An ideal generic cancer immunotherapy should mobilize the immune system to destroy tumor cells without harming healthy cells and remain active in case of recurrence. Furthermore, it should preferably not rely on tumor-specific surface markers, as these are only available in a limited set of malignancies. Despite approval for treatment of various cancers, clinical application of cytokines is still impeded by their multiple toxic side effects. Type I IFN has a long history in the treatment of cancer, but its multifaceted activity pattern and complex side effects prevent its clinical use. Here we develop AcTakines (Activity-on-Target cytokines), optimized (mutated) immunocytokines that are up to 1,000-fold more potent on target cells, allowing specific signaling in selected cell types only. Type I IFN-derived AcTaferon (AFN)-targeting Clec9A+ dendritic cells (DC) displayed strong antitumor activity in murine melanoma, breast carcinoma, and lymphoma models and against human lymphoma in humanized mice without any detectable toxic side effects. Combined with immune checkpoint blockade, chemotherapy, or low-dose TNF, complete tumor regression and long-lasting tumor immunity were observed, still without adverse effects. Our findings indicate that DC-targeted AFNs provide a novel class of highly efficient, safe, and broad-spectrum off-the-shelf cancer immunotherapeutics with no need for a tumor marker.Significance: Targeted type I interferon elicits powerful antitumor efficacy, similar to wild-type IFN, but without any toxic side effects. Cancer Res; 78(2); 463–74. ©2017 AACR.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2DBGV0A
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
-
Cover letters are attached to your resume when you apply for a job. The purpose of cover letters is to persuade the employer that you are we...
-
2016-12-10T02-17-59Z Source: Indo American Journal of Pharmaceutical Research Radha S & Sreelatha .S*. Research has demonstrated th...
-
ACS Nano DOI: 10.1021/acsnano.7b01783 from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2trY7nv via...
-
Need Industrial relations advice? Unfair dismissals laws? Discrimination in the workplace? Sexual harassment? We can help. AWNA is Australia...
-
Participant Experiences of Attending a Community CBT Workshop for Insomnia: A Qualitative Six-Year Follow-Up. Behav Sleep Med. 2017 Ap...
-
Persuasive speech ideas - 50+ provoking, fresh ideas to help you find the persuasive speech topic best suited to you and your audience. fr...
-
Description A Caucasian boy aged 5 years presented with acute onset of a non-tender, palpable purpuric rash to his lower limbs, preceded by ...
-
Publication date: Available online 10 February 2017 Source: Brachytherapy Author(s): M.F. Jamaluddin, S. Ghosh, M.P. Waine, M. Tavakoli, J...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου