Andrés Venegas Arango’s Post

#molecularbiology #immunology #vaccination #vaccine From #frontier publication Platforms for #cancer #vaccine design and production focusing on "nucleic acid-based vaccines" With about 10 million deaths per year, cancer is one of the leading causes of death worldwide. For decades, one of the main goals of researchers around the world has been to find effective tools to fight cancer. In recent years, immunotherapy has emerged as an efficient strategy for cancer treatment. Stimulation of an immune response against tumor antigens is the basis for the design of anticancer vaccines. In general, cancer vaccine manufacturing platforms are classified into 4 groups: 1. Cell-based vaccines: Autologous (taken from a patient) or allogeneic (taken from another person) cells are used to produce cell vaccines. To enhance the immune response against tumor cells, tumor cell lines can be genetically modified by introducing cytokines, chemokines and genes encoding stimulatory molecules or by silencing immunosuppressive genes. A limitation of this method is that it is sometimes difficult to obtain sufficient numbers of cells to induce an effective immune response. 2. Peptide-based vaccines: These vaccines are composed of tumor-specific peptide antigens with high immunogenicity. Also, synthetic peptides are used to produce personalized cancer vaccines. With the help of this platform, vaccines for liver and cervical cancers have been produced. However, one of the main disadvantages of this vaccination approach is that the peptides do not activate the innate immune system, leading to ineffective and weak T cell responses. 3. Virus-based cancer vaccines: Many viruses are intrinsically immunogenic, and furthermore, their genetic content can be manipulated to express tumor antigens. Several viruses have been used as substrates for cancer vaccines. The most common virus-based vaccine vectors are adenoviruses, poxviruses, and alphaviruses. The negative point in relation to virus-based vaccines is the antiviral immune response that can neutralize the vector and also limit the repetition of vaccine injections. 4. Nucleic acid-based vaccines: These are vaccines that express antigens with the help of messenger DNA or RNA. Nucleic acid-based vaccine is a promising and attractive platform because it can simultaneously express multiple antigens and also induce strong MHC I-mediated CD8+ T cell responses. However, the weak immunogenicity of DNA vaccines and their long-term expression have drawn attention to RNA vaccines. Messenger RNA vaccines are an attractive and powerful immunotherapy platform against cancer due to their high immunogenicity, fast and large-scale development capability, and low production cost. MHC I molecules: are responsible for presenting peptide fragments to CD8+ T cells, which triggers an immediate immune system response against a non-self antigen. More information 👇 https://lnkd.in/dG9DafvU

Are personalized vaccines the next big thing in cancer therapy? The figure below kind of speaks for itself. The therapeutic potential for mRNA technology goes well beyond its use in vaccines for infectious diseases! Because mRNA is easy to program, it can be used for a variety of other personalized therapies. One of the most intriguing of these is to use it to eradicate cancers. This is possible because cancer cells are pretty messed up and they make a lot of weird proteins that can be recognized by the immune system! These are often referred to as ‘neoantigens.' That word might look intimidating. But don't worry, neo is just ‘New’ and antigen is ‘something that can be recognized by the immune system.’ So, how can we use these ‘neoantigens’ to coax the immune system to destroy cancer? We can make mRNAs that express them, stick them in a vaccine, and prime the immune system to then specifically recognize cancer cells! But wait, if cancer cells already express these neoantigens, why doesn’t the immune system destroy cancers without the priming? Mostly it’s because tumors start out small and don’t activate enough cells to mount a strong immune response. As tumor cells grow, the immune system sees these same antigens over and over again so it begins to tolerate them. The purpose of a cancer vaccine is to supercharge the immune system to recognize tumors as invaders! The author’s of today’s paper did just that and targeted a notoriously hard cancer to beat: Pancreatic ductal adenocarcinoma or PDAC. This cancer is lethal in 88% of patients and 90% of PDACs recur (come back) 7-9 months after surgery. So, the need for an alternative therapy is significant. In this study, patients with a PDAC that could be surgically removed were recruited and then treated with a combination of an immune checkpoint inhibitor, an individualized mRNA neoantigen vaccine, and a chemotherapy regimen. The mRNA vaccine was designed against tumor-specific neoantigens that were discovered through whole exome and RNA sequencing of the removed PDAC tissue. Ultimately, 19 patients were administered the checkpoint inhibitor, 16 went on to receive a personalized vaccine, and 15 were given the chemotherapy regimen. The overall survival and relapse free survival can be seen in (A), which in itself is a significant improvement over the current standard of care. But when broken out by vaccine responders and non-responders (B), the results are nothing short of remarkable. While only 50% of vaccine recipients responded, they were 100% relapse free beyond 18-months. Despite the small sample size of this initial study, the future of personalized cancer vaccines seems bright. And, with improved methods for neoantigen identification, hopefully we can get that responder rate closer to 100% too! ### Rojas LA et al. 2023. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. DOI:10.1038/s41586-023-06063-y

