mRNA cancer vaccine

Extracted Attributes

• Therapy Type

  Therapeutic Cancer Vaccine / Personalized Neoantigen Therapy

• Estimated Cost

  Approximately $500,000 per therapy

• Scientific Field

  Oncology / Cancer Immunotherapy

• Target Indications

  Cutaneous melanoma, non-small cell lung cancer, colorectal cancer, esophageal cancer, and pancreatic cancer

• Mechanism of Action

  Encodes patient-specific tumor neoantigens to trigger immunosurveillance and antigen-specific T-cell responses

• Clinical Limitations

  Requires individualized manufacturing; monotherapy may struggle against immunosuppressive tumor microenvironments

• Primary Delivery Mechanism

  Lipid nanoparticles (LNPs) and ex-vivo engineered dendritic cells

• Estimated Production Turnaround

  1 to 2 months from tumor biopsy collection

Timeline

• The first mRNA-based cancer vaccine study tests dendritic cells pulsed with RNA in vitro. (Source: PubMed Central (PMC9512276))

  1996-01-01

• Moderna enters a strategic collaboration with Merck & Co. to develop personalized mRNA cancer vaccines in combination with Keytruda. (Source: Chemical & Engineering News)

  2018-01-01

• Moderna and Merck advance the combination of personalized mRNA cancer vaccine mRNA-4157 and Keytruda into Phase III clinical trials. (Source: International Journal of Oncology (PMC11251742))

  2023-07-01

Cancer vaccine

A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient. The immune system normally destroys cancer cells in a process called immunosurveillance. However, cancers can adapt to evade the immune system. Tumors form when the immune system fails to destroy cancer cells and they are able to multiply. Some types of cancer, such as cervical cancer and liver cancer, are caused by viruses (oncoviruses). Traditional vaccines against those viruses, such as the HPV vaccine and the hepatitis B vaccine, prevent those types of cancer. Other cancers are to some extent caused by bacterial infections (e.g. stomach cancer and Helicobacter pylori). Traditional vaccines against cancer-causing bacteria (oncobacteria) are not further discussed in this article.

Web Search Results

• In a first, an mRNA cancer vaccine succeeds in late-stage ...

  A personalized messenger RNA (mRNA) cancer vaccine slowed the return and spread of melanoma when used alongside Merck & Co.’s checkpoint inhibitor Keytruda in a first for the nascent cancer vaccine space. Moderna, which developed the vaccine, announced the results in a joint press release with Merck on Wednesday. The drugmakers have not released detailed data, but they will present them at an upcoming medical conference. Moderna’s vaccine, intismeran, is a personalized neoantigen vaccine. It delivers mRNA that encodes tumor-specific mutations identified from a person’s previously removed tumor. That mRNA is bundled into a lipid nanoparticle before being delivered back into a patient to train their body to fight the tumor cells. [...] “These Phase 3 findings represent a pivotal moment for the field of cancer research. For many years, the idea of creating an mRNA treatment designed specifically for an individual patient's cancer was aspirational. We are now helping turn that vision into a reality,” Moderna CEO Stéphane Bancel says in the announcement. Moderna signed a partnership with Merck in 2018 to develop an mRNA vaccine to be used in combination with Keytruda. The first mRNA vaccines to be approved for use in humans were the COVID-19 vaccines, developed by Moderna and BioNTech/Pfizer. But scientists have long hoped that the technology could be used for personalized cancer treatments. Moderna and Merck say today’s results mark the first positive Phase 3 readout for a cancer vaccine.

• Clinical advances of mRNA vaccines for cancer immunotherapy

  The development of mRNA vaccines represents a significant advancement in cancer treatment, with more than 120 clinical trials to date demonstrating their potential across various malignancies, including lung, breast, prostate, melanoma, and more challenging cancers such as pancreatic and brain tumors. These vaccines work by encoding tumor-specific antigens and immune-stimulating molecules, effectively activating the immune system to target and eliminate cancer cells. Despite these promising advancements, significant challenges remain, particularly in achieving efficient delivery and precise regulation of the immune response. This review provides a comprehensive overview of recent clinical progress in mRNA cancer vaccines, discusses the innovative strategies being employed to overcome

