Article
Materials Science, Biomaterials
Dayananda Kasala, Soo-Hwan Lee, JinWoo Hong, Eonju Oh, A-Rum Yoon, Chae-Ok Yun
Summary: The study demonstrates that a nanohybrid complex incorporating decorin and interleukin-12 with oncolytic adenovirus can enhance antitumor efficacy while reducing antiviral immune response, making it more favorable for oncolytic virotherapy.
BIOMATERIALS SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Xiuliang Cui, Lu Han, Longjiu Cui, Gongbo Fu, Erdong Liu, Duowei Wang, Bin Song, Yongxiang Zhang, Wenxia Zhou, Hongyang Wang, Jing Fu
Summary: The heterogeneity of tumor immune microenvironment plays important roles in the development and immunotherapy response of hepatocellular carcinoma. Machine learning algorithms were used to introduce immune index (IMI) and gene model (IMIG), which can predict the prognosis, classification, and immune checkpoint blockade treatment response of HCC.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Katja Ursic, Spela Kos, Urska Kamensek, Maja Cemazar, Simona Miceska, Bostjan Markelc, Simon Bucek, Barbara Staresinic, Veronika Kloboves Prevodnik, Richard Heller, Gregor Sersa
Summary: The study found that IL-12 enhanced the antitumor effect of ECT in poorly immunogenic B16F10 melanoma, while it did not significantly improve the therapeutic outcome of ECT in more immunogenic 4T1 mammary carcinoma and CT26 colorectal carcinoma. The effectiveness of the combination therapy depends on tumor immune status, with ECT being more effective in more immunogenic tumors and gene electrotransfer showing greater contribution in less immunogenic tumors.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Chemistry, Multidisciplinary
Nasha Qiu, Guowei Wang, Jinqiang Wang, Quan Zhou, Mengyu Guo, Yaling Wang, Xuhao Hu, Huige Zhou, Ru Bai, Min You, Zhen Zhang, Chunying Chen, Ying Liu, Youqing Shen
Summary: A novel IL12 gene-delivery vector was designed to efficiently transfect both cancer cells and TAMs, turning them into a factory for IL12 production, which effectively activates anticancer immune responses and remodels the tumor microenvironment. The intravenously administered vector slows tumor growth and doubles survival in three animal models with minimal systemic toxicities.
ADVANCED MATERIALS
(2021)
Article
Engineering, Biomedical
Zeyu Xiao, Duo Wang, Chan Wang, Zerong Chen, Cuiqing Huang, Yuan Yang, Lin Xie, Lulu Zhang, Lingling Xu, Ming-Rong Zhang, Kuan Hu, Zhou Li, Liangping Luo
Summary: Intratumoral immunotherapeutic hydrogel administration is effective in inducing a durable antitumor immune response. A ternary hydrogel composed of PVA, PEI, and magnesium ions has been developed to reverse the immunologically cold phenotype of breast tumors to a hot phenotype by upregulating PD-L1 expression and promoting M1-like macrophage polarization. PEI hydrogel encapsulating an ICB inhibitor exhibits synergistic effects in eliminating tumors and preventing relapse after surgical resection.
MATERIALS TODAY BIO
(2022)
Article
Immunology
Shujia Chen, Peiyan Liu, Lili Zhao, Ping Han, Jie Liu, Hang Yang, Jia Li
Summary: This study provides insights into the tumor microenvironment status in patients with hepatocellular carcinoma (HCC) and lays the foundation for immunotherapy and the selection of sensitive drugs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biophysics
Jiakai Xing, Jiaxin Jia, Xiaofeng Cong, Ziling Liu, Quanshun Li
Summary: The novel carrier PEN successfully transfected miR-29a into cancer cells, inhibiting cell proliferation and inducing cell cycle arrest, showcasing a potential anti-cancer effect.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2021)
Article
Oncology
Eileen E. Parkes, Kienan I. Savage, Tong Lioe, Clinton Boyd, Sophia Halliday, Steven M. Walker, Keith Lowry, Laura Knight, Niamh E. Buckley, Andrena Grogan, Gemma E. Logan, Alison Clayton, Jane Hurwitz, Stephen J. Kirk, Jiamei Xu, Fatima Abdullahi Sidi, Matthew P. Humphries, Victoria Bingham, Jaqueline A. James, Colin R. James, D. Paul Harkin, Richard D. Kennedy, Stuart A. McIntosh
Summary: This study evaluates the predictive value of the DNA-damage immune-response (DDIR) signature for neoadjuvant chemotherapy response in early breast cancer. The results suggest that DDIR positivity is associated with immune infiltration and upregulated immune-checkpoint gene expression, and may identify a subgroup sensitive to anthracycline chemotherapy. The transcriptomic data indicate that induction with anthracycline-containing regimens in immune restricted, cold tumors may be effective for immune priming.
