Evaluation of clinical and radiographic outcome of premixed injectable MTA and conventional MTA as pulpotomy medicament in primary teeth : A split mouth randomised control trial - PIMTAP

Start Date22 Jul 2023

Sponsor / Collaborator-

NCT02556463 / TerminatedPhase 1

A Phase I, First-Time-in-Human Study of MEDI9197, a TLR 7/8 Agonist, Administered Intratumorally as a Single Agent in Subjects With Solid Tumors or CTCL and in Combination With Durvalumab and/or Palliative Radiation in Subjects With Solid Tumors

To evaluate MEDI9197 when administered by intratumoral injection to subjects with solid tumors and in combination with durvalumab in subjects with solid tumors.

Start Date04 Nov 2015

Sponsor / Collaborator

MedImmune LLC

100 Clinical Results associated with Telratolimod

100 Translational Medicine associated with Telratolimod

100 Patents (Medical) associated with Telratolimod

Literatures (Medical) associated with Telratolimod

31 Jul 2024·Science Translational Medicine

A comparative immunological assessment of multiple clinical-stage adjuvants for the R21 malaria vaccine in nonhuman primates

Article

Author: Zarnitsyna, Veronika I. ; Hill, Adrian V. S. ; Shirreff, Lisa M. ; Xiao, Peng ; Santagata, Jordan M. ; Ha, NaYoung ; Rogers, Kenneth ; Tomai, Mark ; Arunachalam, Prabhu S. ; Fox, Christopher B. ; Spreng, Rachel L. ; Hu, Mengyun ; Kazmin, Dmitri ; Dutta, Sheetij ; Seaton, Kelly E. ; Prieto, Katherine ; Pulendran, Bali ; Julien, Jean-Philippe ; Villinger, Francois ; Spencer, Alexandra J. ; Feng, Yupeng ; Chottin, Claire ; Xie, Xia ; Dennison, S. Moses ; Tomaras, Georgia D.

Authorization of the Matrix-M (MM)–adjuvanted R21 vaccine by three countries and its subsequent endorsement by the World Health Organization for malaria prevention in children are a milestone in the fight against malaria. Yet, our understanding of the innate and adaptive immune responses elicited by this vaccine remains limited. Here, we compared three clinically relevant adjuvants [3M-052 + aluminum hydroxide (Alum) (3M), a TLR7/8 agonist formulated in Alum; GLA-LSQ, a TLR4 agonist formulated in liposomes with QS-21; and MM, the now-approved adjuvant for R21] for their capacity to induce durable immune responses to R21 in macaques. R21 adjuvanted with 3M on a 0, 8, and 23–week schedule elicited anti-circumsporozoite antibody responses comparable in magnitude to the R21/MM vaccine administered using a 0-4-8–week regimen and persisted up to 72 weeks with a half-life of 337 days. A booster dose at 72 weeks induced a recall response similar to the R21/MM vaccination. In contrast, R21/GLA-LSQ immunization induced a lower, short-lived response at the dose used. Consistent with the durable serum antibody responses, MM and 3M induced long-lived plasma cells in the bone marrow and other tissues, including the spleen. Furthermore, whereas 3M stimulated potent and persistent antiviral transcriptional and cytokine signatures after primary and booster immunizations, MM induced enhanced expression of interferon- and T H 2-related signatures more highly after the booster vaccination. Collectively, these findings provide a resource on the immune responses of three clinically relevant adjuvants with R21 and highlight the promise of 3M as another adjuvant for malarial vaccines.

01 Nov 2023·Advanced healthcare materials

Broad and Durable Humoral Responses Following Single Hydrogel Immunization of SARS‐CoV‐2 Subunit Vaccine

Article

Author: King, Neil P ; Ou, Ben S ; Appel, Eric A ; Zhou, Xueting ; Baillet, Julie ; Saouaf, Olivia M ; Yan, Jerry ; Bruun, Theodora U J

Abstract:

