Neoantigen-based Immunotherapy Research Articles

Driver mutation landscape of acute myeloid leukemia provides insights for neoantigen-based immunotherapy.

Acute myeloid leukemia (AML) has lagged in benefiting from immunotherapies, primarily due to the scarcity of actionable AML-specific antigens. Driver mutations represent promising immunogenic targets, but a comprehensive characterization of the AML neoantigen landscape and their impact on patient outcomes and the AML immune microenvironment remain unclear. Herein, we conducted matched DNA and RNA sequencing on 304 AML patients and extensively integrated data from additional ∼2,500 AML cases, identifying 49 driver genes, notably characterized by a significant proportion of insertions and deletions (indels). Neoantigen analysis showed that indels triggered a higher abundance of neoantigens both in quantity and quality compared to single nucleotide variants (SNVs) and gene fusions. By integrating peptide features pertinent to neoantigen presentation and T cell recognition, we developed two robust models of epitope immunogenicity that significantly enriched immunogenic neoepitopes. We validated 30 neoantigens through in vitro direct binding assays of predicted peptides to MHC proteins and confirmed the immunogenicity of 20 neoantigens using interferon-γ ELISpot and tetramer assays. Moreover, we demonstrated that patients with higher neoantigen loads, derived from driver mutations, exhibited poor clinical outcomes and an IFN-driven adaptive immune response, which was associated with immune suppression and tumor evasion. Through deconvolution of large-scale bulk transcriptomes, integration of single-cell RNA sequencing and multiparametric flow cytometry, we confirmed a strong association between neoantigen load and CD8+ T cell exhaustion. This study provides a comprehensive landscape of AML neoantigens derived from driver mutations, offering putative immunogenic targets and emphasizing the need for strategies to revitalize the immunosuppressive milieu.

ARID1A-Deficient Tumors Acquire Immunogenic Neoantigens during the Development of Resistance to Targeted Therapy.

Neoantigen-based immunotherapy is an attractive potential treatment for previously intractable tumors. To effectively broaden the application of this approach, stringent biomarkers are crucial to identify responsive patients. ARID1A, a frequently mutated subunit of SWI/SNF chromatin remodeling complex, has been reported to determine tumor immunogenicity in some cohorts; however, mutations and deletions of ARID1A are not always linked to clinical responses to immunotherapy. In this study, we investigated immunotherapeutic responses based on ARID1A status in targeted therapy-resistant cancers. Mouse and human BRAFV600E melanomas with or without ARID1A expression were transformed into resistant to vemurafenib, an FDA-approved specific BRAFV600E inhibitor. Anti-PD-1 antibody treatment enhanced antitumor immune responses in vemurafenib-resistant ARID1A-deficient tumors but not in ARID1A-intact tumors or vemurafenib-sensitive ARID1A-deficient tumors. Neoantigens derived from accumulated somatic mutations during vemurafenib resistance were highly expressed in ARID1A-deficient tumors and promoted tumor immunogenicity. Furthermore, the newly generated neoantigens could be utilized as immunotherapeutic targets by vaccines. Finally, targeted therapy resistance-specific neoantigen in experimental human melanoma cells lacking ARID1A were validated to elicit T-cell receptor responses. Collectively, the classification of ARID1A-mutated tumors based on vemurafenib resistance as an additional indicator of immunotherapy response will enable a more accurate prediction to guide cancer treatment. Furthermore, the neoantigens that emerge with therapy resistance can be promising therapeutic targets for refractory tumors. Significance: Chemotherapy resistance promotes the acquisition of immunogenic neoantigens in ARID1A-deficient tumors that confer sensitivity to immune checkpoint blockade and can be utilized for developing antitumor vaccines, providing strategies to improve immunotherapy efficacy.

Characteristics of tumor-rejecting neoantigens identified in a physiologically relevant cutaneous squamous cell carcinoma model

