JITC Digest January 2019

By JITC Publications posted 01-23-2019 00:00

Like

INSIDE THIS ISSUE:

LETTER FROM THE EDITOR JITC EDITOR PICKS OTHER RECENT JITC ARTICLES

Letter from the Editor

Dear JITC Readers,

In the January edition of the JITC Digest, there are four noteworthy articles of which I would like to draw special attention. First, the article “Novel TLR2-binding adjuvant induces enhanced T cell responses and tumor eradication,” by Gijs G. Zom et al. reports novel murine data demonstrating the enhanced immunological potency of the novel TLR2-ligand, Amplivant (AV), as an adjuvant in cancer immunotherapy. Such results lay the foundation for further clinical testing of AV-synthetic long peptide (SLP) conjugates.

Next, the research article, “1-Pyrroline-5-carboxylate released by prostate Cancer cell inhibit T cell proliferation and function by targeting SHP1/cytochrome c oxidoreductase/ROS Axis,” by Yutao Yan et al. establishes a crucial immunosuppressive mechanism utilized in prostate cancer by which metabolites released by prostate cancer cells directly impair T cell immunity and anti-tumor functionality.

Furthermore, the article, “Agonist redirected checkpoint, PD1-Fc-OX40L, for cancer immunotherapy,” by George Fromm et al. details the development and characterization of Agonist Redirected Checkpoint™ (ARC), a dual-sided Fc fusion protein platform for the linking of specific checkpoint and costimulatory pathways. Fromm’s group specifically reports on the anti-tumor response and potential therapeutic activity of the prototype ARC molecule, PD1-Fc-OX40L, for both human and mouse.

Finally, Larissa S. Carnevalli et al.’s article, “PI3K-alpha/delta inhibition promotes anti-tumor immunity through direct enhancement of effector CD8+ T-cell activity,” examines the immune response elicited by AZD8835, a dual PI3K-alpha/delta inhibitor, through preclinical syngeneic tumor models and determines how differential dosing of the inhibitor affects anti-tumor immunity through interactions with the tumor immune microenvironment.

With best regards,
Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer

JITC Editor Picks

NOVEL TLR2-BINDING ADJUVANT INDUCES ENHANCED T CELL RESPONSES AND TUMOR ERADICATION

Gijs G. Zom, Marian M. J. H. P. Willems, Selina Khan, Tetje C. van der Sluis, Jan Willem Kleinovink, Marcel G. M. Camps, Gijsbert A. van der Marel, Dmitri V. Filippov, Cornelis J. M. Melief and Ferry Ossendorp
Journal for ImmunoTherapy of Cancer, 6:146 (12 December 2018)
Research Article

Summary:

Previous studies demonstrate the immune activating properties of covalently conjugating the TLR2-ligand, PAM3CSK4, to synthetic long peptides (SLPs) for use as cancer vaccines. The present study shows the enhanced immunological potency of the novel TLR2-ligand, Amplivant (AV), as an adjuvant in cancer immunotherapy. AV conjugated to an SLP enhanced not only activation of dendritic cells in vitro but also induced stronger in vivo T cell priming compared to Pam3CSK4 (the reference TLR2-ligand) conjugated to the same SLP, suggesting the strong therapeutic potential of AV as a TLR2-ligand and justification for further clinical testing of AV-SLP conjugates.

1-PYRROLINE-5-CARBOXYLATE RELEASED BY PROSTATE CANCER CELL INHIBIT T CELL PROLIFERATION AND FUNCTION BY TARGETING SHP1/CYTOCHROME C OXIDOREDUCTASE/ROS AXIS

Yutao Yan, Lei Chang, Hongzhe Tian, Lu Wang, Yawei Zhang, Tao Yang, Guohao Li, Weifeng Hu, Kavita Shah, Gang Chen and Yonglian Guo
Journal for ImmunoTherapy of Cancer, 6:148 (13 December 2018)
Research Article

Summary:

This study by Yutao Yan et al. links prostate cancer cell (PCC) metabolites with T cell proliferation and function through in vitro analysis of PCC conditioned media followed by a metabolomics study using liquid chromatography mass spectroscopy (LC/MS-MS). A crucial immunosuppressive mechanism in prostate cancer was elucidated by which metabolites released by PCC directly impair T cell immunity and anti-tumor functionality through enhancing levels of 1-Pyrroline-5-carboxylate (P5C), subsequently upregulating SHP1, and increasing the levels of reactive oxygen species. Such results suggest a possibly novel target for T cell reactivation in treating prostate cancer.

AGONIST REDIRECTED CHECKPOINT, PD1-FC-OX40L, FOR CANCER IMMUNOTHERAPY

George Fromm, Suresh de Silva, Kellsey Johannes, Arpita Patel, Josiah C. Hornblower and Taylor H. Schreiber
Journal for ImmunoTherapy of Cancer, 6:149 (18 December 2018)
Research Article

Summary:

This article by George Fromm et al. details the development and characterization of Agonist Redirected Checkpoint™ (ARC), a dual-sided Fc fusion protein platform. The prototype ARC molecule (PD1-Fc-OX40L) activated primary human T cells in vitro by increasing effector cytokine production and proliferation, triggered NFkB signaling, and outperformed clinical-stage antibodies (pembrolizumab, nivolumab, tavolixizumab) in stimulating IL-2 secretion. Originally, developed to both block immune checkpoint pathways and activate TNF receptors, ARC has demonstrated the ability to bind PD-L1 and OX40 simultaneously, and appears apt to facilitate a potent anti-tumor polyfunctional T cell response.

PI3K-ALPHA/DELTA INHIBITION PROMOTES ANTI-TUMOR IMMUNITY THROUGH DIRECT ENHANCEMENT OF EFFECTOR CD8+ T-CELL ACTIVITY

Larissa S. Carnevalli, Charles Sinclair, Molly A. Taylor, Pablo Morentin Gutierrez, Sophie Langdon, Anna M. L. Coenen-Stass, Lorraine Mooney, Adina Hughes, Laura Jarvis, Anna Staniszewska, Claire Crafter, Ben Sidders, Elizabeth Hardaker, Kevin Hudson and Simon T. Barry
Journal for ImmunoTherapy of Cancer, 6:158 (27 December 2018)
Research Article

Summary:

Inhibitors of PI3K promote activation of T cell responses through suppression of regulatory T cells or myeloid-derived suppressor cells, leading to enhanced T cell–mediated anti-tumor activity. Carnevalli et al. examined this PI3K-associated immune response through differential dosing of AZD8835, a dual PI3K-alpha/delta inhibitor, in preclinical syngeneic tumor models. Initially developed to treat solid cancers dependent on PI3K-alpha/delta signaling, this study demonstrates a clear role for AZD8835 in potentiating anti-tumor immunity and as a positive modulator of the tumor immune microenvironment in a clinically relevant framework.

SITC Members Receive 60 Percent Submission Discount in 2019

*As a way to thank the SITC members who work tirelessly to advance the science and improve the lives of cancer patients, SITC will provide SITC members with a 60 percent discount on processing fees for all JITC articles accepted in 2019. To take advantage of this SITC member benefit, authors must contact JITC Managing Editor Andrea Kunz at JITCEditor@sitcancer.org or 1-414-271-2456 prior to submission to obtain a discount code and instructions.

Become a SITC member today!

0 comments

0 views

Permalink

https://www.sitcancer.org/blogs/jitc-publications/2019/01/23/jitc-digest-january-2019

Blogs