Vaxart, Inc.’s Post

Traditional cancer vaccines have faced challenges, but recent advancements in identifying tumor markers and understanding the immune system have improved their efficacy. There are three main types of cancer vaccines: - 𝐕𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐟𝐨𝐫 𝐂𝐚𝐧𝐜𝐞𝐫 𝐏𝐫𝐞𝐯𝐞𝐧𝐭𝐢𝐨𝐧: Notable examples include the HPV vaccine for preventing cervical, vaginal, penile, anal, vulvar, and throat cancers, as well as the hepatitis B vaccine to prevent liver cancer. Developing prevention vaccines for cancers like breast cancer, which lacks a clear cause, is more challenging; - 𝐓𝐡𝐞𝐫𝐚𝐩𝐞𝐮𝐭𝐢𝐜 𝐕𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐭𝐨 𝐓𝐫𝐞𝐚𝐭 𝐂𝐚𝐧𝐜𝐞𝐫: These vaccines are for individuals with active cancer. Personalized vaccines, like Provenge for stage 4 prostate cancer, involve using a person's immune cells and a piece of their tumor to activate the immune system against cancer cells. Another example is T-VEC, an FDA-approved vaccine for metastatic melanoma, which uses a modified virus to stimulate the immune response; - 𝐕𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐭𝐨 𝐏𝐫𝐞𝐯𝐞𝐧𝐭 𝐂𝐚𝐧𝐜𝐞𝐫 𝐑𝐞𝐜𝐮𝐫𝐫𝐞𝐧𝐜𝐞: The BCG vaccine, FDA-approved for early-stage bladder cancer, activates the immune system by injecting inactivated tuberculosis bacteria into the bladder. A personalized vaccine for pancreatic cancer has shown promise in inciting a strong immune response, though it's still in early-phase clinical trials. Despite challenges, ongoing clinical trials offer hope for further advancements in cancer vaccines. See also my previous content about this topic: https://lnkd.in/dKAi56Um #marketintelligence #competitiveintelligence #marketsmind #pharmaceutical #vaccines

Dose escalation study of a personalized peptide-based neoantigen vaccine (EVX-01) in patients with metastatic melanoma 👉 Free access at https://lnkd.in/diPNsNgN (Journal for ImmunoTherapy of Cancer, May 28th 2024 by Sofie Kirial Mørk et al.) 🗝 Key Points: 1️⃣ Safety: No new vaccine-related serious adverse events were observed during dose escalation of EVX-01 2️⃣ Responses: 8 out of the 12 patients had objective clinical responses (6 partial response (PR) and 2 CR). 3️⃣ Immunology: EVX-01 induced peptide-specific CD4+ and/or CD8+T cell responses in all treated patients, with CD4+T cells as the dominating responses. 💡 Take-Home Message: Immunization with EVX-01-CAF09b in addition to anti-PD-1 therapy was well tolerated, elicited vaccine neoantigen-specific T cell responses, and was associated with encouraging objective responses. Further assessment of EVX-01 in combination with anti-PD-1 therapy is warranted. 📄 About the vaccine: Neoantigens (antigens derived from tumor mutations) can serve as targets for T cell-mediated antitumor immunity. Neoantigen-directed therapies are being investigated in multiple clinical trials. In this study, tumor-derived neoantigens were selected by the AI platform PIONEER and used in personalized therapeutic cancer peptide vaccines EVX-01. The vaccines were administered at 2-week intervals for a total of three intraperitoneal and three intramuscular injections. More about vaccines in melanoma at https://lnkd.in/dkNPHT5V 🙏 We thank the patients and families who participated in this study, and funding sources Innovation Fund Denmark and Kræftens Bekæmpelse (Danish Cancer Society). #melanoma #vaccines #neoantigens #immunotherapy #dkforsk Signe Koggersbøl Skadborg Benedetta Albieri Arianna Draghi Kalijn Bol Mo Kadivar Marie Christine Wulff Westergaard Joachim Granhøj Annie Borch Nadia Viborg Petersen Nikolas Thuesen Ida Svahn Rasmussen Lars Vibe Andreasen Rebecca Bach Dohn Christina Westmose Yde Nis Noergaard Torben Lorentzen Anders B. Sørensen Daniela Kleine-Kohlbrecher Anders Jespersen Dennis Christensen Jens Kringelum Marco Donia Sine Reker Hadrup Inge Marie Svane