Most vaccines require several immunizations to induce robust immunity, and indeed, most SARS‐CoV‐2 vaccines require an initial two‐shot regimen followed by several boosters to maintain efficacy. Such a complex series of immunizations unfortunately increases the cost and complexity of populations‐scale vaccination and reduces overall compliance and vaccination rate. In a rapidly evolving pandemic affected by the spread of immune‐escaping variants, there is an urgent need to develop vaccines capable of providing robust and durable immunity. In this work, a single immunization SARS‐CoV‐2 subunit vaccine is developed that can rapidly generate potent, broad, and durable humoral immunity. Injectable polymer–nanoparticle (PNP) hydrogels are leveraged as a depot technology for the sustained delivery of a nanoparticle antigen (RND‐NP) displaying multiple copies of the SARS‐CoV‐2 receptor‐binding domain (RBD) and potent adjuvants including CpG and 3M‐052. Compared to a clinically relevant prime‐boost regimen with soluble vaccines formulated with CpG/alum or 3M‐052/alum adjuvants, PNP hydrogel vaccines more rapidly generated higher, broader, and more durable antibody responses. Additionally, these single‐immunization hydrogel‐based vaccines elicit potent and consistent neutralizing responses. Overall, it is shown that PNP hydrogels elicit improved anti‐COVID immune responses with only a single administration, demonstrating their potential as critical technologies to enhance overall pandemic readiness.

01 Apr 2023·Biochemical and biophysical research communications

Anti-TNFR2 enhanced the antitumor activity of a new HMGN1/3M-052 stimulated dendritic cell vaccine in a mouse model of colon cancer

Article

Author: Nie, Yingjie ; Nie, Yujie ; Li, Linzhao ; Gui, Huan ; Zhu, Lan ; Pan, Runsang ; Chen, Xin ; Wang, Chenglv ; Yang, De ; Jing, Qianyu ; Zhang, Xiangyan ; Chen, Shuanghui ; Wang, Mengjiao

Immunotherapy is the new approach for cancer treatment that can be achieved through several strategies, one of which is dendritic cells (DCs) vaccine therapy. However, traditional DC vaccination lacks accurate targeting, so DC vaccine preparation needs to be optimized. Immunosuppressive CD4⁺Foxp3⁺ regulatory T cells (Tregs) in the tumor microenvironment can promote tumor immune escape. Therefore, targeting Tregs has become a strategy for tumor immunotherapy. In this study, we found that HMGN1 (N1, a dendritic cell-activating TLR4 agonist) and 3M-052 (a newly synthesized TLR7/8 agonist) synergistically stimulate DCs maturation and increase the production of proinflammatory cytokines TNFα and IL-12. In a colon cancer mice model, vaccination with N1 and 3M-052 stimulated and tumor antigen-loaded DCs combined with anti-TNFR2 inhibited tumor growth in mice, and the antitumor effect was mainly achieved through stimulation of cytotoxic CD8 T cell activation and depletion of Tregs. Overall, the combinating of DC activation by N1 and 3M-052 with inhibition of Tregs by antagonizing TNFR2 as a therapeutic strategy may represent a more effective strategy for cancer treatment.

News (Medical) associated with Telratolimod

07 Mar 2024

·www.businesswire.com

The Access to Advanced Health Institute Receives up to $12.7 Million to Develop Novel NanoAlum Adjuvant Formulation for Better Protection Against Tuberculosis and Pandemic Influenza

