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Anti-tumor vaccines

Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
October 15, 2016: EBioMedicine
J Chee, B W S R Robinson, R A Holt, J Creaney
Harnessing the immune system to fight cancer is an exciting advancement in lung cancer therapy. Anti-tumor immunity can be augmented by checkpoint blockade therapy, which removes the inhibition/brakes imposed on the immune system by the tumor. Checkpoint blockade therapy with anti-PD1/anti-PDL1 antibodies causes tumor regression in around 25% of lung cancer patients. In another approach, the immune system is forced or accelerated to attack the tumour, via augmentation of the anti-tumour response against mutations carried by each lung tumour...
October 18, 2016: Chest
Erika Heninger, Timothy E G Krueger, Stephanie M Thiede, Jamie M Sperger, Brianna L Byers, Madison R Kircher, David Kosoff, Bing Yang, David F Jarrard, Douglas G McNeel, Joshua M Lang
Immune tolerance to self-antigens can limit robust anti-tumor immune responses in the use of tumor vaccines. Expression of novel tumor associated antigens can improve immune recognition and lysis of tumor cells. The cancer-testis antigen (CTA) family of proteins has been hypothesized to be an ideal class of antigens due to tumor-restricted expression, a subset of which have been found to induce antibody responses in patients with prostate disease. We demonstrate that CTA expression is highly inducible in five different Prostate Cancer (PC) cell lines using a hypomethylating agent 5-Aza-2'-deoxycytidine (5AZA) and/or a histone deacetylase inhibitor LBH589...
October 17, 2016: Oncotarget
Nadia F Nocera, M Catherine Lee, Lucy M De La Cruz, Cinthia Rosemblit, Brian J Czerniecki
The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy...
2016: Frontiers in Pharmacology
Uhi Toh, Shuko Saku, Mina Okabe, Nobutaka Iwakuma, Yuko Kimitsuki, Momoko Akashi, Etsuyo Ogo, Akira Yamada, Shigeki Shichijo, Kyogo Itoh, Yoshito Akagi
Our previous phase II clinical trial showed that therapeutically selected personalized peptide vaccines(PPVs)were effective at boosting anticancer immunity; the immune response after PPV was associated with a clinical outcome as a prognostic factor for metastatic breast cancer(mBC). We conducted an early phase II study to evaluate the safety and efficacy of a new regimen using multiple peptide vaccines(KRM-19)for patients with metastatictriple -negative breast cancer. KRM-19 consisted of 19 mixed peptides chosen from the previously reported 31 PPVs according to their anti-tumor immunologiceffec ts and safety profiles for patients with mBC...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Behjatolah Monzavi-Karbassi, Fariba Jousheghany, Thomas Kieber-Emmons
Development of cancer vaccines targeting tumor-associated antigens (TAAs) is an alternative approach to chemotherapy with sustained anti-tumor effects. The success of active immunotherapy has been hampered by tumor-induced immune suppressors. Regulatory T cells (Tregs) are a population of immune suppressors with a proven role in regulating anti-tumor immune responses. Removing or subduing Tregs activity leads to more robust anti-tumor immune responses. Here, we used a cell-based vaccination strategy in the 4T1 murine mammary model to examine whether bulk removal of certain TAAs, using their glycan profile, can affect the immunogenicity of the vaccine...
October 19, 2016: Immunological Investigations
Mladen Korbelik, Judith Banáth, Wei Zhang
Myeloid regulatory cells (Mregs) are, together with regulatory T cells (Tregs), a dominant effector population responsible for restriction of the duration and strength of antitumor immune response. Photodynamic therapy (PDT) and cancer vaccines generated by PDT are modalities whose effectiveness in tumor destruction is closely dependent on the associated antitumor immune response. The present study investigated whether the immunodepletion of granulocytic Mregs in host mice by anti-GR1 antibody would improve the response of tumors to PDT or PDT vaccines in these animals...
October 15, 2016: Cancers
Rebecca S Abraham, Duane A Mitchell
Dendritic cell (DC) vaccines are an immunotherapeutic approach to cancer treatment that use the antigen-presentation machinery of DCs to activate an endogenous anti-tumor response. In this treatment strategy, DCs are cultured ex vivo, exposed to tumor antigens and administered to the patient. The ex vivo culturing provides a unique and powerful opportunity to modify and enhance the DCs. As such, a variety of genetic engineering approaches have been employed to optimize DC vaccines, including the introduction of messenger RNA and small interfering RNA, viral gene transduction, and even fusion with whole tumor cells...