BRITISH JOURNAL OF CANCER
(2022)
Article
Medicine, Research & Experimental
Youji Hong, Yvette Robbins, Xinping Yang, Wojciech K. Mydlarz, Anastasia Sowers, James B. Mitchell, James L. Gulley, Jeffrey Schlom, Sofia R. Gameiro, Cem Sievers, Clint T. Allen
Summary: This study demonstrates that local administration of a tumor-targeted IL-12 antibody fusion protein can achieve potent immune control of established tumors with low doses to avoid systemic toxicity. The treatment leads to reinvigoration and proliferation of exhausted T lymphocytes, induction of Th1 immunity, and a decrease in regulatory T cells and suppressive myeloid cells. Single-cell analysis also reveals similar IL-12 receptor expression patterns in human head and neck carcinomas.
Article
Engineering, Biomedical
Yu Xia, Guoyi Tang, Yi Chen, Changbing Wang, Min Guo, Tiantian Xu, Mingqi Zhao, Yongjian Zhou
Summary: RNA interference (RNAi) is a promising method for treating malignant tumors, and in this study, RGDfC-SeNPs were successfully synthesized as a tumor-targeted carrier for delivering siSox2 to HepG2 liver cancer cells. The results showed that RGDfC-Se@siSox2 effectively silenced Sox2, inhibited tumor cell proliferation, migration, and invasion, induced apoptosis through reactive oxygen species production and mitochondrial membrane potential disruption, and significantly inhibited tumor growth in mice bearing HepG2 tumors. These findings suggest that RGDfC-SeNPs could be a valuable gene carrier for specific gene-targeted therapy in HCC.
BIOACTIVE MATERIALS
(2021)
Article
Oncology
E. Antonio Chiocca, Arnold B. Gelb, Clark C. Chen, Ganesh Rao, David A. Reardon, Patrick Y. Wen, Wenya Linda Bi, Pierpaolo Peruzzi, Christina Amidei, Dan Triggs, Leah Seften, Grace Park, James Grant, Kyla Truman, Jill Y. Buck, Nira Hadar, Nathan Demars, John Miao, Taylor Estupinan, John Loewy, Kamal Chadha, Joseph Tringali, Laurence Cooper, Rimas Lukas
Summary: The combination of VDX-regulatable IL-12 gene therapy and nivolumab in recurrent glioblastoma patients has shown promising safety and potential therapeutic effects.
Review
Oncology
Jeaneen Venkatas, Moganavelli Singh
Summary: This article discusses the application and potential of interleukin-12 (IL-12) as an antitumor immunotherapeutic agent, emphasizing the need for localized gene therapy and the development of nano-delivery strategies for IL-12 in cancer treatment. The findings suggest that IL-12 has promising prospects in cancer immunotherapy, but its systemic delivery has limitations due to severe side effects. The use of nanomedicine provides new avenues to enhance therapeutic indices with minimal side effects, and combination therapy with other anticancer molecules can further potentiate the activity of IL-12. The results will aid researchers in developing immunotherapeutic nanovectors that synergistically enhance the therapeutic effect of the IL-12 gene to eliminate cancer cells.
