Neoantigen therapy

Extracted Attributes

• Estimated Cost

  $500,000 (half a million USD)

• Scientific Field

  Oncology / Cancer Immunotherapy

• Primary Modalities

  Individualized mRNA vaccines, adoptive T-cell therapy (neoACT), TCR-engineered T cells

• Mechanism of Action

  Induces adaptive immune responses specifically against novel mutated proteins (neoantigens) unique to tumor cells

• Limitations and Challenges

  Complex and time-consuming genomic profiling, high manufacturing costs, technically demanding cell expansion, and market access issues

Timeline

• Moderna publishes an update on exploring individualized neoantigen therapies (INTs) developed in collaboration with Merck using mRNA technology. (Source: https://www.modernatx.com/media-center/all-media/blogs/individual.neoantigen-therapies)

  2023-06-05

Antigen

In immunology, an antigen (Ag) is a molecule, or portion thereof, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. Antigens can be proteins, peptides (amino acid chains), polysaccharides (chains of simple sugars), lipids, or nucleic acids. Antigens exist on normal cells, cancer cells, parasites, viruses, fungi, and bacteria. Antigens are recognized by antigen receptors, including antibodies and T-cell receptors. Diverse antigen receptors are made by cells of the immune system so that each cell has a specificity for a single antigen. Upon exposure to an antigen, only the lymphocytes that recognize that antigen are activated and expanded, a process known as clonal selection. In most cases, antibodies are antigen-specific, meaning that an antibody can only react to and bind one specific antigen; in some instances, however, antibodies may cross-react to bind more than one antigen. The reaction between an antigen and an antibody is called the antigen-antibody reaction. Antigen can originate either from within the body ("self-protein" or "self antigens") or from the external environment ("non-self"). The immune system identifies and attacks "non-self" external antigens. Antibodies usually do not react with self-antigens due to negative selection of T cells in the thymus and B cells in the bone marrow. The diseases in which antibodies react with self antigens and damage the body's own cells are called autoimmune diseases. Vaccines are examples of antigens in an immunogenic form, which are intentionally administered to a recipient to induce the memory function of the adaptive immune system towards antigens of the pathogen invading that recipient. The vaccine for seasonal influenza is a common example.

Web Search Results

• What is neoantigen-based therapy?

  ## Neoantigen-targeted T cell therapy Neoantigen-targeted T cell therapy is a type of T cell therapy in which T cells are collected from the patient – either from the blood or directly from a tumor sample. From these T cells, naturally occuring T cells that have T cell receptors (TCRs) that recognize neoantigens can be isolated. Then, in the lab, these cells can be strengthened and increased in numbers before being given back to the patient as a living drug. The T cells then continue to multiply within the patient, where they recognize neoantigens and kill cancer cells. [...] Both tumor-associated antigens and neoantigens can serve as good targets for immunotherapy, however, neoantigens may be the stronger choice. Neoantigens are more likely than tumor-associated antigens to trigger a strong immune response, as they are entirely unfamiliar to the body – like the proteins of a virus or bacteria are – and easily stand out as molecules that do not belong. Further, while tumor-associated antigens may be found at low levels elsewhere in the body, neoantigens are completely unique to the cancer cells, so targeting neoantigens for immunotherapy comes with a lower risk of accidentally harming healthy cells along the way. For these two reasons – triggering stronger immune responses and being present only in cancer cells – neoantigens have become a preferred target for [...] In other cases, researchers may use T cell receptor (TCR) engineering to force T cells to target neoantigens. For TCR engineering, T cells are collected from a patient’s blood and a gene is added to code for a T cell receptor that recognizes a neoantigen that is known to be present in the patient’s cancer. These TCR-engineered T cells can then be grown and multiplied in the lab to form a massive T cell army that can be delivered back to the patient. When the engineered T cells are delivered back into the patient, they hunt down and attack any cells containing the neoantigens, leading them directly to cancer cells. T cell receptor engineering is currently focused on shared neoantigens, though researchers hope to one day apply it to personal neoantigens.

