Personal neoantigen cancer vaccines: The momentum builds.
Ontology highlight
ABSTRACT:
SUBMITTER: Fritsch EF
PROVIDER: S-EPMC4121338 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Personal neoantigen cancer vaccines: The momentum builds.
Fritsch Edward F EF Hacohen Nir N Wu Catherine J CJ
Oncoimmunology 20140625
Neoantigen-based cancer vaccines designed to target the unique immunogenic mutations arising in each patient's tumor are breathing new life into a struggling approach. Data continue to demonstrate the importance of neoantigens in immune control of cancer. Despite manufacturing complexity, outstanding questions and desired further improvements, neoantigen vaccines are currently undergoing clinical evaluation. ...[more]
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Project description:Personal Neoantigen Cancer Vaccines
| PRJNA401959 | ENA
Project description:BackgroundIt is widely hoped that personal cancer vaccines will extend the number of patients benefiting from checkpoint and other immunotherapies. However, it is clear creating such vaccines will be challenging. It requires obtaining and sequencing tumor DNA/RNA, predicting potentially immunogenic neoepitopes and manufacturing a one-use vaccine. This process takes time and considerable cost. Importantly, most mutations will not produce an immunogenic peptide and many patient's tumors do not contain enough DNA mutations to make a vaccine. We have discovered that frameshift peptides (FSP) created from errors in the production of RNA rather than from DNA mutations are potentially a rich source of neoantigens for cancer vaccines. These errors are predictable, enabling the production of a FSP microarray. Previously we found that these microarrays can identify both personal and shared neoantigens. Here, we compared the performance of personal cancer vaccines (PCVs) with that of a shared antigen vaccine, termed Frameshift Antigen Shared Therapeutic (FAST) vaccine, using the 4 T1 breast cancer model. Sera from 4 T1-tumor bearing mice were assayed on the peptide microarray containing 200 Fs neoantigens, for the PCV, the top 10 candidates were select and personal vaccines constructed and administrated to the respective mice. For the FAST, we selected the top 10 candidates with higher prevalence among all the mice challenged. Seven to 12 days challenged mice were immunized, combined or not with immune checkpoint inhibitor (ICI) (αPD-L1 and αCTLA-4). Primary and secondary tumor clearance and growth were evaluated as well as cellular and humoral immune response against the vaccine targets by IFN-γ ELISPOT and ELISA. Lastly, we analyzed the immune response of the FAST-vaccinated mice by flow cytometry in comparison to the control group.ResultsWe found that PCVs and FAST vaccines both reduced primary tumor incidence and growth as well as lung metastases when delivered as monotherapies or in combination with ICI. Additionally, the FAST vaccine induces a robust and effective T-cell response.ConclusionsThese results suggest that FSPs produced from RNA-based errors are potent neoantigens that could enable production of off-the-shelf shared antigen vaccines for solid tumors with efficacy comparable to that of PCVs.
| S-EPMC7201681 | biostudies-literature
Project description:Cancer vaccines have encountered their ideal personalized partner along with evidence for great breakthroughs in the identification and synthesis of neoantigens. Individual cancer neoantigen vaccines are capable of eliciting robust T-cell responses and have been demonstrated to achieve striking clinical efficacy due to their high immunogenicity and central thymic tolerance escape of neoantigens. Two recent phase I clinical trials have provided support for the hypothesis and have heralded a nascent era of personalized vaccines in the field of immunotherapy. This review aims to address the identification of neoepitopes and describes advances made in personalized vaccines. In addition, this review discusses the challenges related to the exploitation of vaccine therapy, and provides potential thoughts for the improvement of vaccine design and applications.
| S-EPMC6096398 | biostudies-literature
Project description:Neoantigen vaccines are based on epitopes of antigenic parts of mutant proteins expressed in cancer cells. These highly immunogenic antigens may trigger the immune system to combat cancer cells. Improvements in sequencing technology and computational tools have resulted in several clinical trials of neoantigen vaccines on cancer patients. In this review, we have looked into the design of the vaccines which are undergoing several clinical trials. We have discussed the criteria, processes, and challenges associated with the design of neoantigens. We searched different databases to track the ongoing clinical trials and their reported outcomes. We observed, in several trials, the vaccines boost the immune system to combat the cancer cells while maintaining a reasonable margin of safety. Detection of neoantigens has led to the development of several databases. Adjuvants also play a catalytic role in improving the efficacy of the vaccine. Through this review, we can conclude that the efficacy of vaccines can make it a potential treatment across different types of cancers.