SEATTLE--( BUSINESS WIRE )--The Access to Advanced Health Institute (AAHI) announced today that it has been awarded the first stage of funding for a $12.7-million project through the Medical CBRN Defense Consortium (MCDC) Other Transaction Authority (OTA) to develop a novel immune-stimulating adjuvant formulation that will improve the human immune response to vaccines, providing broader and longer lasting protection against disease. This five-year prototype project will support AAHI’s development and optimization of “NanoAlum” – a novel nanoparticle adjuvant formulation, made from aluminum salts (“alum”). Alum has been used for nearly 100 years to enhance immune responses to vaccines, and vaccines adjuvanted with alum work well against some diseases, such as hepatitis A and B and pneumococcus. Alum-adjuvanted vaccines have been less effective against diseases such as tuberculosis and influenza, which are more complex to target and can be challenging to manufacture because they require special sterilization methods. AAHI’s NanoAlum formulation changes the size, shape, and charge of alum particles to enhance specific immune responses for better vaccine protection against complex diseases. Vaccines formulated with NanoAlum can be sterilized using standard methods for ease of manufacture, and NanoAlum is designed to be stable at extreme temperatures to ensure accessibility in low-resource areas of the world, such as those most burdened by tuberculosis. “The team hopes to get a better understanding of how the physical characteristics of adjuvant formulations alter and improve the human immune response to vaccines,” says Christopher Fox, PhD, Senior Vice President of Formulations at AAHI, and the lead scientist on the project. “By optimizing those characteristics in a new adjuvant formulation, we may unlock approaches to providing improved protection against the most complex and difficult diseases to target, like tuberculosis and influenza.” The MCDC prototype project will evaluate AAHI’s NanoAlum formulated with 3M’s immune-stimulating “3M-052” molecule – an extremely promising adjuvant characterized as a toll-like receptor (TLR) agonist. Formulations of 3M-052 have demonstrated ability to generate robust and durable immune responses and are currently being used in clinical trials of several HIV vaccines with encouraging results. Adjuvant formulations containing TLR agonists are a critical component of some of today’s newest and most successful vaccines, including currently licensed vaccines against shingles (Shingrix®), respiratory syncytial virus (AREXVY®), malaria (RTS,S®), and COVID-19 (Covaxin®). AAHI’s prototype project for MCDC will pair the combined 3M-052 and NanoAlum formulation with tuberculosis and pandemic influenza vaccine antigens. The resulting vaccine candidates will be evaluated through preclinical studies and toxicology testing to prepare for use in clinical trials. “Currently available vaccine technology does not yet provide highly effective solutions that prevent infection and reduce or eliminate transmission against some of the most difficult and pervasive infectious diseases worldwide,” says Corey Casper, MD, MPH, CEO of AAHI. “Adjuvant formulations, particularly TLR agonists, have proven to be the most efficient technology to date, but they must be formulated to be safe and effective when used in human vaccines. This award will allow us to advance the oldest and safest vaccine adjuvant technology and combine it with the newest and most promising adjuvant molecule in a way that can safely enhance modern vaccines and do so in a way that is easily manufacturable and accessible to people around the globe. We hope this work will lead to accessible and potent vaccines that reduce the burden of tuberculosis and pandemic influenza, two of the leading infectious disease killers across the world.” AAHI’s NanoAlum research project is supported by federal funds from the Department of Defense under OTA number #W15QKN-16-9-1002. The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes, notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the U.S. Government. AAHI is a nonprofit biotech research institute located in Seattle, Washington, that combines the high-quality science of an academic research organization with the product development capabilities of a biotech company to help combat some of the world’s deadliest diseases, including infectious diseases such as COVID-19, mosquito and tick-borne diseases, cancer, fungal and parasitic infections, and other non-communicable diseases. For nearly three decades, AAHI, previously known as the Infectious Disease Research Institute, has focused on creating immune-enhancing technologies that improve the body’s natural response to disease. Through collaborations, AAHI brings innovative products from the lab to the clinic to the people, furthering AAHI’s mission to bring together the best experts, technologies, and platforms to create accessible, high-quality products and solutions. AAHI is working to build a world in which every person has access to tools that harness their immune system and allow them to live a healthy life free of illness and disease. For more information, go to AAHI.org or follow us on LinkedIn .

Vaccine

15 Feb 2023

·www.businesswire.com

The Access to Advanced Health Institute Announces $3M Award to Develop an Intranasal Pan-Viral Countermeasure against Respiratory Viruses