An impressive finding of Neoantigen-specific CD4+ and CD8+ T cells both contribute to tumor control Neoantigen-specific T cell help outperforms non-specific help in multi-antigen DNA vaccination against cancer CD4+ T helper antigens are essential components of cancer vaccines, but the relevance of the source of these MHC class II-restricted antigens remains underexplored. To compare the effectiveness of tumor-specific versus tumor-unrelated helper antigens, we designed three DNA vaccines for the murine MC-38 colon carcinoma, encoding CD8+ T cell neoantigens alone (noHELP) or in combination with either “universal” helper antigens (uniHELP) or helper neoantigens (neoHELP). Both types of helped vaccines increased the frequency of vaccine-induced CD8+ T cells, and particularly uniHELP increased the fraction of KLRG1+ and PD-1low effector cells. However, when mice were subsequently injected with MC-38 cells, only neoHELP vaccination resulted in significantly better tumor control than noHELP. In contrast to uniHELP, neoHELP-induced tumor control was dependent on the presence of CD4+ T cells, while both vaccines relied on CD8+ T cells. In line with this, neoHELP variants containing wild-type counterparts of the CD4+ or CD8+ T cell neoantigens displayed reduced tumor control. These data indicate that optimal personalized cancer vaccines should include MHC class II-restricted neoantigens to elicit tumor-specific CD4+ T cell help. https://lnkd.in/e6jyYXf9

#mRNA_vaccines #CD8T_cellsb #LNP_Adjuvant | 𝗖𝗮𝗻 𝘄𝗲 𝗯𝗼𝗼𝘀𝘁 𝘁𝗵𝗲 𝗲𝗳𝗳𝗶𝗰𝗮𝗰𝘆 𝗼𝗳 𝗺𝗥𝗡𝗔 𝘃𝗮𝗰𝗰𝗶𝗻𝗲𝘀 𝗯𝘆 𝗲𝗻𝗵𝗮𝗻𝗰𝗶𝗻𝗴 𝗖𝗗𝟴+ 𝗧 𝗰𝗲𝗹𝗹 𝗿𝗲𝘀𝗽𝗼𝗻𝘀𝗲𝘀? 𝗔𝗶𝗺 This research explores how incorporating an IL-12 mRNA-LNP adjuvant can amplify the CD8+ T cell responses induced by mRNA vaccines, providing stronger immune protection. 𝗞𝗲𝘆 𝗙𝗶𝗻𝗱𝗶𝗻𝗴𝘀 mRNA-LNPs on their own did not trigger IL-12 production by myeloid cells. Vaccination with OVA mRNA-LNPs demonstrated CD8+ T cell response was independent of IL-12. Co-administration of IL-12 mRNA-LNPs with OVA mRNA-LNPs significantly boosted CD8+ T cell expansion and effector function. Enhanced CD8+ T cell memory was linked to better protection against Listeria monocytogenes-OVA and B16 F0-OVA melanoma. 𝗧𝗮𝗸𝗲 𝗛𝗼𝗺𝗲 𝗠𝗲𝘀𝘀𝗮𝗴𝗲 Adding an IL-12 mRNA-LNP adjuvant to mRNA vaccines is a promising strategy to enhance the protective immunity mediated by CD8+ T cells, potentially improving vaccine effectiveness against various pathogens and cancers. Check here for more: https://lnkd.in/gNXuWQ6h Special thanks to Emily Aunins, Tony Phan, Mohamad-Gabriel Alameh, Elisa Cruz-Morales, PhD, Cristian David, @Molly Bunkofske, @Garima Dwivedi, Ross Kedl, @Drew Weissman, and @Christopher Hunter for their groundbreaking work. Published in bioRxiv on July 31, 2024.

Access Vaccines Merck Discount Program Provides Lowest National Price on Gardasil The Access Vaccines Merck Discount Program provides members with the lowest national price on Gardasil. GARDASIL 9 is a vaccine for patients 9 through 45 years of age for the prevention of certain cancers and other diseases caused by 9 types of human papillomavirus (HPV). According to a CDC model in 2012-2016: In men, oropharyngeal cancer has been the most prevalent HPV-attributable cancer in the US. Certain HPV-related oropharyngeal cancers affect men (~10,500) ~5x more than women (~2,100). The oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Access Vaccines is proud to offer our members the lowest national price on Gardasil. Become a member today and save.

