JITC Digest February 2019

jitc-logo.gif

Inside this Issue:

Letter from the Editor

Dear JITC Readers,pedro-romero_1__1_.jpg

In the February edition of the JITC Digest, there are four articles of note of which I would like to highlight. First, the article “EnanDIM - a novel family of L-nucleotide-protected TLR9 agonists for cancer immunotherapy,” by Kerstin Kapp et al. reports the development of EnanDIM® molecules, a novel family of chemically defined TLR9 agonists with the ability to activate the innate and adaptive immune systems and elicit potent anti-tumor responses without generating off-target effects. The described immunological features of EnanDIM® molecules in this study suggest the potential for combination with other immunotherapeutic approaches and prompts the need for further preclinical and clinical development.

Next, the research article, “Tumor microenvironment modulation enhances immunologic benefit of chemoradiotherapy,” by Aurelie Hanoteau et al. investigated clinically relevant in vivo models combining chemoradiotherapy (CRT) with two immunomodulatory drugs: cyclophosphamide (CTX) and L-n6-(1-iminoethyl)-lysine (L-NIL). Results demonstrated that alteration of the tumor immune microenvironment can render refractory tumors susceptible to CRT and suggests the potential for clinical translation of this approach.

Furthermore, the article, “Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial,” by Ulrich Keilholz et al. presents safety and efficacy data from previously treated patients with locally advanced or metastatic melanoma enrolled in the phase 1b, dose-expansion part of the JAVELIN Solid Tumor trial. Avelumab demonstrated durable responses and an acceptable safety profile, as well as encouraging efficacy for patients with PD-L1–positive tumors and those who had progressed after ipilimumab therapy.

Finally, Jana de Sostoa et al.’s article, “Targeting the tumor stroma with an oncolytic adenovirus secreting a fibroblast activation protein-targeted bispecific T-cell engager,” details a novel strategy to minimize the antiviral immune response needed to target cancer calls and fibroblast activation protein-alpha (FAP). By inserting a bispecific T-cell Engager (FBiTE) targeting FAP into the oncolytic adenovirus, ICOVIR15K, Sostoa’s group developed an FBiTE-armed adenovirus (ICO15K-FBiTE) shown to enhance viral spread and overall anti-tumor efficacy without increasing clinical toxicity. Similar results with a similar FAP-BiTE were reported by an Oxford-based group using the oncolytic group B adenovirus enadenotucirev (Freedman JD et al. Cancer Res Dec 15, 2018).

Additionally, I welcome you all to enjoy a new feature through SITC Connect where JITC editors share a monthly reading list of publications of interest elsewhere in the field that add value to what readers can find in JITC. Check out the first edition of “JITC’s Reading List” and stay tuned for new content from each month’s featured editor.

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


JITC Editor Picks

Targeting the tumor stroma with an oncolytic adenovirus secreting a fibroblast activation protein-targeted bispecific T-cell engager

Jana de Sostoa, Carlos Alberto Fajardo, Rafael Moreno, Maria D. Ramos, Martí Farrera-Sal and Ramon Alemany
Journal for ImmunoTherapy of Cancer, 7:19 (25 January 2019)
Research Article

Summary:

Despite the potential of oncolytic viruses (OVs) as promising anti-tumor agents, there exist several obstacles to successful implementation of oncolytic therapy including a limited antiviral immune response by the host as well as the presence of stroma in tumors, producing a physical barrier to oncolytic adenovirus (OAd) spread in addition to enhanced cancer cell survival phenotypes, an immunosuppressive environment and resistance to therapy. Sostoa et al. presents a novel strategy to minimize the necessary antiviral immune response without increasing clinical toxicity through inserting a bispecific T-cell Engager (FBiTE) targeting the fibroblast activation protein-alpha (FAP) into the oncolytic adenovirus, ICOVIR15K, for the development of a FBiTE-armed adenovirus (ICO15K-FBiTE). This study comes in the JITC’s February issue independently of another study with a similar FAP-BiTE reported by an Oxford-based group using the oncolytic group B adenovirus enadenotucirev a month ago in Cancer Research (Freedman JD et al. Cancer Res Dec 15, 2018).

Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial

Ulrich Keilholz, Janice M. Mehnert, Sebastian Bauer, Hugues Bourgeois, Manish R. Patel, Donald Gravenor, John J. Nemunaitis, Matthew H. Taylor, Lucjan Wyrwicz, Keun-Wook Lee, Vijay Kasturi, Kevin Chin, Anja von Heydebreck and James L. Gulley
Journal for ImmunoTherapy of Cancer, 7:12 (16 January 2019)
Research Article

Summary:

Avelumab is currently FDA approved for treatment of patients with metastatic Merkel cell carcinoma and previously treated patients with locally advanced or metastatic urothelial carcinoma. Keilholz et al. reports safety and efficacy data investigating the use of avelumab in previously treated patients with unresectable, locally advanced or metastatic melanoma enrolled in the phase 1b, dose-expansion cohort of the JAVELIN Solid Tumor trial (NCT01772004). Consistent with results from larger pivotal studies of checkpoint inhibitors for second-line or later treatment of advanced melanoma, avelumab demonstrated durable responses and an acceptable safety profile, as well as encouraging efficacy for patients with PD-L1–positive tumors and those who had progressed after ipilimumab therapy.

Tumor microenvironment modulation enhances immunologic benefit of chemoradiotherapy

Aurelie Hanoteau, Jared M. Newton, Rosemarie Krupar, Chen Huang, Hsuan-Chen Liu, Angelina Gaspero, Robyn D. Gartrell, Yvonne M. Saenger, Thomas D. Hart, Saskia J. Santegoets, Damya Laoui, Chad Spanos, Falguni Parikh, Padmini Jayaraman, Bing Zhang, Sjoerd H. Van der Burg, Jo A. Van Ginderachter, Cornelis J. M. Melief and Andrew G. Sikora
Journal for ImmunoTherapy of Cancer, 7:10 (15 January 2019)
Research Article

Summary:

Chemoradiotherapy (CRT) is a highly effective standard of care cancer treatment for the majority of patients with HPV-associated squamous cell carcinoma of the head and neck (HNSCC). However, in patients with locoregionally advanced, and recurrent or metastatic disease, CRT has high failure rates, suggestive of coinciding pro- and anti-tumoral immune responses. To block potential immunosuppressive mechanisms, Hanoteau et al. investigated in vivo models comparing immune responses induced by CRT alone and in conjunction with two immunomodulatory drugs: cyclophosphamide (CTX) and L-n6-(1-iminoethyl)-lysine (L-NIL), an inducible nitric oxide synthase inhibitor. Results suggest that the combination of CTX with L-NIL may re-condition the tumor immune microenvironment, enhancing immunologic benefit and improving treatment efficacy of CRT.

EnanDIM - a novel family of L-nucleotide-protected TLR9 agonists for cancer immunotherapy

Kerstin Kapp, Barbara Volz, Michael A. Curran, Detlef Oswald, Burghardt Wittig and Manuel Schmidt
Journal for ImmunoTherapy of Cancer, 7:5 (8 January 2019)
Research Article

Summary:

An activator of both the adaptive and innate immune response, toll-like receptor 9 (TLR9) has previously been shown to re-activate immune surveillance to effectively recognize tumor-specific antigens on cancer cells of tumor patients but with off-target effects due to chemical modifications to the molecular composition. In the present study, Kapp et al. presented the development of EnanDIM® molecules, a novel family of L-nucleotide-protected and stabilized TLR9 agonists lacking previous chemical modifications, which appear apt to deliver a wide therapeutic window of anti-tumor effects including tumor microenvironment modulation, inhibition of tumor growth and production of enduring tumor-specific memory.

Complete response of metastatic melanoma in a patient with Crohn’s disease simultaneously receiving anti-α4β7 and anti-PD1 antibodies

Christopher C. Frohne, Ernesto M. Llano, Ashley Perkovic, Russell D. Cohen and Jason J. Luke
Journal for ImmunoTherapy of Cancer, 7:2 (6 January 2019)
Case Report

Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single-center experience

Omar Mamlouk, Umut Selamet, Shana Machado, Maen Abdelrahim, William F. Glass, Amanda Tchakarov, Lillian Gaber, Amit Lahoti, Biruh Workeneh, Sheldon Chen, Jamie Lin, Noha Abdel-Wahab, Jean Tayar, Huifang Lu, Maria Suarez-Almazor, Nizar Tannir, Cassian Yee, Adi Diab and Ala Abudayyeh
Journal for ImmunoTherapy of Cancer, 7:2 (6 January 2019)
Short Report

Nature of coexisting thyroid autoimmune disease determines success or failure of tumor immunity in thyroid cancer

Shahnawaz Imam, Pervaiz Dar, Rodis Paparodis, Khalil Almotah, Ahmed Al-Khudhair, Syed Abdul-Moiz Hasan, Nancy Salim and Juan Carlos Jaume
Journal for ImmunoTherapy of Cancer, 7:3 (7 January 2019)
Research Article

Cutaneous adverse reactions in B-RAF positive metastatic melanoma following sequential treatment with B-RAF/MEK inhibitors and immune checkpoint blockade or vice versa. A single-institutional case-series