SEATTLE--( BUSINESS WIRE )--The Access to Advanced Health Institute (AAHI) announced today that it has been awarded up to $3M through the Defense Innovation Unit (DIU) Other Transaction Authority (OTA) to pursue a prototype project as part of the U.S. Department of Defense (DoD) Project Panacea and the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense’s (JPEO-CBRND) Joint Project Manager for Chemical, Biological, Radiological, and Nuclear Medical (JPM CBRN Medical) Vaccine Acceleration by Modular Progression (VAMP) program. AAHI will be working with the DIU and JPM CBRN Medical to develop a prototype nasal spray using AAHI’s novel formulation of two adjuvants, substances that enhance immune responses. AAHI’s adjuvant formulation platform enables development of temperature-stable products that can be easily distributed and stored to support the health and safety of warfighters. Because of unique military conditions, global presence, and need to operate in contested environments, military personnel need medical treatments with multiple benefits and are useful against a broad range of challenges such as newly emerging, highly transmissible, and/or rapidly mutating respiratory viruses. Effective medical countermeasures should be protective against a broad variety of viral threats, self-administrable for efficient uptake, and temperature stable to survive stringent military logistics. AAHI will use its adjuvant formulation platform to develop a prototype product that promises to shorten timelines for emergency response to and mitigate impacts from biological threats. AAHI’s collaboration with the DoD will build on AAHI’s over two decades of formulation expertise and broad portfolio of adjuvant formulations. This prototype product will rely on AAHI’s formulations of two different adjuvants, SLA and 3M-052, each of which stimulates a Toll-like receptor (TLR) immune pathway, to stimulate trained immunity and provide non-specific protection against the threat of respiratory infection. AAHI’s formulations of novel synthetic TLR4 agonists (known as “GLA” and “SLA”) have been shown in preclinical vaccinations to protect against influenza and other infectious diseases. AAHI’s formulations of 3M’s novel 3M-052 compound, a TLR7/8 agonist, likewise have demonstrated efficacy against influenza and COVID-19, as well as other infectious diseases. AAHI scientists will leverage their development and optimization of a similar intranasal multiple-agonist formulation that in preclinical vaccinations has induced simultaneous mucosal and systemic immune responses against influenza, COVID-19, and amebiasis (supported by the National Institute of Health National Institute of Allergy and Infectious Diseases (#HHSN272201800025C)). “This winter we have seen our hospitals and clinics overwhelmed with patients suffering from a broad range of respiratory viruses,” said Dr. Corey Casper, Chief Executive Officer at AAHI and Principal Investigator for the award. “A nasal spray that is easy to self-administer, temperature stable, and broadly protective against multiple respiratory viruses could greatly reduce the burden of pandemic and endemic viruses around the globe.” The 18-month project is focused on development of a prototype small-molecule nasal spray as prophylaxis for a variety of respiratory diseases, including novel viruses and newly emerging variants of existing viruses AAHI scientists will test the nasal spray against pandemic influenza and Nipah virus in preclinical studies; if successful, the activities of the award will allow for the rapid initiation of Phase 1 clinical trials in humans. A temperature-stable and broadly protective nasal spray could be rapidly deployed better to protect warfighters, and ultimately civilians, against dangerous viral pathogens. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the U.S. Government. AAHI is a nonprofit biotech research institute located in Seattle, Washington, that combines the high-quality science of an academic research organization with the product-development capabilities of a biotech company to help combat some of the world’s deadliest diseases, including COVID-19, cancer, fungal and parasitic infections, and other non-communicable diseases. For nearly three decades, AAHI, previously known as the Infectious Disease Research Institute, has focused on creating immune-enhancing technologies that improve the body’s natural response to disease. Through collaborations, AAHI brings innovation from the lab to the clinic to the people, furthering AAHI’s mission to bring together the best experts, technologies, and platforms to create accessible, high-quality products and solutions. AAHI is working to build a world in which every person has access to tools that harness their immune system and allow them to live a healthy life free of illness and disease. For more information, go to AAHI.org or follow us on LinkedIn .