Abstract Challenges in identifying tumor-rejecting neoantigens limit the use of neoantigen-based immunotherapies to treat high mutational burden tumors, such as cutaneous squamous cell carcinoma (cSCC). Most mutations in human cSCC are unique to an individual tumor. Only a small portion of human tumors share neoantigens predicted to bind MHC, supporting the need for personalized strategies. We generated transplantable cell lines, from solar UV-induced cSCC tumors, which recapitulate the UV mutational signature and driver mutations found in human disease. Depletion of CD8 and CD4 T cells revealed a dominant role for CD8 T cells and a supporting role for CD4 T cells in constraining cSCC. Vaccination with irradiated cSCC cells completely protects from tumor challenge and is dependent on CD8 T cells. Neoantigens were prioritized based on predicted binding affinity, MHC presentation and expression. IFN-γ-secreting CD8 T cells recognizing two neoantigens were present in cSCC tumors and tumor-draining lymph nodes. Prophylactic vaccination with these neoantigens constrained cSCC growth. Structural modeling of tumor-rejecting neoantigens in cSCC and other cancer models identified an increased solvent accessible surface area of the mutated residue in tumor-rejecting neoantigens compared to non-immunogenic neoantigens, which is anticipated to improve TCR recognition. This work provides a conceptual basis for consideration of TCR recognition in the prioritization of tumor-rejecting neoantigens.

Tumor neoantigens and tumor immunotherapies.

As a high-risk group of patients with cancer, the elderly exhibit limited efficacy with traditional treatments. Immunotherapy emerges as a promising adjunctive therapeutic approach that holds potential in addressing the needs of geriatric patients with cancer. Neoantigens, a unique class of tumor-specific antigens generated by non-synonymous mutations, are garnering increasing attention as targets for immunotherapy in clinical applications. Newly developed technologies, such as second-generation gene sequencing and mass spectrometry, have provided powerful technical support for the identification and prediction of neoantigens. At present, neoantigen-based immunotherapy has been extensively applied in clinical trials and has demonstrated both safety and efficacy, marking the beginning of a new era for cancer immunotherapy. This article reviews the conception, classification, inducers, and screening process of tumor neoantigens, as well as the application prospects and combination therapy strategies of neoantigen-based cancer immunotherapy.

Circular RNA as a source of neoantigens for cancer vaccines

BackgroundThe effectiveness of somatic neoantigen-based immunotherapy is often hindered by the limited number of mutations in tumors with low to moderate mutation burden. Focusing on microsatellite-stable colorectal cancer (CRC), this...

NeoTCR: an immunoinformatic database of experimentally-supported functional neoantigen-specific TCR sequences.

Neoantigen-based immunotherapy has demonstrated long-lasting antitumor activity. The recognition of neoantigens by T cell receptors (TCRs) is considered a trigger for antitumor responses. Due to the overwhelming number of TCR repertoires in the human genome, pinpointing neoantigen-specific TCRs is a formidable challenge. Recent studies have identified a number of functional neoantigen-specific TCRs, but the corresponding information is scattered across published literature and is difficult to retrieve. To improve access to these data, we developed an immunoinformatic database (NeoTCR) containing a unified description of publicly available neoantigen-specific TCR sequences, as well as relevant information on targeted neoantigens, from experimentally supported studies across 18 cancer subtypes. A user-friendly web interface allows interactive browsing and running of complex database queries. To facilitate rapid identification of neoantigen-specific TCRs from raw sequencing data, NeoTCR offers a one-stop analysis for annotation and visualization of TCR clonotypes, discovery of existing neoantigen-specific TCRs, and exclusion of bystander viral-associated TCRs. NeoTCR represents a unique tool to expedite future studies of neoantigen-specific TCRs and the development of neoantigen-based immunotherapy. NeoTCR is available at http://neotcrdb.bioaimed.com/ and https://github.com/lyotvincent/NeoTCR.

Advancing nanotechnology for neoantigen-based cancer theranostics.

Neoantigens play a pivotal role in the field of tumour therapy, encompassing the stimulation of anti-tumour immune response and the enhancement of tumour targeting capability. Nonetheless, numerous factors directly influence the effectiveness of neoantigens in bolstering anti-tumour immune responses, including neoantigen quantity and specificity, uptake rates by antigen-presenting cells (APCs), residence duration within the tumour microenvironment (TME), and their ability to facilitate the maturation of APCs for immune response activation. Nanotechnology assumes a significant role in several aspects, including facilitating neoantigen release, promoting neoantigen delivery to antigen-presenting cells, augmenting neoantigen uptake by dendritic cells, shielding neoantigens from protease degradation, and optimizing interactions between neoantigens and the immune system. Consequently, the development of nanotechnology synergistically enhances the efficacy of neoantigens in cancer theranostics. In this review, we provide an overview of neoantigen sources, the mechanisms of neoantigen-induced immune responses, and the evolution of precision neoantigen-based nanomedicine. This encompasses various therapeutic modalities, such as neoantigen-based immunotherapy, phototherapy, radiotherapy, chemotherapy, chemodynamic therapy, and other strategies tailored to augment precision in cancer therapeutics. We also discuss the current challenges and prospects in the application of neoantigen-based precision nanomedicine, aiming to expedite its clinical translation.