| S-EPMC9947792 | biostudies-literature
Project description:Cancer immunotherapies are treatments that use drugs or cells to activate patients' own immune systems against cancer cells. Among them, cancer vaccines have recently been rapidly developed. Based on tumor-specific antigens referred to as neoantigens, these vaccines can be in various forms such as messenger (m)RNA and synthetic peptides to activate cytotoxic T cells and act with or without dendritic cells. Growing evidence suggests that neoantigen-based cancer vaccines possess a very promising future, yet the processes of immune recognition and activation to relay identification of a neoantigen through the histocompatibility complex (MHC) and T-cell receptor (TCR) remain unclear. Here, we describe features of neoantigens and the biological process of validating neoantigens, along with a discussion of recent progress in the scientific development and clinical applications of neoantigen-based cancer vaccines.
| S-EPMC10056833 | biostudies-literature
Project description:Personal neoantigen vaccines have been envisioned as an effective approach to induce, amplify and diversify antitumor T cell responses. To define the long-term effects of such a vaccine, we evaluated the clinical outcome and circulating immune responses of eight patients with surgically resected stage IIIB/C or IVM1a/b melanoma, at a median of almost 4 years after treatment with NeoVax, a long-peptide vaccine targeting up to 20 personal neoantigens per patient ( NCT01970358 ). All patients were alive and six were without evidence of active disease. We observed long-term persistence of neoantigen-specific T cell responses following vaccination, with ex vivo detection of neoantigen-specific T cells exhibiting a memory phenotype. We also found diversification of neoantigen-specific T cell clones over time, with emergence of multiple T cell receptor clonotypes exhibiting distinct functional avidities. Furthermore, we detected evidence of tumor infiltration by neoantigen-specific T cell clones after vaccination and epitope spreading, suggesting on-target vaccine-induced tumor cell killing. Personal neoantigen peptide vaccines thus induce T cell responses that persist over years and broaden the spectrum of tumor-specific cytotoxicity in patients with melanoma.
| S-EPMC8273876 | biostudies-literature
Project description:Alternatives to conventional cancer treatments are highly sought after for high-risk malignancies that have a poor response to established treatment modalities. With research advancing rapidly in the past decade, neoantigen-based immunotherapeutic approaches represent an effective and highly tolerable therapeutic option. Neoantigens are tumor-specific antigens that are not expressed in normal cells and possess significant immunogenic potential. Several recent studies have described the conceptual framework and methodologies to generate neoantigen-based vaccines as well as the formulation of appropriate clinical trials to advance this approach for patient care. This review aims to describe some of the key studies in the recent literature in this rapidly evolving field and summarize the current advances in neoantigen identification and selection, vaccine generation and delivery, and the optimization of neoantigen-based therapeutic strategies, including the early data from pivotal clinical studies.
| S-EPMC8877108 | biostudies-literature
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| S-EPMC10171177 | biostudies-literature
Project description:Dramatic success in cancer immunotherapy has been achieved over the last decade with the introduction of checkpoint inhibitors, leading to response rates higher than with chemotherapy in certain cancer types. These responses are often restricted to cancers that have a high mutational burden and show pre-existing T-cell infiltrates. Despite extensive efforts, therapeutic vaccines have been mostly unsuccessful in the clinic. With the introduction of next generation sequencing, the identification of individual mutations is possible, enabling the production of personalized cancer vaccines. Combining immune check point inhibitors to overcome the immunosuppressive microenvironment and personalized cancer vaccines for directing the host immune system against the chosen antigens might be a promising treatment strategy.
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Project description:Within the past decade, the field of immunotherapy has revolutionized the treatment of many cancers with the development and regulatory approval of various immune-checkpoint inhibitors and chimeric antigen receptor T cell therapies in diverse indications. Another promising approach to cancer immunotherapy involves the use of personalized vaccines designed to trigger de novo T cell responses against neoantigens, which are highly specific to tumours of individual patients, in order to amplify and broaden the endogenous repertoire of tumour-specific T cells. Results from initial clinical studies of personalized neoantigen-based vaccines, enabled by the availability of rapid and cost-effective sequencing and bioinformatics technologies, have demonstrated robust tumour-specific immunogenicity and preliminary evidence of antitumour activity in patients with melanoma and other cancers. Herein, we provide an overview of the complex process that is necessary to generate a personalized neoantigen vaccine, review the types of vaccine-induced T cells that are found within tumours and outline strategies to enhance the T cell responses. In addition, we discuss the current status of clinical studies testing personalized neoantigen vaccines in patients with cancer and considerations for future clinical investigation of this novel, individualized approach to immunotherapy.
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