Vaccine

01 Dec 2022

·www.sciencedaily.com

Experimental COVID-19 vaccine offers long-term protection against severe disease

A newly published follow-up study has found that the Moderna mRNA vaccine and a protein-based vaccine candidate containing an adjuvant, a substance that enhances immune responses, still provide protection against lung disease in rhesus macaques one year after they had been vaccinated as infants. In 2021, a group of scientists led by researchers at the University of North Carolina at Chapel Hill, Weill Cornell Medicine and NewYork-Presbyterian reported that the Moderna mRNA vaccine and a protein-based vaccine candidate containing an adjuvant, a substance that enhances immune responses, elicited durable neutralizing antibody responses to SARS-CoV-2 during infancy in pre-clinical research. Now a follow-up study by the same group, published in Science Translational Medicine, has found that the 2-dose vaccines still provide protection against lung disease in rhesus macaques one year after they had been vaccinated as infants. The co-senior authors of the paper are Kristina De Paris, PhD, professor of microbiology and immunology at the UNC School of Medicine, Sallie Permar, MD, PhD, chair of the Department of Pediatrics at Weill Cornell Medicine, and Koen K.A. Van Rompay, DVM, PhD, leader of the Infectious Disease Unit at the California National Primate Research at the University of California, Davis. Co-first authors are Emma C. Milligan at the Children's Research Institute in the UNC School of Medicine and Katherine Olstad at the California National Primate Research Center. To evaluate SARS-CoV-2 infant vaccination, the researchers immunized two groups of eight infant rhesus macaques at the California National Primate Research Center at 2 months of age and again four weeks later. Each animal received one of two vaccine types: a preclinical version of the Moderna mRNA vaccine or a vaccine combining a protein developed by the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health with a potent adjuvant formulation. Consisting of 3M's molecular adjuvant 3M-052 formulated in a squalene emulsion by the Access to Advanced Health Institute (AAHI), the adjuvant formulation stimulates immune responses by engaging receptors on immune cells. "Following up on our SARS-CoV-2 infant rhesus macaque study, we gave the animals a high-dose challenge with a SARS-CoV-2 variant one year later to assess durability of vaccine-induced immune responses and their efficacy," Dr. De Paris said. "We found that both vaccines protected against lung disease, despite the fact that the challenge SARS-CoV-2 variants acquired numerous mutations in their spike protein that differed from the vaccine immunogen." Overall, the adjuvanted protein vaccine candidate maintained higher levels of neutralizing antibodies and provided superior protection compared to the mRNA vaccine, Dr. De Paris said. These data imply that these vaccines are safe and highly effective when given to young infant macaques. Furthermore, the results inform the optimization and development of SARS-CoV-2 vaccines in a way that may reduce the need for frequent boosters and protect special populations that don't have fully developed immune systems, such as young children. "With COVID-19, young infants are one of the most vulnerable pediatric populations. This fall, we are seeing a sharp rise in hospitalizations due to respiratory virus disease in infants as the result of a confluence of SARS-CoV-2, flu, and RSV circulation," said Dr. Permar, who is also the Nancy C. Paduano Professor in Pediatrics at Weill Cornell Medicine and pediatrician-in-chief at NewYork-Presbyterian Komansky Children's Hospital. "We should take every opportunity to provide safe and effective vaccine immunity to our youngest patients, including considering COVID-19 vaccination earlier than the currently recommended 6 months of age." "This study emphasizes the need to get human infants immunized against SARS-CoV-2 as much as possible, as the benefits are clear and long-lasting. It also highlights the value of animal models in infectious disease research," Dr. Van Rompay said. "The lessons we learned and the resources and tools that were developed in the current study will be very valuable for future pandemic preparedness, to more effectively combat outbreaks with novel coronaviruses or other respiratory viruses in pediatric populations." This research was funded through grants from the National Institutes of Health (P01AI117915-06S1), (U54 CA260543), (P510D11107), (UM1 AI068618-15: HVTN/HPTN, CoVPN), (P30AI050410: UNC Center for AIDS Research), and (P30 CA016086: UNC-LCCC Flow Cytometry Core Facility). Other authors are Caitlin A. Williams, Michael Mallory, Patricia Cano, Kaitlyn A. Cross, Jennifer E. Munt, Carolina Garrido, Lisa Lindesmith, Jennifer Watanabe, Jodie L. Usachenko, Lincoln Hopkins, Ramya Immareddy, Yashavanth Shaan Lakshmanappa, Sonny R. Elizaldi, Jamin W. Roh, Rebecca L. Sammak, JoAnn L. Yee, Savannah Herbek, Trover Scobey, Dieter Miehlke, Genevieve Fouda, Guido Ferrari, Hongmei Gao, Xiaoying Shen, Pamela A. Kozlowski, David Montefiori, Michael Hudgens, Darin K. Edwards, Andrea Carfi, Kizzmekia S. Corbett, Barney S. Graham, Christopher B. Fox, Mark Tomai, Smita S. Iyer, Ralph Baric, Rachel Reader, and Dirk P. Dittmer.

VaccinemRNAImmunotherapyClinical Study

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Indication	Highest Phase	Country/Location	Organization	Date
Cutaneous T-Cell Lymphoma	Phase 1	US	MedImmune LLC	04 Nov 2015
Cutaneous T-Cell Lymphoma	Phase 1	CA	MedImmune LLC	04 Nov 2015
Cutaneous T-Cell Lymphoma	Phase 1	FR	MedImmune LLC	04 Nov 2015
Solid tumor	Phase 1	US	MedImmune LLC	04 Nov 2015
Solid tumor	Phase 1	CA	MedImmune LLC	04 Nov 2015
Solid tumor	Phase 1	FR	MedImmune LLC	04 Nov 2015
COVID-19	Preclinical	-	Access To Advanced Health Institute	15 Feb 2023
Influenza, Human	Preclinical	-	Access To Advanced Health Institute	15 Feb 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02556463 (Pubmed) Manual	Phase 1	Solid tumor	52	MEDI9197	kvliakpfod(jjppblocev) = gmshuvbpbk ytdvnlfezp (ndnjywxgxb ) View more	Positive	01 Oct 2020
				MEDI9197+durvalumab	smmayzgvwc(uxinoupmua) = rzmmuymnhm nerrqkcvlc (lvuxxlzwiy ) View more

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