These treatments often fail, resulting in tumor metastasis and recurrence. Therefore, there is a critical need for novel cancer therapies. In recent years, an increasing number of studies have revealed that immune responses play a critical role in conventional cancer therapies. Replication-selective oncolytic viruses are a rapidly expanding therapeutic platform for cancer.
Professor Wang Shengdian and his group from the Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, have studied tumor immunity for several years, with a team focusing on oncolytic adenovirus. In this work, entitled "CD8+ T cell response mediates the therapeutic effects of oncolytic adenovirus in an immunocompetent mouse model", published in Chinese Science Bulletin 2012, Vol. 57(1), this team has demonstrated that the host anti-tumor immune responses, especially the CD8+ T cell responses, play a critical role in the therapeutic effects of oncolytic adenovirus. These studies might shed light on novel cancer therapies.
Researchers have identified several oncolytic viruses such as poliovirus, adenovirus, vesicular stomatitis virus, reovirus, and vaccinia virus, which can selectively infect or replicate in cancer cells, but spare normal cells. Among these, adenovirus has been the most commonly used oncolytic virus in the last decade, because of its efficacy, safety, and ease of manipulation. When administered to tumors, oncolytic adenovirus infects and kills cancer cells as a result of the normal viral life cycle, by replicating in cells and releasing progeny viruses. However, adenoviral infection is immunogenic and can induce strong anti-viral immune responses, which accelerate the clearance of virus and limit the therapeutic effects on cancer. Some studies have shown that suppressing the immune system could enhance the efficacy of oncolytic vectors. On the other hand, recent preclinical and clinical studies have suggested that the immune response plays an important role in mediating the antitumor efficacy. Therefore, the influence of immune responses on oncolytic therapy is complex. Because of the species specificity of adenoviral replication, it was widely assumed that adenoviral replication would not occur in mouse tumors.
Consequently, oncolytic adenoviral vectors have been commonly evaluated in immunodeficient mouse-human tumor xenograft models, which do not accurately reflect what happens in humans treated with oncolytic adenovirus. A team led by Professor Yaohe Wang from the Center for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, previously screened a panel of mouse tumor cell lines and identified two cell lines—CMT 93 (a murine rectal cancer cell line) and CMT64 (a murine non-small-cell lung cancer cell line) with significant permissibility for adenoviral gene expression, cytopathic effects, and/or replication.
In this work, the team lead by Professor Wang Shengdian evaluated the roles of immune components in oncolytic adenoviral therapy with a murine tumor by subcutaneously inoculating CMT 93 cells into syngeneic C57BL/6 mice. They found that CD8+ T cells, but not CD4+ T cells or natural killer cells, are critical mediators of the antitumor efficacy of oncolytic adenovirus by deletion of the corresponding cell subsets with specific antibodies. Intratumoral injection of adenovirus serotype 5 (Ad5) could induce intensive infiltration of CD8+ T cells into the tumor, and increase tumor-specific interferon-ã production and cytotoxic T lymphocyte activity. The anti-tumor T cell responses induced by Ad5 therapy produced long-term tumor-specific memory immune responses that protected the cured mice well from tumor rechallenge. This anti-tumor immune memory is thought to play a major role in preventing tumor relapse. For larger tumors, Ad5 therapy alone controls tumor growth only transiently. However, Ad5 therapy followed by treatment with agonistic anti-4-1BB (cluster differentiation 137, CD137) antibody, a potent enhancer of the specific CD8+ T cell response, resulted in complete rejection of all transplanted tumors, demonstrating that promotion of T cell responses against tumors could enhance the therapeutic effects of oncolytic adenovirus.
In summary, this study provides insight into the antitumor mechanisms of oncolytic adenovirus, in addition to their direct oncolytic effect. Meanwhile, this study proposes a new and more effective therapeutic regime for cancer treatment using a combination therapy of oncolytic adenovirus and immunotherapy.
See the article: YANG Y J, LI X Z, WANG Y H, WANG S D. CD8+ T cell response mediates the therapeutic effects of oncolytic adenovirus in an immunocompetent mouse model. Chinese Science Bulletin 2012 Vol. 57(1): 48-53.
Wang Shengdian | EurekAlert!
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Life Sciences
28.03.2017 | Information Technology
28.03.2017 | Physics and Astronomy