Dear JITC Readers,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
To view the entire February 2019 JITC Digest, please click here.