November 2016: Cytotherapy
Amy K Erbe, Wei Wang, Jacob Goldberg, Mikayla Gallenberger, KyungMann Kim, Lakeesha Carmichael, Dustin Hess, Eneida A Mendonca, Yiqiang Song, Jacquelyn A Hank, Su-Chun Cheng, Sabina Signoretti, Michael Atkins, Alexander Carlson, James W Mier, David J Panka, David F McDermott, Paul M Sondel
BACKGROUND: Fc-gamma receptors (FCGRs) are expressed on immune cells, bind to antibodies, and trigger antibody-induced cell-mediated anti-tumor responses when tumor-reactive antibodies are present. The affinity of the FCGR/antibody interaction is variable and dependent upon FCGR polymorphisms. Prior studies of cancer patients treated with immunotherapy indicate that FCGR polymorphisms can influence antitumor response for certain immunotherapies that act via therapeutically administered mAbs or via endogenous tumor-reactive antibodies induced from tumor antigen vaccines...
October 14, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Matthew R Collinson-Pautz, Kevin M Slawin, Jonathan M Levitt, David M Spencer
Therapeutic DNA-based vaccines aim to prime an adaptive host immune response against tumor-associated antigens, eliminating cancer cells primarily through CD8+ cytotoxic T cell-mediated destruction. To be optimally effective, immunological adjuvants are required for the activation of tumor-specific CD8+ T cells responses by DNA vaccination. Here, we describe enhanced anti-tumor efficacy of an in vivo electroporation-delivered DNA vaccine by inclusion of a genetically encoded chimeric MyD88/CD40 (MC) adjuvant, which integrates both innate and adaptive immune signaling pathways...
2016: PloS One
Zhuoran Zhang, Enzhuo Yang, Chunmiao Hu, Han Cheng, Crystal Y Chen, Dan Huang, Richard Wang, Yue Zhao, Lijun Rong, Marco Vignuzzi, Hongbo Shen, Ling Shen, Zheng W Chen
While we are approaching the global eradication of circulating wild-type polioviruses(PV), vaccination with oral poliovirus vaccine (OPV) has led to emergence of circulating vaccine-derived poliovirus (cVDPV) and vaccine-associated paralytic poliomyelitis (VAPP). Complete cessation of all poliovirus infections may require stopping use of OPV and formulating improved vaccines and new antiviral drugs. Currently, no licensed drugs are available to treat chronically infected poliovirus excretors. Here, we created a modified PV expressing Gaussia Luciferase (PV-GLuc) and developed a cell-based high-throughput screening (HTS) antiviral assay...
October 12, 2016: ACS Infectious Diseases
Yi Yang, Jing Lu, Hangfan Liu, Guoguo Jin, Ruihua Bai, Xiang Li, Dongyu Wang, Jimin Zhao, Youtian Huang, Kangdong Liu, Ying Xing, Ziming Dong
Dendritic cells (DC) have been exploited for vaccination against cancer for years. DC loading autologous tumor lysate (ATL-DC) have been assessed in ongoing clinical trials, but frequently do not meet expectation. In this study, we found that mice immunized with ATL-DC induced less protective anti-tumor effect than immunized with DC alone. The percentage of CD8(+) T cells and the lysis efficiency of CTLs to auto tumor cells in ATL-DC vaccination group was less than that of DC group. Moreover, vaccination of mice with ATL-DC also promoted tumor angiogenesis by analyzing the CD31 positive microvessel density and hemoglobin content of tumor specimens...
October 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Bo-Ram Lee, Ho Kyung Ko, Ju Hee Ryu, Keum Young Ahn, Young-Ho Lee, Se Jin Oh, Jin Hee Na, Tae Woo Kim, Youngro Byun, Ick Chan Kwon, Kwangmeyung Kim, Jeewon Lee
Efficient delivery of tumor-specific antigens (TSAs) to lymph nodes (LNs) is essential to eliciting robust immune response for cancer immunotherapy but still remains unsolved. Herein, we evaluated the direct LN-targeting performance of four different protein nanoparticles with different size, shape, and origin [Escherichia coli DNA binding protein (DPS), Thermoplasma acidophilum proteasome (PTS), hepatitis B virus capsid (HBVC), and human ferritin heavy chain (hFTN)] in live mice, using an optical fluorescence imaging system...
October 11, 2016: Scientific Reports
Jae Hee Cheon
Remarkable advances have been made in the treatment of inflammatory bowel disease (IBD) since the introduction of anti-tumor necrosis factor (TNF)-α agents, especially for patients who are refractory to or cannot tolerate conventional therapies. Currently, infliximab, adalimumab, and golimumab are available in the East Asian medical market, and these agents have been shown to be effective for inducing and maintaining long-term remission of IBD. Despite their clinical benefits, anti-TNF therapy can also lead to increased vulnerability to infections, development of autoimmune diseases and malignancy, and decreased immunogenicity of vaccinations...