CURRENT CANCER DRUG TARGETS
(2022)
Article
Immunology
Nerissa T. Viola, James E. Glassbrook, Jhansi R. Kalluri, Justin B. Hackett, Madison N. Wicker, Joshua Sternberg, Heather M. Gibson
Summary: This study reports the development and evaluation of an antibody-based IL-12-specific PET tracer. The tracer showed the ability to accurately monitor IL-12 production and uptake in an animal model, providing a noninvasive method to study immune processes such as tumor immunity, inflammation, and infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Ales Groselj, Masa Bosnjak, Tanja Jesenko, Maja Cemazar, Bostjan Markelc, Primoz Strojan, Gregor Sersa
Summary: This study presents the first-in-human clinical trial protocol for phIL12 GET as an adjuvant treatment to local ablative therapies. The trial aims to evaluate the safety and tolerability of phIL12 GET in patients with operable basal cell carcinomas in the head and neck region.
RADIOLOGY AND ONCOLOGY
(2022)
Article
Medicine, General & Internal
Selena Rashid, Amalia Ardeljan, Lexi R. Frankel, Matthew Cardeiro, Enoch Kim, Brittany M. Nagel, Kazuaki Takabe, Omar Rashid
Summary: This study aimed to evaluate the correlation between cytomegalovirus (CMV) infection and the incidence of bronchogenic carcinoma. Using a national database, patients with and without CMV infection histories were compared, and it was found that the incidence of bronchogenic carcinoma in the CMV group was 1.69% as compared to 6.08% in the control group. This study highlights the need for further investigation into how latent CMV infection alters the tumor microenvironment and the host immune system.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Review
Gastroenterology & Hepatology
Nerea Zabaleta, Carmen Unzu, Nicholas D. Weber, Gloria Gonzalez-Aseguinolaza
Summary: In this review, the authors discuss gene therapy involving the use of recombinant adeno-associated virus vectors for the treatment of inherited liver diseases, including ongoing clinical trials that are producing promising results. Clinical testing has revealed several key challenges associated with gene therapy, such as the interaction of the immune system with the vector and the risk of adverse events. The permanent modification of the host genome through gene editing raises concerns about oncogenicity and requires careful evaluation.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Oncology
Assunta Cirella, Elixabet Bolanos, Claudia Augusta Di Trani, Carlos E. de Andrea, Sandra Sanchez-Gregorio, Inaki Etxeberria, Jose Gonzalez-Gomariz, Irene Olivera, Davide Brocco, Javier Glez-Vaz, Carlos Luri-Rey, Arantza Azpilikueta, Inmaculada Rodriguez, Myriam Fernandez-Sendin, Josune Egea, Inaki Eguren, Miguel F. Sanmamed, Belen Palencia, Alvaro Teijeira, Pedro Berraondo, Ignacio Melero
Summary: IL12 and IL18 combination therapy can enhance antitumor effects. Intratumoral administration of DR-18 construct can avoid systemic toxicity and improve therapeutic efficiency.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Oncology
Claudia Augusta Di Trani, Assunta Cirella, Leire Arrizabalaga, Angela Bella, Myriam Fernandez-Sendin, Joan Salvador Russo-Cabrera, Celia Gomar, Irene Olivera, Elizabeth Bolanos, Jose Gonzalez-Gomariz, Maite Alvarez, Inaki Etxeberria, Belen Palencia, Alvaro Teijeira, Ignacio Melero, Pedro Berraondo, Fernando Aranda
Summary: Previous studies have found that local delivery of tumor antigen-specific CD8(+) T lymphocytes transiently expressing single-chain IL-12 mRNA is highly effective in treating tumors. In this study, intracavitary adoptive T cell therapy was used to treat peritoneal dissemination of B16-OVA and PANC02-OVA tumors, and it was found that intraperitoneal administration of T cells promoted homing to the omentum more effectively than intravenous administration. Transient IL-12 expression resulted in a favorable reprogramming of the tumor immune microenvironment and longer persistence of transferred T lymphocytes, leading to the development of immunity to endogenous antigens after primary tumor eradication.
Review
Biology
Daniel Jerico, Karol M. Cordoba, Ana Sampedro, Lei Jiang, Gilles Joucla, Charlotte Cabanne, Jose Luis Lanciego, Paolo G. Martini, Pedro Berraondo, Matias A. Avila, Antonio Fontanellas
Summary: Rare diseases, especially monogenic diseases, have attracted pharmaceutical companies' interest in drug research. Acute intermittent porphyria is one of these rare diseases, and there are already some treatment methods, but there are still many unanswered questions.