SARS-CoV-2’s ability to evolve quickly creates ongoing challenges for vaccine development. The spike protein, critical for the virus’s cell infection, undergoes rapid mutations, making antibodies less effective against new strains. Traditional vaccines, with their lengthy development and testing timelines, struggle to predict these evolutionary changes accurately, leading to a constant struggle to keep pace with the virus. In a study published in Science Translational Medicine, researchers from the NIH-NIAID used Bruker's Beacon® system to identify novel epitopes on the spike protein that evolve less rapidly. By sidestepping the most rapidly evolving areas, the researchers sought to discover antibodies capable of neutralizing multiple strains, including those not yet identified. https://hubs.ly/Q02nJJT00

The study presents a novel approach using dendritic-cell-targeting virus-like particles (VLPs) as carriers for mRNA vaccines. By engineering Sindbis-virus glycoproteins to recognize surface proteins on dendritic cells (DCs), the VLPs efficiently deliver mRNA encoding viral antigens. In mouse models, injection of the DC-targeting mRNA vaccine induced higher and more durable antigen-specific immune responses compared to untargeted VLPs and lipid-nanoparticle formulations. These vaccines also conferred protection against infection with SARS-CoV-2 and herpes simplex virus 1. This innovative strategy holds promise for developing potent prophylactic and therapeutic vaccines. #mRNAVaccines #DendriticCells #VirusLikeParticles 🦠💉🔬

Day 3! Let's talk cancer vaccines! A few months ago, I didn't know such a thing existed! Before we start, a vaccine is anything that trains your immune system to fight something bad. We typically get these *before* we get sick, but that’s not a requirement. With a cancer vaccine, we take it after. With cancer vaccines, the goal is the same as CAR T: teach your T cells to throw punches when they see specific proteins that are on the outside of your cancer cells. For mRNA cancer vaccines, we “sneak” something into your healthy cells that tricks them to produce a protein, which is then “dangled” outside the cell (the COVID vaccine works like this). Long story short, this attracts killer T cells and some of these become long-term memory T cells: ready for battle next time! So why aren’t mRNA cancer vaccines super prevalent? Again, I believe it’s a cost & complexity situation. We *can* make an mRNA vaccine that targets things specific to *my* cancer. In fact a German company - CEGAT - can do that for the right price. But we still have the heterogenous problem: we target 3 proteins, but miss cells inside that lack these. There is also patient-by-patient variability in immune response. For cost, we *could* make an mRNA vaccine that targets a protein that is on most cancer cells of a given cancer. Instead of making a vaccine for 1, we’re making it for 10,000 patients, for example. Savings! But do you see the problem? Sure, it’s cheaper. However, we’re now targeting fewer proteins, so the heterogenous problem will be as bad or worse: the vaccine will probably kill some of the tumor only. So in the next part, we’ll look at a different type of vaccine called a dendritic cell vaccine.

➡alpha-galactosylceramide (αGC)  is a robust agonist of iNKT cells and induces the secretion of Th1- and Th2-type cytokines. αGC and its analogs are widely used as adjuvants to enhance immune responses against viral, parasitic, and bacterial pathogens. ➡In a recent Study, Ine L. at Ghent University, Belgium have prepared Lipid Nanoparticles using αGC as adjuvant. ➡The results showed that Intramuscular (IM) vaccination with ovalbumin (OVA)-encoding mRNA encapsulated in LNPs adjuvanted with αGC showed the highest antibody- and CD8+ T cell responses. ➡Moreover, mRNA LNPs with the ionizable lipidoid C12–200 exhibited higher pro-inflammatory- and reactogenic activity compared to mRNA LNPs with SM-102, correlating with increased T cell activation and antitumor potential. ➡mRNA LNP vaccine supplemented with αGC showed synergistic protective effects against listeriosis, highlighting a key advantage of co-activating iNKT cells in antibacterial mRNA vaccines #LNP #Vaccine #mRNA #Bacterialinfection #cancer #immunity Here are the details: https://lnkd.in/e2WwDkcb

TG4050, a cancer vaccine based on Transgene's myvac platform and powered by NEC's Artificial Intelligence technologies, is designed to target neoantigens with high immunogenicity. According to data unveiled at the AACR 2024 conference, after a median follow-up period of 18.6 months, all evaluable patients who received the vaccine following standard-of-care adjuvant chemoradiotherapy (n = 16; arm A) remained in remission. In contrast, among those assigned to the observation group (n = 16; arm B), three individuals experienced disease recurrence at 6.2, 8.8, and 18.5 months, respectively. Moreover, immune responses were evaluated in 16 vaccinated patients in arm A and one vaccinated patient in arm B. Approximately 16 patients displayed activated neoantigen-specific T cells, which were absent before receiving TG4050, suggesting vaccine-induced activation. Additionally, following vaccination, the quantity of these T cells increased rapidly and remained stable for up to 7 months post-vaccination. To explore more, visit: https://lnkd.in/gVTwQqFu #TG4050 #clinicaltrials #AACR2024 #AACR2024conference #artificialintelligence #tcells #tcelltherapy #cancertherapy #cancerlcells #cancercelltherapy #cancertreatment #oncology