Abdul Rafeh Naqash, Danielle M. File, Carolyn M. Ziemer, Young E. Whang, Paula Landman, Paul B. Googe and Frances A. Collichio
Journal for ImmunoTherapy of Cancer, 7:4 (8 January 2019)
Case Report

A rare population of tumor antigen-specific CD4+CD8+ double-positive alpha-beta T lymphocytes uniquely provide CD8-independent TCR genes for engineering therapeutic T cells

Junko Matsuzaki, Takemasa Tsuji, Thinle Chodon, Courtney Ryan, Richard C. Koya and Kunle Odunsi
Journal for ImmunoTherapy of Cancer, 7:7 (9 January 2019)
Research Article

Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics

Zong Sheng Guo, Binfeng Lu, Zongbi Guo, Esther Giehl, Mathilde Feist, Enyong Dai, Weilin Liu, Walter J. Storkus, Yukai He, Zuqiang Liu and David L. Bartlett
Journal for ImmunoTherapy of Cancer, 7:6 (9 January 2019)
Review

Chemo-immunotherapy improves long-term survival in a preclinical model of MMR-D-related cancer

Claudia Maletzki, Leonie Wiegele, Ingy Nassar, Jan Stenzel and Christian Junghanss
Journal for ImmunoTherapy of Cancer, 7:8 (10 January 2019)
Research Article

Chimeric tumor modeling reveals role of partial PD-L1 expression in resistance to virally induced immunotherapy

Mee Y. Bartee, Parker C. Dryja and Eric Bartee
Journal for ImmunoTherapy of Cancer, 7:11 (16 January 2019)
Short Report

Hyperspectral cell sociology reveals spatial tumor-immune cell interactions associated with lung cancer recurrence

Katey S. S. Enfield, Spencer D. Martin, Erin A. Marshall, Sonia H. Y. Kung, Paul Gallagher, Katy Milne, Zhaoyang Chen, Brad H. Nelson, Stephen Lam, John C. English, Calum E. MacAulay, Wan L. Lam and Martial Guillaud
Journal for ImmunoTherapy of Cancer, 7:13 (16 January 2019)
Research Article

Tbet-positive regulatory T cells accumulate in oropharyngeal cancers with ongoing tumor-specific type 1 T cell responses

S. J. Santegoets, C. L. Duurland, E. S. Jordanova, J. J. van Ham, I. Ehsan, S. L. van Egmond, M. J. P. Welters and S. H. van der Burg
Journal for ImmunoTherapy of Cancer, 7:14 (18 January 2019)
Research Article

A novel anti-HER2 anthracycline-based antibody-drug conjugate induces adaptive anti-tumor immunity and potentiates PD-1 blockade in breast cancer

Lucia D’Amico, Ulrike Menzel, Michael Prummer, Philipp Müller, Mélanie Buchi, Abhishek Kashyap, Ulrike Haessler, Alexander Yermanos, Rémy Gébleux, Manfred Briendl, Tamara Hell, Fabian I. Wolter, Roger R. Beerli, Iva Truxova, Špíšek Radek, Tatjana Vlajnic, Ulf Grawunder, Sai Reddy and Alfred Zippelius
Journal for ImmunoTherapy of Cancer, 7:16 (21 January 2019)
Research Article

A gene expression assay for simultaneous measurement of microsatellite instability and anti-tumor immune activity

Patrick Danaher, Sarah Warren, SuFey Ong, Nathan Elliott, Alessandra Cesano and Sean Ferree
Journal for ImmunoTherapy of Cancer, 7:15 (21 January 2019)
Research Article

Human double negative T cells target lung cancer via ligand-dependent mechanisms that can be enhanced by IL-15

Junlin Yao, Dalam Ly, Dzana Dervovic, Linan Fang, Jong Bok Lee, Hyeonjeong Kang, Yu-Hui Wang, Nhu-An Pham, Hongming Pan, Ming-Sound Tsao and Li Zhang
Journal for ImmunoTherapy of Cancer, 7:17 (22 January 2019)
Research Article

Next generation sequencing of PD-L1 for predicting response to immune checkpoint inhibitors

Jeffrey M. Conroy, Sarabjot Pabla, Mary K. Nesline, Sean T. Glenn, Antonios Papanicolau-Sengos, Blake Burgher, Jonathan Andreas, Vincent Giamo, Yirong Wang, Felicia L. Lenzo, Wiam Bshara, Maya Khalil, Grace K. Dy, Katherine G. Madden, Keisuke Shirai, Konstantin Dragnev, Laura J. Tafe, Jason Zhu, Matthew Labriola, Daniele Marin, Shannon J. McCall, Jeffrey Clarke, Daniel J. George, Tian Zhang, Matthew Zibelman, Pooja Ghatalia, Isabel Araujo-Fernandez, Luis de la Cruz-Merino, Arun Singavi, Ben George, Alexander C. MacKinnon, Jonathan Thompson, Rajbir Singh, Robin Jacob, Deepa Kasuganti, Neel Shah, Roger Day, Lorenzo Galluzzi, Mark Gardner and Carl Morrison
Journal for ImmunoTherapy of Cancer, 7:18 (24 January 2019)
Research Article

