Tumor-Derived Antigenic Peptides as Potential Cancer Vaccines
Abstract
:1. Introduction
2. Types of Tumor Antigens
3. Neoantigen Discovery and Selection for Peptide-Based Cancer Vaccines
4. Studies with Tumor Antigens
4.1. Melanoma Studies
4.2. Pancreatic Carcinoma Studies
4.3. Glioblastoma Studies
4.4. Lung Cancer Studies
4.5. Gastrointestinal Cancers Studies
4.6. Epithelial Cancer Studies
4.7. Multiple Tumor Studies
4.8. Breast Tumor Studies
4.9. T-Cell Recognition
5. Databases Containing Human Tumor Antigens
6. Summary and Future Perspective
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AAS | Amino acid-substitution |
AML | Acute myeloid leukemia |
APC | Antigen-presenting cell |
BRAF | B-Raf proto-oncogene |
CARs | Chimeric antigen receptors |
CD4+ T cells | CD4-expressing T cells |
CD8+ T cells | CD8-expressing T cells |
CDC | Collecting duct carcinoma |
CGA | Cancer germline antigen |
CTA | Cancer/testis antigen |
CLT | Cytotoxic T lymphocyte |
EGFR | Epidermal growth factor receptor |
EGFRvIII | Epidermal growth factor receptor variant III |
gp100 | Glycoprotein 100 |
HLA | Human leukocyte antigen |
HPV-E6/E7 | Human papillomavirus oncoproteins E6/E7 |
HTLV-1 | Human T-cell lymphotropic virus type 1 |
ITH | Intratumoral heterogeneity |
KRAS | Kirsten rat sarcoma virus |
MAGE-A3 | Melanoma antigen-A3 |
MAPK | Mitogen-activated protein kinases |
MART-1 | Melanoma antigen recognized by T cells 1 |
mDC | Mature dendritic cell |
MHC-I | MHC-Class I |
MHC-II | MHC-Class II |
MHC | Major Histocompatibility Complex |
ML | Machine learning |
NGS | Next generation sequencing |
NK cells | Natural killer cells |
NRT | Neoantigen-reactive T cell |
NSCLC | Non-small cell lung cancer |
NY-ESO-1 | New York esophageal squamous cell carcinoma 1 |
PDX | Patient-derived xenograft |
PFS | Progression-free survival |
PSA | Prostate-specific antigen |
PSL-DA | Partial least squares-Discriminant analysis |
p-MHC | peptide-MHC complex |
p53 | Tumor protein 53 |
RNA-seq | RNA-sequencing |
SCM | Scoring card method |
SNV | single nucleotide variant |
TAA | Tumor-associated antigens |
TCR | T-cell receptor |
TIL | Tumor-infiltrating lymphocyte |
TKI | Tyrosine kinase inhibitor |
TMB | Tumor mutational burden |
TSA | Tumor-specific antigens |
WES | whole-exome sequencing |
WGS | Whole genome sequencing |
WT1 | Wilms tumor 1 |
WT | Wild-type |
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Vaccine | Trade Names Examples | Target Antigen/s | Cancer Type | Use | Approved Since |
---|---|---|---|---|---|
Hepatitis B vaccine | Engerix-B®, Recombivax HB®, Heplisav-B® | Hepatitis B virus (HBV) purified surface antigen (HBsAg) | HBV-related hepatocellular carcinoma | Preventive | In use since 1981 |
Bacillus Calmette–Guérin (BCG) vaccine | Tubervac® | Non-pathogenic mycobacterium bovis | Non-muscle invasive bladder cancer (NMIBC), also used as an immune stimulant | Therapeutic | In use since 1990 |
HPV vaccines | Gardasil®, Cervarix®, Gardasil 9® | Types of L1 protein of human papilloma virus (HPV): Gardasil®—types 6, 11, 16, and 18; Cervarix®—types 16 and 18; Gardasil 9®—types 6, 11, 16, 18, 31, 33, 45, 52, and 58 | HPV-associated cervical, oropharyngeal, anal, penile, and vulvovaginal cancers | Preventive | Gardasil®—8 June 2006; Cervarix®—16 October 2009; Gardasil 9®—10 December 2014 |
Sipuleucel-T | Provenge® | Prostatic acid phosphatase | Castration-resistant prostatic cancer | Therapeutic | 29 April 2010 |
Talimogene laherparepvec | T-VEC®, Imlygic® | Does not target any antigen/s, directly destroys the cancer cells it infects | Metastatic melanoma | Therapeutic | 27 October 2015 |
Type of Tumor Antigen | Description | Tumor Specificity | Central Tolerance | Prevalence in Multiple Patients | Examples |
---|---|---|---|---|---|
Overexpressed antigens | Antigens found at increased levels in tumors compared with normal healthy cells | Variable | High | High | WT1, p53 |
Differentiation antigens | Antigens selectively expressed by the cell lineage from which malignant cells evolved | Variable | High | High | PSA, gp100 |
Cancer/testis antigens | Antigens only been found to be expressed in immune-privileged tissues (testes, fetal ovaries, trophoblast) | High | Low | High | NY-ESO-1, MAGE-A3 |
Neoantigens | Antigens that are uniquely expressed by cancer cells but not found in normal cells | Complete | None | Variable | Various mutated peptides from different proteins |
Viral antigens | Antigens derived from viral proteins that are only present in tumor cells | Complete | None | High | HPV-E6/E7, HTLV-1 |
Name | Year | Method a | Availability online (as of 1 March 2024) |
---|---|---|---|
LENS [56] | 2023 | Over two dozen separate tools to generate tumor antigen predictions | https://gitlab.com/landscape-of-effective-neoantigens-software |
OpenVax [57] | 2020 | Bioinformatics pipeline | https://github.com/openvax |
pVACtools [58] | 2020 | Various MHC-I prediction algorithms | https://github.com/griffithlab/pVACtools |
nextNEOpi [59] | 2022 | WES/WGS/RNA-Seq pipeline | https://github.com/icbi-lab/nextNEOpi |
TTAgP [60] | 2019 | RF | https://github.com/bio-coding/TTAgP |
TIminer [61] | 2017 | NGS pipeline | https://bio.tools/timiner |
iTTCA-Hybrid [62] | 2020 | RF, SVM | http://camt.pythonanywhere.com/iTTCA-Hybrid |
iTTCA-RF [63] | 2021 | RF | http://112.124.26.17:7002/ |
TAP [64] | 2021 | ML | No |
PSRTTCA [65] | 2023 | SCM | http://pmlabstack.pythonanywhere.com/PSRTTCA |
StackTTCA [66] | 2023 | Stacking ensemble-learning algorithm | No |
VaxiJen v2.0 [67] | 2007 | PSL-DA | http://www.ddg-pharmfac.net/vaxijen/VaxiJen/VaxiJen.html |
Vaccine | Description | Cancer Type | Trial Id |
---|---|---|---|
FMPV-1 | Peptide-based cancer vaccine targeting transforming growth factor beta receptor 2 (TGFBR2) | Colorectal cancer | NCT05238558 |
TENDU | Synthetic therapeutic peptide conjugate vaccine | Prostate cancer | NCT04701021 |
UV1 | Consists of three long synthetic peptides, representing 60 amino acids of the reverse transcriptase subunit of human telomerase (hTERT) | Malignant pleural mesothelioma | NCT04574583 |
RO7198457 | mRNA-based individualized, therapeutic cancer vaccine targeting an unspecified number of tumor-associated antigens (TAAs) | Pancreatic cancer | NCT04161755 |
EO2401 | Peptide therapeutic vaccine based on the homologies between tumor associated antigens and microbiome-derived peptides | Glioblastoma | NCT04116658 |
RV001V | Vaccine composed of an immunogenic peptide derived from the Ras homolog family member C (RhoC; Rho-related GTP-binding protein RhoC) | Prostate cancer | NCT04114825 |
Galinpepimut-S (GPS) | Peptide cancer vaccine comprised of four peptide chains derived from the Wilms’ tumor gene 1 (WT1) protein | Mesothelioma | NCT04040231 |
AE37 | HER2-directed vaccine based on the AE36 hybrid peptide (aa776-790) | Triple-negative breast cancer | NCT04024800 |
Neoantigen peptide vaccine | Neoantigen peptide vaccines will incorporate prioritized neoantigens and personalized mesothelin epitopes | Pancreatic cancer | NCT03956056 |
GRT-C903 and GRT-R904 | Neoantigen-based therapeutic cancer vaccines based on tumor-specific shared neoantigens, which are immunogenic and unique across a subset of patients | Advanced solid tumors | NCT03953235 |