🌟 **Exciting Advances in Cancer Treatment!** 🌟 I'm thrilled to share groundbreaking news about **mRNA vaccines** and their potential impact on cancer treatment. 🎉 🔬 **How mRNA Vaccines Work:** Over the past three decades, researchers have harnessed the power of **messenger RNA (mRNA)** to create vaccines. These tiny molecules carry instructions to our cells, prompting them to produce specific proteins. In the case of mRNA cancer vaccines, the goal is to stimulate an immune response against tumor-specific proteins. 🦠🔍 🌱 **Promising Early Results:** For nearly a decade, scientists have been testing mRNA-based cancer treatment vaccines in small trials. These vaccines hold immense promise for various cancer types, including **pancreatic cancer**, **colorectal cancer**, and **melanoma**. Some trials even combine mRNA vaccines with drugs that enhance the body's immune response to tumors. 🌈 🚀 **COVID-19 Vaccine Success Accelerates Research:** The success of mRNA COVID-19 vaccines has paved the way for accelerated clinical research in cancer vaccines. Companies like **Pfizer-BioNTech** and **Moderna** drew on their experience with mRNA cancer vaccines to develop their coronavirus vaccines. Now, the same technology is being explored to combat cancer. 💪 🔍 **Ongoing Clinical Trials:** Dozens of clinical trials are underway, evaluating the safety and effectiveness of mRNA cancer vaccines. While no mRNA cancer vaccine has yet been approved by the **US Food and Drug Administration**, findings from these trials are starting to emerge. 📊 🌟 **Hope on the Horizon:** Imagine a future where personalized mRNA vaccines empower our immune systems to target cancer cells directly. It's a beacon of hope for patients and their families. 🌅 Let's continue supporting research, spreading awareness, and celebrating scientific breakthroughs! 🙌 #CancerResearch #mRNAVaccines #HopeForTheFuture *P.S. Feel free to share this post—it might reach someone who needs it!* 🤝 Source: (1) How mRNA Vaccines Might Help Treat Cancer - NCI. https://lnkd.in/erxPMr6f. (2) An mRNA vaccine to treat pancreatic cancer | National Institutes of .... https://lnkd.in/e_bcQW4n. (3) Can mRNA vaccines be used in cancer care?. https://lnkd.in/eNYzGrxM. (4) How mRNA Vaccines Help Fight Cancer Tumors, Too. https://lnkd.in/eKZzuTHN.

Cancer vaccines are a type of immunotherapy designed to stimulate the body's immune system to recognize and attack cancer cells. Unlike traditional vaccines that prevent infectious diseases by training the immune system to recognize and destroy pathogens like viruses or bacteria, cancer vaccines are used to treat existing cancer or prevent its recurrence by targeting specific cancer cells or proteins. There are different approaches: *Preventive (Prophylactic) Vaccines: These vaccines are designed to prevent certain types of cancer from developing. For example, the human papillomavirus (HPV) vaccine can prevent infections with HPV types that cause cervical cancer, anal cancer, and other cancers. *Therapeutic (Treatment) Vaccines: These vaccines are used to treat existing cancer by stimulating the immune system to recognize and attack cancer cells. Therapeutic cancer vaccines are often designed to target specific antigens (proteins) found on cancer cells, triggering an immune response against those cells. *Personalized Cancer Vaccines: These vaccines are tailored to the individual patient based on their specific cancer cells. Personalized cancer vaccines, also known as neoantigen vaccines, are designed to target unique mutations or proteins present on the surface of an individual's cancer cells. Cancer vaccines can be made from a variety of substances, including cancer cells, proteins, DNA, or RNA. Some vaccines are made using cancer cells that have been modified in the laboratory to produce certain proteins that can stimulate the immune system. Others may contain specific antigens or genetic material from cancer cells. Lin, M.J., Svensson-Arvelund, J., Lubitz, G.S. et al. Cancer vaccines: the next immunotherapy frontier. Nat Cancer 3, 911–926 (2022). https://lnkd.in/gHdk6XUh https://lnkd.in/gb46YZ3w #knowledgesharing #fightagainstcancer #personalisedtherapy #precisiononcology "Disclaimer: The views and opinions expressed in this post are solely those of the author and do not necessarily reflect the official policy or position of any organization or company mentioned. The information provided in this post is for educational and knowledge-sharing purposes only and should not be construed as professional advice. Readers are encouraged to consult with relevant experts or professionals in their respective fields before making any decisions based on the information provided. The author makes no representations or warranties regarding the accuracy, completeness, or reliability of any information shared in this post. Participation in discussions or engagement with the content shared in this post is voluntary and at the reader's own risk. The author assumes no liability for any errors, omissions, or inaccuracies in the content of this post or for any damages or losses arising from its use or reliance upon."