A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE)

Jean-Pascal Machiels, Ramon Salazar, Sylvie Rottey, Ignacio Duran, Luc Dirix, Karen Geboes, Christine Wilkinson-Blanc, Gillian Pover, Simon Alvis, Brian Champion, Kerry Fisher, Hilary McElwaine-Johnn, John Beadle and Emiliano Calvo
Journal for ImmunoTherapy of Cancer, 7:20 (28 January 2019)
Research Article

17p deletion strongly influences rituximab elimination in chronic lymphocytic leukemia

Cristina Bagacean, Adrian Tempescul, David Ternant, Anne Banet, Nathalie Douet-Guilbert, Anne Bordron, Boutahar Bendaoud, Hussam Saad, Mihnea Zdrenghea, Christian Berthou, Gilles Paintaud and Yves Renaudineau
Journal for ImmunoTherapy of Cancer, 7:22 (29 January 2019)
Short Report

Combined treatment with HMGN1 and anti-CD4 depleting antibody reverses T cell exhaustion and exerts robust anti-tumor effects in mice

Chang-Yu Chen, Satoshi Ueha, Yoshiro Ishiwata, Shoji Yokochi, De Yang, Joost J. Oppenheim, Haru Ogiwara, Shigeyuki Shichino, Shungo Deshimaru, Francis H. W. Shand, Shiro Shibayama and Kouji Matsushima
Journal for ImmunoTherapy of Cancer, 7:21 (29 January 2019)
Research Article

FLT PET/CT imaging of metastatic prostate cancer patients treated with pTVG-HP DNA vaccine and pembrolizumab

Matthew Scarpelli, Christopher Zahm, Scott Perlman, Douglas G. McNeel, Robert Jeraj and Glenn Liu
Journal for ImmunoTherapy of Cancer, 7:23 (30 January 2019)
Research Article

Clinicopathological and molecular features of responders to nivolumab for patients with advanced gastric cancer

Saori Mishima, Akihito Kawazoe, Yoshiaki Nakamura, Akinori Sasaki, Daisuke Kotani, Yasutoshi Kuboki, Hideaki Bando, Takashi Kojima, Toshihiko Doi, Atsushi Ohtsu, Takayuki Yoshino, Takeshi Kuwata, Akihito Tsuji and Kohei Shitara
Journal for ImmunoTherapy of Cancer, 7:24 (31 January 2019)
Research Article

Demarcated thresholds of tumor-specific CD8 T cells elicited by MCMV-based vaccine vectors provide robust correlates of protection

Elham Beyranvand Nejad, Robert B. Ratts, Eleni Panagioti, Christine Meyer, Jennifer D. Oduro, Luka Cicin-Sain, Klaus Früh, Sjoerd H. van der Burg and Ramon Arens
Journal for ImmunoTherapy of Cancer, 7:25 (31 January 2019)
Research Article

Two roads for oncolytic immunotherapy development

Howard L. Kaufman and Praveen K. Bommareddy
Journal for ImmunoTherapy of Cancer, 7:26 (1 February 2019)
Commentary

Proliferative potential and resistance to immune checkpoint blockade in lung cancer patients

Sarabjot Pabla, Jeffrey M. Conroy, Mary K. Nesline, Sean T. Glenn, Antonios Papanicolau-Sengos, Blake Burgher, Jacob Hagen, Vincent Giamo, Jonathan Andreas, Felicia L. Lenzo, Wang Yirong, Grace K. Dy, Edwin Yau, Amy Early, Hongbin Chen, Wiam Bshara, Katherine G. Madden, Keisuke Shirai, Konstantin Dragnev, Laura J. Tafe, Daniele Marin, Jason Zhu, Jeff Clarke, Matthew Labriola, Shannon McCall, Tian Zhang, Matthew Zibelman, Pooja Ghatalia, Isabel Araujo-Fernandez, Arun Singavi, Ben George, Andrew Craig MacKinnon, Jonathan Thompson, Rajbir Singh, Robin Jacob, Lynn Dressler, Mark Steciuk, Oliver Binns, Deepa Kasuganti, Neel Shah, Marc Ernstoff, Kunle Odunsi, Razelle Kurzrock, Mark Gardner, Lorenzo Galluzzi and Carl Morrison
Journal for ImmunoTherapy of Cancer, 7:27 (1 February2019)
Research Article

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.