October 10, 2016: Journal of Gastroenterology and Hepatology
Marla C McPherson, Hans H Cheng, Mary E Delany
Marek's disease (MD) is a lymphotropic and oncogenic disease of chickens that can lead to death in susceptible and unvaccinated host birds. The causative pathogen, MD virus (MDV), a highly oncogenic alphaherpesvirus, integrates into host genome near the telomeres. MD occurrence is controlled across the globe by biosecurity, selective breeding for enhanced MD genetic resistance, and widespread vaccination of flocks using attenuated serotype 1 MDV or other serotypes. Despite over 40 years of usage, the specific mechanism(s) of MD vaccine-related immunity and anti-tumor effects are not known...
October 5, 2016: Vaccine
Kayoko Waki, Akira Yamada
High Mobility Group Box 1 (HMGB1) is a member of the damage-associated molecular patterns (DAMPs), which cause inflammation and trigger innate immunity through Toll-like receptors (TLRs) 2/4 and the receptor for advanced glycation end products (RAGE). We examined the effect of glycyrrhizin, a selective inhibitor of HMGB1, on the induction of cytotoxic T-lymphocytes (CTLs) in mice. B6 mice, either OT-1 spleen cell-transferred or untransferred, were immunized with an s.c. injection of OVA257-264 peptide with topical imiquimod, and glycyrrhizin was mixed with the antigen peptide...
September 22, 2016: Cancer Science
Xiao-Ping Wang, Qiao-Xia Wang, Huan-Ping Lin, Bing Xu, Qian Zhao, Kun Chen
Alpha-fetoprotein (AFP) is a marker of hepatocellular carcinoma (HCC) and serves as a target for immunotherapy. However, current treatments targeting AFP are not reproducible and do not provide complete protection against cancer. This issue may be solved by developing novel therapeutic vaccines with enhanced immunogenicity that could effectively target AFP-expressing tumors. In this study, we report construction of a therapeutic peptide vaccine by linking heat shock protein 70 (HSP70) functional peptide to the AFP epitope to obtain HSP70-P/AFP-P...
October 4, 2016: Oncotarget
Woo Jung Shin, Hyun Jong Noh, Young-Woock Noh, Sohyun Kim, Soong Ho Um, Yong Taik Lim
A novel powder-form combination adjuvant system containing two immunostimulatory compounds was firstly developed and evaluated as a therapeutic intervention for cancer immunotherapy. With the help of hyaluronic acid (HA), water insoluble monophosphoryl lipid A (MPL), QS21 and imiquimod (R837), could be easily dispersed in aqueous solution and lyophilized as powder-form, which have an advantage in room-temperature storage stability compared with those conventional liquid formulation that requires cold storage...
January 2, 2017: Carbohydrate Polymers
Soheila Moeini, Mohsen Saeidi, Fatemeh Fotouhi, Mahdieh Mondanizdeh, Sadegh Shirian, Alireza Mohebi, Ali Gorji, Amir Ghaemi
The use of DNA vaccines has become an attractive approach for generating antigen-specific cytotoxic CD8(+) T lymphocytes (CTLs), which can mediate protective antitumor immunity. The potency of DNA vaccines encoding weakly immunogenic tumor-associated antigens (TAAs) can be improved by using an adjuvant injected together with checkpoint antibodies. In the current study, we evaluated whether the therapeutic effects of a DNA vaccine encoding human papilloma virus type 16 (HPV-16) E7 can be enhanced by combined application of an immune checkpoint blockade directed against the programmed death-1 (PD-1) pathway and secondary lymphoid tissue chemokine (SLC) also known as CCL21 adjuvant, in a mouse cervical cancer model...
October 3, 2016: Archives of Virology
Kirsteen M Tullett, Ingrid M Leal Rojas, Yoshihito Minoda, Peck S Tan, Jian-Guo Zhang, Corey Smith, Rajiv Khanna, Ken Shortman, Irina Caminschi, Mireille H Lahoud, Kristen J Radford
DC-based vaccines that initiate T cell responses are well tolerated and have demonstrated efficacy for tumor immunotherapy, with the potential to be combined with other therapies. Targeting vaccine antigens (Ag) directly to the DCs in vivo is more effective than cell-based therapies in mouse models and is therefore a promising strategy to translate to humans. The human CD141(+) DCs are considered the most clinically relevant for initiating CD8(+) T cell responses critical for killing tumors or infected cells, and they specifically express the C-type lectin-like receptor CLEC9A that facilitates presentation of Ag by these DCs...
May 19, 2016: JCI Insight
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