UCPVax | Therapeutic cancer vaccine composed of two separate peptides derived from telomerase (hTERT, human telomerase reverse transcriptase) | HPV-positive cancers | NCT03946358 |
iNeo-Vac-P01 | Personalized neoantigen peptide cancer vaccine (5~20 peptides with the length ranging from 15 to 35 amino acids) | Advanced malignant solid tumors | NCT03662815 |
PVX-410 | Multipeptide therapeutic cancer | Breast cancers | NCT03362060 |
DPX-Survivac | Vaccine composed of survivin-based synthetic peptide antigens and an adjuvant | Lymphomas | NCT03349450 |
MUC1 peptide-Poly-ICLC | Vaccine composed of 100-amino acid synthetic MUC1 peptide | Lung carcinoma | NCT03300817 |
H3.3.K27M | Synthetic peptide vaccine specific for the H3.3.K27M epitope | Gliomas | NCT02960230 |
IMA950 | Multipeptide vaccine containing 11 glioma-associated antigens among which 9 are HLA-A*0201-restricted peptides, and 2 are HLA class II-binding peptides | Grade II low-grade glioma (LGG) | NCT02924038 |
IMU-131 | B-cell peptide vaccine composed of a fusion of 3 epitopes from the extracellular domain of HER2/neu conjugated to CRM197 with the adjuvant Montanide | HER2-positive advanced gastric cancer | NCT02795988 |
Nelipepimut-S (E75) | Nine amino acid sequence from the extracellular domain of the HER2 receptor (residues 369–377 of HER2neu: KIFGSLAFL) | Breast ductal carcinoma | NCT02636582 |
SurVaxM (SVN53-67/M57-KLH) | Synthetic long peptide mimic peptide that spans amino acids 53 through 67 of the human survivin protein sequence | Glioblastoma | NCT02455557 |
CMVpp65-A*0201 | Antigenic peptide NLVPMVATV | Hematologic malignancies | NCT02396134 |
HLA-A2-restricted synthetic glioma antigen peptides vaccine | Vaccine consisting of HLA-A2-restricted peptides derived from glioma-associated antigens (GAAs) | Pediatric gliomas | NCT01130077 |
Bivalent vaccine | Vaccine consisting of two cell-surface antigens (GD2L and GD3L) | Neuroblastoma | NCT00911560 |
Subject | Target | Number of Patients | Outcome | Reference |
---|---|---|---|---|
Epitope vaccination | Melanoma | 37 | Identification of T-cell immunogens in metastatic melanoma. Endogenous responses directed at other melanoma antigens. | Khong et al. [69] |
Melanoma antigens (MAGE) vaccination | Melanoma | 1 | Identification of T-cell immunogens in metastatic melanoma. Antigen spreading. | Corbiere et al. [70] |
Dendritic cells vaccination | Melanoma | 3 | Identification of T-cell immunogens in melanoma. Discovery of previously undetected HLA class I-restricted neoantigens. | Carreno et al. [71] |
Identification of T-cell immunogens | Melanoma | 8 | A methodology to facilitate the isolation of neoantigen-specific T cells derived from tumor and peripheral lymphocytes. Isolation of neoantigen-specific T cells. | Cohen et al. [72] |
Mature dendritic cell (mDC) vaccination | Melanoma | 4 | Identification of T-cell immunogens in melanoma. CD8+ T-cell responses, encompassing multiple neoantigen-specific TCR clonotypes. | Linette et al. [73] |
Personalized neoantigen vaccines | Melanoma | 8 | Identification of T-cell immunogens in melanoma. A long-term persistence of neoantigen-specific T-cell responses following vaccination. | Hu et al. [74] |
Personalized RNA-based vaccination | Melanoma | 13 | Identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a personalized vaccine. | Sahin et al. [75] |
KRAS-mutated peptide vaccination | Pancreatic adenocarcinoma | 24 | Limited immunogenicity. | Abou-Alfa et al. [76] |