Article
Toxicology
Maritza Roxana Garcia Garcia, Noelia Casares, Luz Andrea Martinez Perez, Efren Juarez Curiel, Andres Alberto de Jesus Hernandez, Nina Bogdanchikova, Diana Garibo, Ana G. Rodriguez-Hernandez, Alexey Pestryakov, Sandra Castro Gamboa, Luis Felipe Arias Ruiz, Olivia Torres Bugarin, Pedro Berraondo
Summary: This study evaluated the ability of silver nanoparticles (AgNP) to induce immunogenic cell death (ICD) and their anti-cancer effects in vitro and in vivo. The results showed that AgNP had anti-proliferative effects on CT26 and MCA205 cell lines and could release calreticulin. However, immunization with AgNP-treated tumor cell debris failed to induce a protective immune response in vivo. Further research is needed to explore the combination of AgNP with other ICD inducers to enhance their anti-tumor effect in vivo.
JOURNAL OF IMMUNOTOXICOLOGY
(2023)
Article
Oncology
Maite Alvarez, Carmen Molina, Saray Garasa, Maria C. Ochoa, Maria E. Rodriguez-Ruiz, Gabriel Gomis, Assunta Cirella, Irene Olivera, Javier Glez-Vaz, Jose Gonzalez-Gomariz, Carlos luri-Rey, Arantza Azpilikueta, Elixabet Bolanos, Alvaro Teijeira, Pedro Berraondo, Marisol Quintero, Ignacio Melero
Summary: The poly I:C-based viral mimetic BO-112 has been found to effectively reduce tumor metastasis when intratumorally delivered, particularly when combined with systemic anti-PD-1 mAbs. This neoadjuvant immunotherapy approach relies on antigen-specific effector CD8 T cells and cDC1 antigen-presenting cells.
Article
Cell Biology
Irene Olivera, Elixabet Bolanos, Jose Gonzalez-Gomariz, Sandra Hervas-Stubbs, Karina V. Marino, Carlos Luri-Rey, Inaki Etxeberria, Assunta Cirella, Josune Egea, Javier Glez-Vaz, Saray Garasa, Maite Alvarez, Inaki Eguren-Santamaria, Sonia Guedan, Miguel F. Sanmamed, Pedro Berraondo, Gabriel A. Rabinovich, Alvaro Teijeira, Ignacio Melero
Summary: Engineering tumor-specific CD8 T cells with IL-12 mRNA enhances their therapeutic potency when delivered intratumorally.
CELL REPORTS MEDICINE
(2023)
Article
Cell Biology
Maria Carmen Ochoa, Sandra Sanchez-Gregorio, Carlos E. de Andrea, Saray Garasa, Maite Alvarez, Irene Olivera, Javier Glez-Vaz, Carlos Luri-Rey, Inaki Etxeberria, Assunta Cirella, Arantza Azpilikueta, Pedro Berraondo, Josepmaria Argemi, Bruno Sangro, Alvaro Teijeira, Ignacio Melero
Summary: Immune checkpoint-inhibitor combinations are the best therapeutic option for advanced hepatocellular carcinoma (HCC) patients, and the efficacy can be further improved by combining recombinant IL-2 or anti-CD137 mAb with anti-CTLA-4 + anti-PD1 mAbs treatment. A multifocal HCC model was developed to test immunotherapies, and the combination of tumor-specific adoptive T cell therapy with aCTLA-4/aPD1/rIL2 or aCTLA-4/aPD1/aCD137 regimens showed synergistic efficacy. The combined immunotherapy treatments enhanced T cell infiltration and the intratumoral performance of T lymphocytes.
CELL REPORTS MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Nicholas D. Weber, Leticia Odriozola, Irene Ros-Ganan, Guillermo Garcia-Porrero, David Salas, Josepmaria Argemi, Jean-Philippe Combal, Takashi K. Kishimoto, Gloria Gonzalez-Aseguinolaza
Summary: The study demonstrates that repeat administration of rAAV combined with immunotolerant nanoparticles can effectively treat PFIC3 in infant mice and reduce the risk of liver cancer.