Neoantigens: The Novel Precision Cancer Immunotherapy

The past few decades have witnessed the remarkable progress of cancer immunotherapy. Neoantigens, also known as tumor-specific antigens, are novel antigens originating from tumor-specific alterations such as genomic mutations, dysregulated RNA splicing, and post-translational modifications. Neoantigens, recognized as non-self entities, trigger immune responses that evade central and peripheral tolerance mechanisms. With the notable strides in cancer genomics facilitated by next-generation sequencing technologies, neoantigens have emerged as a promising avenue for tumor-specific immunotherapy grounded in genomic profiling-based precision medicine. Furthermore, a growing number of preclinical and clinical investigations are harnessing the potential synergies between neoantigens and other immunotherapies such as adoptive cell therapy and immune checkpoint inhibitors. In this review, we will provide a comprehensive perspective encompassing the trajectory of neoantigens, neoantigen design strategies, and the diverse array of clinical applications inherent in immunotherapy strategies centered around neoantigens. Moreover, we delve into the inherent prospects and challenges that accompany the clinical adoption of neoantigen-based immunotherapies while also putting forth potential solutions to address these challenges.

Machine learning methods and harmonized datasets improve immunogenic neoantigen prediction

The accurate selection of neoantigens that bind to class I human leukocyte antigen (HLA) and are recognized by autologous Tcells is a crucial step in many cancer immunotherapy pipelines. We reprocessed whole-exome sequencing and RNA sequencing (RNA-seq) data from 120 cancer patients from two external large-scale neoantigen immunogenicity screening assays combined with an in-house dataset of 11 patients and identified 46,017 somatic single-nucleotide variant mutations and 1,781,445 neo-peptides, of which 212 mutations and 178 neo-peptides were immunogenic. Beyond features commonly used for neoantigen prioritization, factors such as the location of neo-peptides within protein HLA presentation hotspots, binding promiscuity, and the role of the mutated gene in oncogenicity were predictive for immunogenicity. The classifiers accurately predicted neoantigen immunogenicity across datasets and improved their ranking by up to 30%. Besides insights into machine learning methods for neoantigen ranking, we have provided homogenized datasets valuable for developing and benchmarking companion algorithms for neoantigen-based immunotherapies.

Improvement in neoantigen prediction via integration of RNA sequencing data for variant calling.

Neoantigen-based immunotherapy has emerged as a promising strategy for improving the life expectancy of cancer patients. This therapeutic approach heavily relies on accurate identification of cancer mutations using DNA sequencing (DNAseq) data. However, current workflows tend to provide a large number of neoantigen candidates, of which only a limited number elicit efficient and immunogenic T-cell responses suitable for downstream clinical evaluation. To overcome this limitation and increase the number of high-quality immunogenic neoantigens, we propose integrating RNA sequencing (RNAseq) data into the mutation identification step in the neoantigen prediction workflow. In this study, we characterize the mutation profiles identified from DNAseq and/or RNAseq data in tumor tissues of 25 patients with colorectal cancer (CRC). Immunogenicity was then validated by ELISpot assay using long synthesis peptides (sLP). We detected only 22.4% of variants shared between the two methods. In contrast, RNAseq-derived variants displayed unique features of affinity and immunogenicity. We further established that neoantigen candidates identified by RNAseq data significantly increased the number of highly immunogenic neoantigens (confirmed by ELISpot) that would otherwise be overlooked if relying solely on DNAseq data. This integrative approach holds great potential for improving the selection of neoantigens for personalized cancer immunotherapy, ultimately leading to enhanced treatment outcomes and improved survival rates for cancer patients.

Personalized neoantigen viro-immunotherapy platform for triple-negative breast cancer

BackgroundTriple-negative breast cancer (TNBC) corresponds to approximately 20% of all breast tumors, with a high propensity for metastasis and a poor prognosis. Because TNBC displays a high mutational load compared...

Chemically modified neoantigen-based immunotherapy for targeting KRASG12C-driven tumors

The clinical efficacy and durability of KRASG12C-targeted therapies are limited by the development of resistance mechanisms. Here, we provide a review of recent KRASG12C-targeted therapy and immunotherapy-unifying strategies that utilize covalently modified peptide/MHC class I complexes as tumor-specific neoantigens to tag drug-resistant cancer cells for destruction with hapten-based immunotherapeutics.

