts in cancer immunotherapy.

Expression signature, prognosis value, and immune characteristics of Siglec-15 identified by pan-cancer analysis

“… 40 However, the anti-tumor effect of a single-agent PD-1 inhibitor is limited, with an effective response rate of less than 30%. 3 , 29 , 41 , 42 Chen et al discovered a close relationship between Siglec-15 and the B7 family by protein sequence analysis. 26 Although several binding partners on tumor cells have been identified for Siglec-15, 43 – 45 the ligand on T cells for Siglec-15 is unclear.…”

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

“…Pembrolizumab is now approved for several other cancer types including non-small cell squamous cell carcinoma, recurrent head and neck squamous cell cancer, and solid cancers with high microsatellite instability (MSI-H) or mismatch repair (MMR) gene defects, including endometrial cancer [22,23]. There are now several other FDA-approved antibodies targeting the PD-1 axis [12,24], many of which are in single and combination therapy clinical trials for ovarian cancer, endometrial cancer, and other malignancies [25,26].…”

Reactive Oxygen Species and Antitumor Immunity—From Surveillance to Evasion

“…Immune checkpoint inhibitors (ICI) and adoptive cell therapy (ACT) are two of the main actors in the immune-oncologic approach aiming at boosting antitumor immunity [ 120 ]. Treatment strategies based on antioxidants exploitation were developed to maintain antitumor activity by ACT under hypoxia and oxidative stress conditions.…”