𝐋𝐞𝐚𝐫𝐧 𝐦𝐨𝐫𝐞 𝐚𝐛𝐨𝐮𝐭 𝐂𝐚𝐧𝐜𝐞𝐫 𝐕𝐚𝐜𝐜𝐢𝐧𝐞𝐬 Cancer vaccines represent a promising frontier in the field of oncology, aiming to harness the body’s immune system to recognize and destroy cancer cells. Unlike traditional vaccines that prevent infectious diseases by priming the immune system against specific pathogens, cancer vaccines are designed to target abnormal proteins or antigens expressed by cancer cells. 𝐂𝐥𝐢𝐜𝐤 𝐇𝐞𝐫𝐞 𝐭𝐨 𝐆𝐞𝐭 𝐅𝐫𝐞𝐞 𝐏𝐃𝐅 𝐁𝐫𝐨𝐜𝐡𝐮𝐫𝐞: https://lnkd.in/gGrs6w5z There are two main types of cancer vaccines: preventive (prophylactic) vaccines and therapeutic vaccines. 1. Preventive Vaccines: These are administered to individuals without cancer to prevent certain types of cancers caused by infections. A notable example is the Human Papillomavirus (HPV) vaccine, which protects against HPV #infections that can lead to cervical and other cancers. Another example is the Hepatitis B vaccine, which prevents liver cancer associated with chronic Hepatitis B infections. 2. Therapeutic Vaccines: These are designed for patients who already have cancer. Therapeutic cancer vaccines work by stimulating the immune system to recognize and attack cancer cells more effectively. They can be made from a variety of substances, such as cancer cells, parts of cancer cells, or antigens specific to cancer cells. By presenting these antigens to the immune system, either alone or in combination with immune-stimulating substances called adjuvants, #therapeutic vaccines aim to train the immune system to recognize and destroy cancer cells throughout the body. Despite the promise of cancer vaccines, developing effective ones has proven challenging. Cancer cells can evade detection by the immune system in various ways, and tumors often create a suppressive microenvironment that hinders immune responses. Researchers are continually exploring new strategies to enhance the efficacy of cancer vaccines, such as combining them with other treatments like immune checkpoint inhibitors or targeted therapies. Currently, therapeutic cancer vaccines are being studied in #clinical trials for various types of cancer, including melanoma, prostate cancer, and lung cancer. While some vaccines have shown promising results in certain patient populations, more research is needed to understand their long-term effectiveness, safety profiles, and potential side effects. Cancer vaccines represent a personalized approach to cancer treatment and prevention, leveraging the body’s own defenses against this complex disease. Continued research and development in this field hold the potential to revolutionize cancer care by offering new options for patients across different stages of the disease. #Cancertherapeutics #Cancer #therapeutics #market #health #innovation #pharma

A vaccine for breast cancer? Breast cancer surpassed lung cancer in 2020 to claim the title of most prevalent form of cancer worldwide, according to the WHO. A friend texted me last night asking for my thoughts on breast cancer vaccine research. I was not familiar enough with the topic to comment, so I grabbed a coffee this morning and sat down to see what I could find. Vaccines work by mimicking a virus, which helps our bodies build up an immune response so that when we are infected with the virus, our immune system goes to work quickly and effectively. Cancer is different from a virus as it arises from our own cells, whereas a virus is a foreign invader. Our immune system does not recognize cancer as a troublemaker and does nothing to help fight it. Over the last couple of decades, there has been work on creating specific tumor-specific antigens so that the immune system can recognize cancer as something it should protect us from. The most recent work uses the same mRNA delivery system utilized by the COVID-19 vaccines. Without getting too deep into it 🤓 , mRNA stands for messenger ribonucleic acid. RNA is present in all living cells and carries genetic information that tells cells how to make proteins. When used in a vaccine, mRNA is coded for a specific disease antigen and teaches our bodies how to make copies of it. This way, our immune system learns to recognize it and mount a defense. In short, when compared to traditional vaccines, using mRNA is a faster, less expensive, and safer way to produce vaccines. For cancer vaccines, in particular, mRNA offers’ more diverse target options. The University of Washington’s Cancer Vaccine Institute recently published a study (in JAMA Oncology) showing promising results. Their data comes from a study looking at advanced-stage HER2+ breast cancer patients. Although the outcomes of their study do raise hope, it was a very small phase 1 study (66 women), so we need to be cautious in our excitement. Research is looking promising. I believe that within my lifetime, we will be utilizing breast cancer vaccines in some capacity, most likely as a treatment, not as a prevention. I hope these studies receive the funding and support needed for the amazing work they are pioneering. What are your thoughts on the future of vaccines? 👇