Review
Biotechnology & Applied Microbiology
Helena Costa-Verdera, Carmen Unzu, Erika Valeri, Sahil Adriouch, Gloria Gonzalez Aseguinolaza, Federico Mingozzi, Anna Kajaste-Rudnitski
Summary: As the clinical experience in AAV vector-based gene therapies grows, there is a need to better understand and control the host immune responses. Our current understanding of the immune responses to AAV gene therapies is limited, which is further hindered by the lack of replication of clinical findings in preclinical animal models.
HUMAN GENE THERAPY
(2023)
Article
Oncology
Elham Khodayari Moez, Matthew T. Warkentin, Yonathan Brhane, Stephen Lam, John K. Field, Geoffrey Liu, Javier J. Zulueta, Karmele Valencia, Miguel Mesa-Guzman, Andrea Pasquier Nialet, Sukhinder Atkar-Khattra, Michael P. A. Davies, Benjamin Grant, Kiera Murison, Luis M. Montuenga, Christopher Amos, Hilary A. Robbins, Mattias Johansson, Rayjean J. Hung
Summary: The study found that circulating protein markers can help differentiate malignant from benign pulmonary nodules. Using blood samples from international low-dose computed tomography screening studies, 36 potential protein markers were identified. The protein burden scores for overall nodule malignancy and imminent tumors were summarized, with a focus on the significantly higher scores for malignant nodules in LungRADS category 4. However, further validation is needed before clinical implementation.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Cell Biology
Susana Aguilar, Paula Garcia-Olloqui, Lidia Amigo-Moran, Jose Luis Toran, Juan Antonio Lopez, Guillermo Albericio, Gloria Abizanda, Diego Herrero, Africa Vales, Saray Rodriguez-Diaz, Marina Higuera, Ruben Garcia-Martin, Jesus Vazquez, Carmen Mora, Gloria Gonzalez-Aseguinolaza, Felipe Prosper, Beatriz Pelacho, Antonio Bernad
Summary: Oxidative stress-induced myocardial apoptosis and necrosis play a critical role in ischemic infarction. This study identified and validated miR-935 as a highly differentially expressed miRNA in exosomes derived from human cardiac progenitor cells (CPC). Reduction of miR-935 expression promotes oxidative stress-associated apoptosis. Together with other exosomal miRNA members, miR-935 may counteract oxidative stress-related apoptosis in the CPC microenvironment.
Article
Pharmacology & Pharmacy
Andoni Gomez-Moreno, Enara San Sebastian, Jennifer Moya, Pilar Gomollon-Zueco, Sergio Isola, Africa Vales, Gloria Gonzalez-Aseguinolaza, Carmen Unzu, Urtzi Garaigorta
Summary: Gene therapy is a promising approach to treat inherited metabolic liver disorders. This study shows that using topoisomerase inhibitors can increase the expression of viral genes in non-dividing hepatic cells, with a greater effect seen in the integration-deficient LV strain. These effects are associated with increased DNA damage response.
Meeting Abstract
Oncology
Irene Olivera, Elixabet Bolanos, Jose Gonzalez-Gomariz, Sandra Hervas-Stubbs, Karina V. Marino, Carlos Luri-Rey, Inaki Etxeberria, Assunta Cirella, Josune Egea, Javier Glez-Vaz, Saray Garasa, Maite Alvarez, Inaki Eguren-Santamaria, Sonia Guedan, Miguel F. Sanmamed, Pedro Berraondo, Gabriel Rabinovich, Alvaro Teijeira, Ignacio Melero
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Irene Ros-Ganan, Mirja Hommel, Laia Trigueros-Motos, Blanche Tamarit, Estefania Rodriguez-Garcia, David Salas, Guiomar Perez, Anne Douar, Jean Philippe Combal, Bernard Benichou, Veronica Ferrer, Gloria Gonzalez-Aseguinolaza
Summary: This study tested the effectiveness of an enzyme called IdeS in cleaving neutralizing antibodies and improving the transduction efficiency of AAV-mediated gene therapy. The results showed that IdeS was able to efficiently cleave human IgG and had varying effects on different AAV serotypes in vivo. The study suggests that preconditioning with IdeS could provide a unique treatment opportunity for patients who are excluded from gene therapy due to elevated levels of anti-AAV antibodies.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2022)