Cell membrane-camouflaged liposomes and neopeptide-loaded liposomes with TLR agonist R848 provides a prime and boost strategy for efficient personalized cancer vaccine therapy

Recent advances in bioinformatics and nanotechnology offer great opportunities for personalized cancer vaccine development. However, the timely identification of neoantigens and unsatisfactory efficacy of therapeutic cancer vaccines remain two obstacles for clinical transformation. We propose a “prime and boost” strategy to facilitate neoantigen-based immunotherapy. To prime the immune system, we first constructed personalized liposomes with cancer cell membranes and adjuvant R848 to provide immunostimulatory efficacy and time for identifying tumor antigens. Liposomes loaded with personalized neopeptides and adjuvants were used to boost the immune response. In vitro experiments verified potent immune responses, including macrophage polarization, dendritic cell maturation, and T lymphocyte activation. In vivo B16F10 and TC-1 cancer model were used to investigate efficient tumor growth suppression. Liposomal vaccines with neopeptides could stimulate human dendritic cells and T lymphocytes in vitro. These results demonstrate that the “prime and boost” strategy provides simple, quick, and efficient personalized vaccines for cancer therapy.

Deciphering colorectal cancer immune microenvironment transcriptional landscape on single cell resolution - A role for immunotherapy.

Single cell RNA sequencing (scRNA-seq) is a novel high-throughput technique that enables the investigation of a single cell’s entire transcriptome. It elucidates intricate cellular networks and generates indices that will eventually enable the development of more targeted and personalized medications. The importance of scRNA-seq has been highlighted in complex biological systems such as cancer and the immune system, which exhibit significant cellular heterogeneity. Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related death globally. Chemotherapy continues to be used to treat these patients. However, 5-FU has been utilized in chemotherapy regimens with oxaliplatin and irinotecan since the 1960s and is still used today. Additionally, chemotherapy-resistant metastatic CRCs with poor prognoses have been treated with immunotherapy employing monoclonal antibodies, immune checkpoint inhibitors, adoptive cell therapy and cancer vaccines. Personalized immunotherapy employing tumor-specific neoantigens allows for treating each patient as a distinct group. Sequencing and multi-omics approaches have helped us identify patients more precisely in the last decade. The introduction of modern methods and neoantigen-based immunotherapy may usher in a new era in treating CRC. The unmet goal is to better understand the cellular and molecular mechanisms that contribute to CRC pathogenesis and resistance to treatment, identify novel therapeutic targets, and make more stratified and informed treatment decisions using single cell approaches. This review summarizes current scRNA-seq utilization in CRC research, examining its potential utility in the development of precision immunotherapy for CRC.

Identification of shared neoantigens in esophageal carcinoma by the combination of comprehensive analysis of genomic data and in silico neoantigen prediction

Neoantigens are attractive targets for cancer immunotherapy. The identification of neoantigens shared by different patients could promote the broad application of neoantigen-based immunotherapy. This study aimed to investigate shared neoantigens in esophageal carcinoma. By combining a comprehensive analysis of mutation data of 722 patients with esophageal carcinoma (EC) and in silico neoantigen prediction, we obtained 216 recurrent neoantigen candidates predicted to bind to high-frequency class I human leukocyte antigen (HLA) alleles. We further performed immunogenicity validation tests on five high-frequency HLA-A*0201 binding neoantigens derived from TP53 mutations. The results demonstrated that the peptides p53 H193R193_203, R248Q245_254, and R273H264_274 could efficiently prime peptide-specific CD8+ T cells to secrete IFN-γ and lyse mutant peptide-pulsed T2 cells. In conclusion, we obtained a group of shared neoantigen candidates in esophageal carcinoma and validated the immunogenicity of three novel TP53 neoantigens. These peptides might be potential targets for immunotherapy.

A Comprehensive Survey of Genomic Mutations in Breast Cancer Reveals Recurrent Neoantigens as Potential Therapeutic Targets.