Virogin Biotech announced its publication detailing a new generation mRNA therapeutic vaccine for HPV-related tumors in Immunology. Through selective targeting and activation of antigen-presenting cells, our self-adjuvant vaccine M22H04 achieves efficient activation of anti-tumor immunity, leading to complete tumor regression and prevented tumor recurrence. Our vaccine encodes two modified oncoproteins, E6 and E7, fused with an antigen-presenting cell (APC)-targeting immunogen within the LNP-encapsulated mRNA vaccine. For more details, you can read the full article on Virogin's website here: https://lnkd.in/dsJ6wvMu   The study emphasizes the effectiveness of mRNA technology in cancer vaccine development over traditional vaccines. Virogin’s research in mRNA therapeutic vaccines underscores its capability to develop potent vaccines and highlights how its deep understanding of immunology contributes to pioneering vaccine approaches.   #HPV #CancerVaccine #mRNATherapeuticVaccine #Immunotherapy #mRNA #Vaccines #Women’sHealth

Differentiating Between DNA and mRNA Platforms By John Parkinson The Wistar Institute in Philadelphia, Pa, is involved in cancer, immunology and infectious disease research and vaccine development. The research center advances basic research, translating fundamental discoveries into future therapies to benefit global health and training the next generation of scientific leaders. Ami Patel, PhD, assistant professor, Vaccine & Immunotherapy Center, Wistar Institute, leads a laboratory team at the center. A major area of study with her team has been around employing non-viral DNA vectors for vaccine and antibody delivery. Patel’s most recent studies include DNA vaccine development against Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and multiple studies in the rapidly advancing field of DNA-encoded monoclonal antibodies (DMAbs). Of course, everyone is familiar with the mRNA platform from the pandemic and the subsequent COVID-19 vaccines. However, not much is known to the public about how DNA vaccines and monoclonal antibodies work. “DNA itself is a very inherently stable molecule. It has a very large coding capacity, and so that allows us to put very large synthetic genes inside DNA,” Patel said. “mRNA is really kind of an in-between step between DNA and protein synthesis. And when you have an mRNA platform, you get very rapid protein production. It's kind of an in-between way to kick start that process. And so, it's very rapid; it's a very burst of expression. But then it's finished with synthetic DNA. It mostly takes place in the nucleus, and you get multiple copies of mRNA coming off of that DNA molecule. And so, you can have a longer period of expression, and a longer period of protein expression afterwards, following translation. This allows us to encode genes in a different way and to get different types of immune responses, for example, or different types of protein production than you would get from a short burst from an mRNA platform.” One of the interesting differences in DNA and mRNA is that the former is temperature stable, and it allows it to be used internationally more easily. “Being temperature stable, it helps enable some of these properties for delivery to resource limited settings, such as low and middle income countries, because it doesn't necessarily have to have the cold chain that's attached to it like mRNA,” she said. Patel spoke at last week’s World AMR Congress, and her presentation, “Tackling Pandemic Pathogens: Gene-Encoded Antibodies as Pre-Exposure Prophylaxis,” discussed some of her work around the DNA platform. Click on image in banner below to finish reading this piece and to watch the interview. Posted by Larry Cole Executive Director of Covid Impact 360