KRAS-mutated peptide vaccination | Pancreatic adenocarcinoma | 1 | Identification of immunogenic mutations in KRAS peptides and specific KRAS-targeting TCRs. | Dillard et al. [77] |
Personalized multipeptide vaccination | Pancreatic ductal carcinoma | 1 | Identification of T-cell immunogens. Vaccine induced a multifaceted and persistent immune response. | Sonntag et al. [78] |
Neoantigen-derived personalized cancer vaccination | Advanced pancreatic cancer | 7 | Identification of T-cell immunogens. An extended mean overall survival accompanied by an increase in antigen-specific TCR clones post-vaccination. | Chen et al. [79] |
Multi-epitope, personalized neoantigen vaccination | Glioblastoma | 10 | Identification of T-cell immunogens. Tumor recurrence and the progression of the disease after vaccination. | Keskin et al. [80] |
Autologous tumor lysate-dendritic cell vaccine followed by a neoantigen-based synthetic long peptide vaccine | Glioblastoma | 1 | Identification of T-cell immunogens. Presence of discernible CD8+ and CD4+ T-cell responses specifically directed towards neoantigens induced by the peptide vaccine. | Johanns et al. [81] |
Multi-epitope peptide vaccination | Lung squamous cell carcinoma | 1 | Identification of T-cell immunogens. A substantial reduction in tumor size and positive clinical outcomes. | Li et al. [82] |
Personalized neoantigen peptide vaccination | Non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations | 24 | Identification of T-cell immunogens. Vaccine-induced T-cell responses directed towards EGFR NeoAg peptides. | Li et al. [83] |
Identification of T-cell immunogens | Gastrointestinal cancer | 10 | Identification of T-cell immunogens. Presence of tumor-mutation-specific T cells. | Tran et al. [84] |
Identification of T-cell immunogens | Metastatic epithelial cancer | 6 | Identification of T-cell immunogens in epithelial cancer. Detected existence of specific T cells in the peripheral blood. | Cafri et al. [85] |
Personalized neoantigen-based vaccination and T-cell immunotherapy | Duct carcinoma | 1 | Identification of T-cell immunogens in advanced collecting duct carcinoma. A reduction in mutant allele frequency corresponding to 92% of the neoantigens. | Zeng et al. [86] |
Personalized neoantigen-based vaccine, in combination with Nivolumab | Advanced melanoma, non-small cell lung cancer, bladder cancer | 82 | Identification of T-cell immunogens in various cancers. Antigen spreading. | Ott et al. [87] |
Personalized neoantigen-based vaccine | Breast tumor | 1 | Identification of T-cell immunogens in phyllodes tumor. Pathological complete response in the lung metastasis. | Sha et al. [88] |
Neoantigen vaccination in preclinical models | Murine breast tumor | Mice | Anti-tumor immune responses in preclinical models and neoantigen-specific responses in clinical translation | Li et al. [89] |
Effects of peptide anchor modification on T-cell recognition | T-cell leukemia | - | Improved T-cell recognition | Smith et al. [90] |
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Sotirov, S.; Dimitrov, I. Tumor-Derived Antigenic Peptides as Potential Cancer Vaccines. Int. J. Mol. Sci. 2024, 25, 4934. https://doi.org/10.3390/ijms25094934
Sotirov S, Dimitrov I. Tumor-Derived Antigenic Peptides as Potential Cancer Vaccines. International Journal of Molecular Sciences. 2024; 25(9):4934. https://doi.org/10.3390/ijms25094934
Chicago/Turabian StyleSotirov, Stanislav, and Ivan Dimitrov. 2024. "Tumor-Derived Antigenic Peptides as Potential Cancer Vaccines" International Journal of Molecular Sciences 25, no. 9: 4934. https://doi.org/10.3390/ijms25094934