Neoantigens are mutated antigens specifically generated by cancer cells but absent in normal cells. With high specificity and immunogenicity, neoantigens are considered as an ideal target for immunotherapy. This study was aimed to investigate the signature of neoantigens in breast cancer. Somatic mutations, including SNVs and indels, were obtained from cBioPortal of 5991 breast cancer patients. 738 non-silent somatic variants present in at least 3 patients for neoantigen prediction were selected. PIK3CA (38%), the highly mutated gene in breast cancer, could produce the highest number of neoantigens per gene. Some pan-cancer hotspot mutations, such as PIK3CA E545K (6.93%), could be recognized by at least one HLA molecule. Since there are more SNVs than indels in breast cancer, SNVs are the major source of neoantigens. Patients with hormone receptor-positive or HER2 negative are more competent to produce neoantigens. Age, but not the clinical stage, is a significant contributory factor of neoantigen production. We believe a detailed description of breast cancer neoantigen signatures could contribute to neoantigen-based immunotherapy development.

Identification of Neoantigens in Two Murine Gastric Cancer Cell Lines Leading to the Neoantigen-Based Immunotherapy.

Simple SummaryDespite the success of immune checkpoint inhibitors (ICI) for treating a variety of solid cancers, most gastric cancer patients are resistant to ICI monotherapies. Combinations of ICI with other therapies may be able to overcome this resistance. In order to develop combination immunotherapies, immunologically well-characterized preclinical gastric cancer models are required. To this end, in the present study, we characterized two murine gastric cancer cell lines, namely, YTN2 which spontaneously regresses, and YTN16 which grows progressively. Although anti-CTLA-4 monotherapy eradicated most YTN16 tumors, these were resistant to either anti-PD-1 or anti-PD-L1 treatment. Furthermore, we identified neoantigens in YTN2 and YTN16 tumors and conducted neoantigen-based immunotherapy for these tumors. In addition, the information on neoantigens facilitates the evaluation of tumor-specific immune responses induced by the combination therapies. These immunologically well-characterized gastric cancer models will contribute to the development of novel combination immunotherapies.To develop combination immunotherapies for gastric cancers, immunologically well-characterized preclinical models are crucial. Here, we leveraged two transplantable murine gastric cancer cell lines, YTN2 and YTN16, derived from the same parental line but differing in their susceptibility to immune rejection. We established their differential sensitivity to immune checkpoint inhibitors (ICI) and identified neoantigens. Although anti-CTLA-4 mAbs eradicated YTN16 tumors in 4 of 5 mice, anti-PD-1 and anti-PD-L1 mAbs failed to eradicate YTN16 tumors. Using whole-exome and RNA sequencing, we identified two and three neoantigens in YTN2 and YTN16, respectively. MHC class I ligandome analysis detected the expression of only one of these neoantigens, mutated Cdt1, but the exact length of MHC binding peptide was determined. Dendritic cell vaccine loaded with neoepitope peptides and adoptive transfer of neoantigen-specific CD8+ T cells successfully inhibited the YTN16 tumor growth. Targeting mutated Cdt1 had better efficacy for controlling the tumor. Therefore, mutated Cdt1 was the dominant neoantigen in these tumor cells. More mCdt1 peptides were bound to MHC class I and presented on YTN2 surface than YTN16. This might be one of the reasons why YTN2 was rejected while YTN16 grew in immune-competent mice.

Personalized Immunotherapy in Colorectal Cancers: Where Do We Stand?

Colorectal cancer (CRC) is the second leading cause of cancer death in the world. Immunotherapy using monoclonal antibodies, immune-checkpoint inhibitors, adoptive cell therapy, and cancer vaccines has raised great hopes for treating poor prognosis metastatic CRCs that are resistant to the conventional therapies. However, high inter-tumor and intra-tumor heterogeneity hinder the success of immunotherapy in CRC. Patients with a similar tumor phenotype respond differently to the same immunotherapy regimen. Mutation-based classification, molecular subtyping, and immunoscoring of CRCs facilitated the multi-aspect grouping of CRC patients and improved immunotherapy. Personalized immunotherapy using tumor-specific neoantigens provides the opportunity to consider each patient as an independent group deserving of individualized immunotherapy. In the recent decade, the development of sequencing and multi-omics techniques has helped us classify patients more precisely. The expansion of such advanced techniques along with the neoantigen-based immunotherapy could herald a new era in treating heterogeneous tumors such as CRC. In this review article, we provided the latest findings in immunotherapy of CRC. We elaborated on the heterogeneity of CRC patients as a bottleneck of CRC immunotherapy and reviewed the latest advances in personalized immunotherapy to overcome CRC heterogeneity.