#Cancer #Vaccines from an #Immunology Perspective | Shania Makker et al Review the State-of-the-Art Focusing on #DendriticCells as #Orchestrators of anti-#Tumour #Immunity 👍 | OPEN ACCESS at #Immunotherapy Advances | British Society for Immunology The concept of a therapeutic cancer vaccine to activate anti-tumour immunity pre-dates innovations in checkpoint blockade immunotherapies. However, vaccination strategies have yet to show the hoped-for successes in patients, and unanswered questions regarding the underlying immunological mechanisms behind cancer vaccines have hampered translation to clinical practice. Recent advances in our understanding of the potential of tumour mutational burden and neo-antigen-reactive T cells for response to immunotherapy have re-ignited enthusiasm for cancer vaccination strategies, coupled with the development of novel mRNA-based vaccines following successes in prevention of COVID-19. Here*, Shania Makker, Charlotte Galley & Clare Bennett summarise current developments in cancer vaccines and discuss how advances in our comprehension of the cellular interplay in immunotherapy-responsive tumours may inform better design of therapeutic cancer vaccines, with a focus on the role of dendritic cells as the orchestrators of anti-tumour immunity. The increasing number of clinical trials and research being funnelled into cancer vaccines has demonstrated the ‘proof-of-principle’, supporting the hypothesis that therapeutic vaccines have potential as an immuno-oncology agent. For efficacious and safe cancer vaccines to be developed, better understanding of the underpinning immunological mechanisms is paramount. *https://lnkd.in/d8M6vCF7 Celentyx Ltd #immunooncology www.celentyx.com Professor Nicholas Barnes PhD, FBPhS Omar Qureshi Catherine Brady SCHEMATIC | Targeting DCs to enhance therapeutic cancer vaccines | Our increased understanding of the role of DCs in anti-tumour immunity may inform opportunities for intervention: (1) vaccine-mediated delivery of antigens to DCs and activation of migration to LNs; (2) enhanced priming of naïve tumour-reactive T cells. Antigen presentation to Tcf1+CD8+ T cells may augment the pool of circulating effector T cells that are sensitive to immune checkpoint inhibition; (3) interventions that directly increase intra-tumoural DC activity (frequency, antigen presentation, activation) to re-invigorate exhausted T cells, probably in the presence of checkpoint inhibition |

MIRROR REFLECTION: THERAPEUTIC CANCER VACCINE INSANITY Albert Einstein famously said: “Insanity is doing the same thing over and over again and expecting different results.” Therapeutic cancer vaccines against existing cancers have repeatably demonstrated disappointing results in the clinic. Mirror Biologics’ StimVax cancer vaccine protocol represents a new immunologically rational approach to therapeutic cancer vaccines against progressive metastatic disease. Whereas, the design of past therapeutic vaccines against this indication may be the definition of immunological insanity. When a neoplasm forms, it is exposed to the immune system. The development of metastatic cancer is a failure of the immune system to properly surveille and protect against cancer growth and spread. The re-introduction of the same tumor or tumor component formulated as a vaccine to the same failed immune system (e.g., through introduction of adjuvanted tumor lysates, tumor-derived proteins, tumor antigen coding DNA/RNA) has not surprisingly mostly resulted in failed immune control. The underlying hypothesis driving therapeutic cancer vaccine design is that cancer is a disease of a weak immune system, therefore boosting the immune response to the cancer should be therapeutic. Re-introducing the existing cancer to the immune system with immune-boosting adjuvants or by administering adoptively transferred or linker conjugated innate cells (e.g., NK, gamma-delta T-cells, LAK, CIK), or genetically-manipulated targeted effector cells (e.g., CAR-T, CAR-NK, CAR-Mac), hoping that the new introduction of the cancer to the immune system will result in a more effective response is immunological insanity. Further, re-introduction of cancer is complicated by immune editing, making existing cancer less immunogenic than the original. Further, existing disease usually contains significant intratumoral heterogeneity with genetically diverse cell clusters. A more rational immunological approach might be to first ‘modulate’ the failed immune response to prime for an effective immune response upon tumor re-introduction. StimVax is designed to first modulate the failed immune response of a cancer patient from an ineffective Th2-dominant response to an effective Th1-dominated response. Tumor neo-antigens are then re-introduced by activating innate immune cell tumor lysis. A variety of other methods could also be used after immune modulating therapy to elicit tumor-specific immunity, including radiation, certain types of chemotherapy, ablation technologies, bi-specific linker technologies, with or without adoptive cell transfer, and genetically-manipulated targeted innate and effector immune cells. StimVax is currently being evaluated in a Phase IIB clinical study in chemotherapy- and immunotherapy-refractory metastatic colorectal cancer and in a Phase II/III randomized controlled study in advanced/metastatic, high risk liver cancer. #immunotherapy #immunooncology