• Clinical advances and ongoing trials of mRNA vaccines for cancer treatment

  Two lipid nanoparticle mRNA cancer vaccines encoding several neoantigens (mRNA-4157) are being assessed in combination with pembrolizumab as adjuvant therapy in patients with high-risk cutaneous melanoma following complete resection (NCT03313778 and NCT03897881). The same vaccine template (mRNA-4157) was examined as a monotherapy in patients with completely resected solid tumours (NCT03313778), and in combination with pembrolizumab in patients with unresectable solid tumours. The treatment induced neoantigen-specific T cells and did not lead to serious adverse events (grade 3 or worse). 13 patients received mRNA-4157 monotherapy, and all patients except one remained free of cancer on study treatment, with a median follow-up of 8 months. Of the 19 evaluable patients receiving combination [...] ## . Most mRNA-based cancer vaccines are therapeutic rather than prophylactic, and require multiple administrations and substantial vaccine potency to induce a tumour response when given as monotherapy. Monotherapy mRNA-based vaccines could be an effective treatment for patients diagnosed with early-stage cancer or in an adjuvant setting, but it appears unlikely that the vaccines will succeed as a monotherapy treatment for advanced cancers because of challenges regarding the highly immunosuppressive tumour microenvironment of this setting. [...] In 1996, the first mRNA-based cancer vaccine study tested dendritic cells pulsed with RNA in vitro.8 Nowadays, technological advances have led to optimised mRNA structure, stability, and delivery methods, and multiple clinical trials are now enrolling patients with cancer for mRNA-based vaccine treatments (Table 1, Table 2 ).2, 3 mRNA vaccine administration routes include intradermal, subcutaneous, intranasal, intranodal, intramuscular, intratumoural, and intravenous delivery.9 The ex-vivo engineering of autologous dendritic cells with mRNA has been the method of choice for tumour antigen delivery, but most mRNA vaccine approaches focus on direct mRNA administration using lipid nanoparticulate formulation carriers (table 1).Table 1ClinicalTrials.gov-registered mRNA-based cancer vaccine

• How mRNA Vaccines Might Help Treat Cancer - NCI

  Dozens of clinical trials are testing mRNA treatment vaccines in people with various types of cancer, including pancreatic cancer, colorectal cancer, and melanoma. Some vaccines are being evaluated in combination with drugs that enhance the body’s immune response to tumors. But no mRNA cancer vaccine has been approved by the US Food and Drug Administration for use either alone or with other cancer treatments. “mRNA vaccine technology is extremely promising for infectious diseases and may lead to new kinds of vaccines,” said Elad Sharon, M.D., M.P.H., of NCI's Division of Cancer Treatment and Diagnosis. “For other applications, such as the treatment of cancer, research on mRNA vaccines also appears promising, but these approaches have not yet proven themselves.” [...] ## Developing and testing personalized mRNA cancer vaccines For more than a decade, cancer researchers have been developing a type of treatment known as a personalized cancer vaccine using various technologies, including mRNA and protein fragments, or peptides. The investigational mRNA vaccines are manufactured for individuals based on the specific molecular features of their tumors. It takes 1 to 2 months to produce a personalized mRNA cancer vaccine after tissue samples have been collected from a patient. “Speed is especially important for individualized cancer vaccination,” said Mathias Vormehr, Ph.D., codirector of Cancer Vaccines at BioNTech. “A highly individualized vaccine combination must be designed and produced within weeks of taking a tumor biopsy.” [...] As stunningly successful as the mRNA COVID-19 vaccines have been, researchers have long hoped to use mRNA vaccines for a very different purpose—to treat cancer. mRNA-based cancer treatment vaccines have been tested in small trials for nearly a decade, with some promising early results. In fact, scientists at both Pfizer-BioNTech and Moderna drew on their experience developing mRNA cancer vaccines to create their coronavirus vaccines. Now, some investigators believe the success of the mRNA COVID-19 vaccines could help accelerate clinical research on mRNA vaccines to treat cancer.

• mRNA vaccine development and applications: A special focus on tumors (Review)

  ### Esophageal cancer A study of a personalized mRNA cancer vaccine combined with a PD-1 inhibitor for the treatment of advanced esophageal squamous cell carcinoma was recently reported (149). The patient enrolled in the study was first screened for neoantigens using whole-transcriptome sequencing of tissue samples from the lesion. A personalized mRNA cancer vaccine was developed that was tailored to these neoantigens. Subsequently, the patient was administered the mRNA cancer vaccine in combination with a PD-1 inhibitor and the patient obtained partial remission; the safety of the treatment regimen was within manageable limits. Thus, mRNA vaccines may be an effective therapeutic strategy for patients with advanced esophageal cancer. [...] ## . Since then, the use of mRNA vaccines in cancer treatment has been investigated in several preclinical and clinical investigations. A small number of mRNA cancer vaccine clinical studies have been conducted so far (122). The majority of trials have focused on acute myeloid leukemia (AML) (123), multiple myeloma (124), mesothelioma (125), glioblastoma (126), malignant glioma (127) and renal cell carcinoma (128), as well as mRNA vaccines for pancreatic cancer (129), melanoma (130), BCa (131), non-small cell lung cancer (132), prostate cancer (133), ovarian cancer (134) and colorectal cancer (135) and are still in their early stages (I and II) (136-140) (Fig. 5). Moderna and Merck Sharp & Dohme announced that the first combination therapy of an mRNA personalized cancer vaccine [...] combination therapy of an mRNA personalized cancer vaccine (mRNA-4157) and an anti-programmed cell death 1 (PD-1) monoclonal antibody (Keytruda) advanced to phase III clinical trials in July 2023 (14). This was the first mRNA cancer vaccine to enter phase III clinical trials. Table I summarizes the clinical trials of mRNA vaccines for the treatment of cancer.