Abstract 1571: Neoantigen vaccine plus CD38 blockade suppress the proliferation of murine cold lung cancer LLC1

Abstract Immune checkpoint inhibitors are now the mainstay for the treatment of lung cancer. However, so-called cold tumors are known to be resistant to checkpoint inhibitors. Neoantigens associated with genetic mutations of the tumor have the potential to stimulate a potent and highly specific immune response. To develop effective immunotherapy for cold lung cancer, we examined whether neoantigen-based immunotherapy can develop immune responses and display anti-tumor effects on the cold lung cancer model, Lewis lung carcinoma cells (LLC1) resistant to anti-CTLA-4 or anti-PD-1 therapy. LLC1 cells were subjected to whole-exome and RNA sequencing. Mutation-associated neoantigens were predicted and prioritized by their affinity to MHC class I molecules and their expression. Using netMHCpan, sixty mutated peptides with IC50 <200 nM and 68 mutated peptides with IC50>200 nM, but the wild to corresponding mutated peptide ratio of binding affinity>10 were selected as candidate neoantigens. C57BL/6 mice were immunized with dendritic cells pulsed with these neoantigen short peptides (8-10mer). Twenty-five out of 128 short mutated peptides induced peptide-specific CD8+ T cell response to some extent. Next, 25 long peptides (21mer), which incorporated corresponding immunogenic short peptide sequences, were synthesized and used to immunize mice. DC vaccines pulsed with neoantigen in long peptide format (LP) induced both CD4+ and CD8+ T cell response ex vivo. Of them, DC pulsed with LP82 partly delayed the LLC1 growth in vivo. By RNA-Seq, CD38 was highly expressed in LLC1. Thereby, an anti-CD38 antibody was administered in LLC1-bearing mice immunized with DC pulsed with LP82. The tumor growth was suppressed in the combination treatment. Although CD38 plays an important role in converting nicotinamide adenine dinucleotide (NAD+) to adenosine, adenosine receptor antagonist could not inhibit the tumor growth in mice immunized with LP82. Alternatively, NAD+ accumulation due to CD38 blockade decreased regulatory T cells in the tumor immune microenvironment, consistent with the decreased Foxp3+ transcription and increased IFNg and IL2 production of CD4+ T cells sorted from tumor immune microenvironment. Our study suggested that the prioritization of neoantigens that can induce anti-tumor response is critical for developing neoantigen-targeting immunotherapy. Combining an effective neoantigen vaccine and precise immune modulator could enhance anti-tumor activities even in cold lung tumors. Citation Format: Changbo Sun, Koji Nagaoka, Akihiro Hosoi, Yukari Kobayashi, Jun Nakajima, Kazuhiro Kakimi. Neoantigen vaccine plus CD38 blockade suppress the proliferation of murine cold lung cancer LLC1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1571.

Personalized neoantigen-based cancer immunotherapy. A literature review

Introduction: The progress made in cancer immunotherapy and the clinical response of patients who have undergone this type of therapy have made it the fourth pillar of cancer treatment. Objective: To briefly describe the biological rationale of personalized neoantigen-based cancer immunotherapy, the current perspectives regarding its development, and some of the clinical outcomes achieved with this therapy. Materials and methods: A literature search was performed in PubMed, Scopus and EBSCO using the following search strategy: type of articles: original experimental studies, clinical trials, and narrative and systematic reviews addressing methods to identify mutations found in tumors and cancer immunotherapy strategies based on neoantigen-based vaccines; study population: humans and animal models; publication period: January 1989 - December 2019; language: English and Spanish; search terms: “Immunotherapy”, “Neoplasms”, “Mutation” and “Cancer Vaccines”. Results: The initial search started with 1 344 records. Once duplicates were removed (n=176), 780 studies were excluded after reading their abstract and title. The full text of 338 articles was read to confirm which met the inclusion criteria, finally including 73 studies for full analysis. All articles retrieved were published in English and were mainly conducted in the USA (43.83%) and Germany (23.65%). In the case of original studies (n=43), 20 were performed in humans only, 9 in animals only, 2 in both models, and 12 used in silico methodology. Conclusion: Personalized cancer immunotherapy with tumor neoantigen-based vaccines is strongly emerging as a new alternative to treat cancer. However, to achieve its appropriate implementation, it is necessary to use it in combination with conventional treatments, produce more knowledge that helps clarify cancer immunobiology, and reduce the costs associated with its production.