• Individualised Neoantigen Therapy (INT) - Melanoma Focus

  ## Individualised Neoantigen Therapy (INT) ### What is an Individualised Neoantigen Therapy (INT)? An individualised neoantigen therapy or INT uses a persons’ own melanoma cells to create a treatment that can help their body’s natural defence (immune system) to recognise, attack and kill their melanoma. This is known as a personalised cancer treatment because it identifies and adapts the specific characteristics of a person’s cancer to try to make an effective treatment for them. These treatments are personalised cancer vaccines. DNA ### How do INTs work? [...] Receiving an individualised neoantigen therapy involves several steps. First, a sample of a person’s melanoma is collected and analysed to identify genetic changes that can give rise to neoantigens that may be recognised by the immune system. The information from the analysis is then used to design and manufacture an individualised treatment specifically for that person. Once the treatment has been manufactured, it is given to the person as an injection. The exact process and timing can vary, depending on the INT being studied and the clinical trial. ### What are the potential benefits and side effects of INT?

• Individualized Neoantigen Therapies

  Cancer cells express abnormal proteins, or neoantigens, that are not usually seen in normal cells. These cancer proteins make up a patient’s cancer “fingerprint.” Individualized neoantigen therapies are designed with the goal of specifically matching one patient's unique cancer fingerprint. The goal of individualized neoantigen therapies is to train a patient's immune cells to recognize the cancer fingerprint proteins and launch an immune response against the cancer cells. Individualized neoantigen therapies are currently being studied in clinical trials. As of today, there are currently no FDA-approved individualized neoantigen therapies. How are Investigational mRNA Individualized Neoantigen Therapies Made? [...] The process to make our individualized neoantigen therapy starts in the clinic, where a study participant has their blood drawn and their tumor biopsied. Sequencing is then performed in a lab to compare data from the tumor biopsy sample and the study participant’s healthy blood cells, which are not mutated, to identify the unique genetic mutations of that individual’s cancer. [...] Blogs / Exploring One Medicine for One Patient... 05 June 2023 # Exploring One Medicine for One Patient: Individualized Neoantigen Therapies By Michelle Brown, VP, INT Oncology Each person’s cancer is different because cancer cells have genetic mutations that make them unique, which can make the cancer difficult to treat. That's why we, in collaboration with Merck, are researching mRNA medicines that are designed specifically for an individual patient. Individualized neoantigen therapies (INTs) are an innovative approach that tailor treatment to each patient's individual cancer.

• Neoantigen cancer vaccines: a new star on the horizon | Cancer Biology & Medicine

  ### Neoantigen-targeted adoptive T cell therapy Neoantigen-targeted adoptive cell therapy (neoACT) is an innovative and personalized approach to cancer treatment that harnesses the power of the immune system to specifically target and eliminate cancer cells. Various strategies have been used, such as the selection of neoantigen-reactive T cells and engineering of TCRs to target neoantigen-specific T cells (neoTCR-T cells). The original T cells can be obtained by harvesting TILs from the tumor or enriching lymphocytes from peripheral blood mononuclear cells (PBMCs). The neoantigen-targeting T cells are then expanded ex vivo and infused back into the patient, where the neoantigen-targeting T cells selectively recognize and attack cancer cells expressing targeted neoantigens. [...] Neoantigen-targeted CAR-T cell therapy involves modifying T cells to express chimeric antigen receptors (CARs) that recognize antigens directly through CARs approaches independent of HLA restriction, but only specific surface antigens on cancer cells are targeted, such as unmodified proteins, glycoproteins, glycolipids, and carbohydrates. An example of neoantigen-targeted CAR-T therapy in solid tumors is a neoantigen derived from EGFRvIII mutations, which is caused by the in-frame deletion of exons 2–7 deletions in 30% of newly diagnosed glioblastoma patients, making the neoantigen derived from EGFRvIII mutations an ideal target for CAR-T therapy68. In contrast, TCRs have evolved to recognize epitopes derived from the entirety of the proteome, including cell surface, cytosolic, and [...] Overall, neoantigen-targeted ACT represents a cutting-edge approach to cancer immunotherapy and has shown promising results in early clinical trials for various types of cancers, including melanomas, lung cancer, and colorectal cancer. Neoantigen-targeted ACT offers the potential for improved treatment outcomes and long-term survival for patients with advanced or refractory cancers. By leveraging the unique neoantigens present on cancer cells, this therapy has the potential to provide personalized and effective treatment options for patients with various cancers. Identifying neoantigens can be complex and time-consuming, requiring sophisticated genomic analysis. Additionally, the large-scale production of neoantigen-specific T cells can be technically demanding and expensive. Further

• Neoantigen-directed therapeutics in the clinic: where are we?

  by L Lybaert · 2023 · Cited by 33 — Neoantigen-driven therapeutics specifically redirect the immune system of the patient to enable or reinduce its ability to recognize and eliminate cancer cells.