Cancer vaccines as promising immuno-therapeutics: platforms and current progress

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: March 18, 2022

Abstract Research on tumor immunotherapy has made tremendous progress in the past decades, with numerous studies entering clinical evaluation. The cancer vaccine is considered a promising therapeutic strategy of solid tumors. Cancer stimulates anti-tumor immunity antigens, which could be delivered form whole cells, peptides, nucleic acids, etc . Ideal vaccines overcome immune suppression tumors and induce both humoral cellular immunity. In this review, we introduced working mechanism summarized four platforms for development. We also highlighted research vaccines, especially focusing their application efficacy, might hopefully facilitate future design vaccine.

Language: Английский

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Metastatic colorectal cancer: mechanisms and emerging therapeutics

Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 44(4), P. 222 - 236

Published: Feb. 23, 2023

Language: Английский

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Understanding the tumor microenvironment for effective immunotherapy

Medicinal Research Reviews, Journal Year: 2020, Volume and Issue: 41(3), P. 1474 - 1498

Published: Dec. 4, 2020

Abstract Advances in immunotherapy have led to durable and long‐term benefits a subset of patients across number solid tumor types. Understanding the subsets that respond immune checkpoint inhibitors at cellular level, context their microenvironment (TME) is becoming increasingly important. The TME composed heterogeneous milieu cells. landscape can inhibit or promote initiation progression; thus, deeper understanding immunity necessary develop immunotherapeutic strategies. Recent developments focused on characterizing contexture (type, density, function) discover mechanisms biomarkers may predict treatment outcomes. This has, part, been powered by advancements spatial characterization technologies. In this review article, we address role specific cells within various stages progression how determinants affecting growth are used therapeutically.

Language: Английский

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Differentiation and Regulation of TH Cells: A Balancing Act for Cancer Immunotherapy

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: May 3, 2021

Current success of immunotherapy in cancer has drawn attention to the subsets T H cells tumor which are critical for activation anti-tumor response either directly by themselves or stimulating cytotoxic cell activity. However, presence immunosuppressive pro-tumorigenic milieu further contributes complexity regulation cell-mediated immune response. In this review, we present an overview multifaceted positive and negative effects cells, with emphasis on different subtypes various how a delicate balance contradictory signals can influence overall immunotherapy. We focus regulatory network that encompasses dendritic cell-induced CD4 + 1 subsequent priming CD8 along intersecting anti-inflammatory 2 discuss other infiltrating such as immunostimulatory 9 fh reg duality 17 function contribute tip anti- vs responses tumor. highlight developing knowledge against neoantigens/oncodrivers, impact current strategies immunity, opposing action be explored amplify patients. Understanding nuances molecular framework undergirding balancing act between is rational designing immunotherapies bypass therapeutic escape maximize potential

Language: Английский

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Personalized Cancer Vaccines: Clinical Landscape, Challenges, and Opportunities

Molecular Therapy, Journal Year: 2020, Volume and Issue: 29(2), P. 555 - 570

Published: Sept. 30, 2020

Tremendous innovation is underway among a rapidly expanding repertoire of promising personalized immune-based treatments. Therapeutic cancer vaccines (TCVs) are attractive systemic immunotherapies that activate and expand antigen-specific CD8+ CD4+ T cells to enhance anti-tumor immunity. Our review highlights key issues impacting TCVs in clinical practice reports on progress development. We the mechanism action, immune-monitoring, dosing strategies, combinations, obstacles, regulation vaccines. Most trials ongoing represent diverse platforms with predominantly early investigations mRNA, DNA, or peptide-based targeting strategies against neoantigens solid tumors, many combination immunotherapies. Multiple delivery systems, routes administration, used. Intravenous intramuscular administration common, including by lipid nanoparticles. Absorption biodistribution impact antigen uptake, expression, presentation, affecting strength, speed, duration immune response. The emerging illustrate complexity developing this class innovative Methodical testing multiple potential factors influencing responses, as well refined quantitative methodologies facilitate optimal could help resolve uncertainty therapeutic approaches. To increase likelihood success bringing these medicines patients, several unique development challenges must be overcome. have been heavily investigated for past 50 years investigational aim elicit new, strengthen existing, cytotoxic cell lymphocyte (CTL) tumor responses.1Finn O.J. dawn prevention.Nat. Rev. Immunol. 2018; 18: 183-194Crossref PubMed Scopus (95) Google Scholar,2Falzone L. Salomone S. Libra M. Evolution pharmacological treatments at turn third millennium.Front. Pharmacol. 9: 1300Crossref (243) Scholar As target antigens associated cells, approach can safer than other therapies avoiding off-target effects. evolved drugs immuno-oncology space, they comprise set antigens, adjuvants, vectors, methods.3Lopes A. Vandermeulen G. Préat V. Cancer DNA vaccines: current preclinical developments future perspectives.J. Exp. Clin. Res. 2019; 38: 146Crossref (108) Historically, hundreds TCV dozens pivotal were largely unsuccessful demonstrating clear benefit.4Rahma O.E. Gammoh E. Simon R.M. Khleif S.N. Is "3+3" dose-escalation phase I trial design suitable vaccine development? A recommendation alternative design.Clin. 2014; 20: 4758-4767Crossref (32) Scholar,5Tan A.C.L. Goubier Kohrt H.E. analysis 2 3 trial.J. Immunother. Cancer. 2015; 3: 48Crossref (21) This likely due not limited (1) suboptimal (2) lack effective (3) poorly immunogenic platforms, (4) an insufficient number CTLs entering immunosuppression related high disease burden, poor fitness, immunosuppressive microenvironment.6van der Burg S.H. Correlates activity novel vaccines.Semin. 39: 119-136Crossref (28) Scholar,7Tran T. Blanc C. Granier Saldmann Tanchot Tartour vaccine: building from lessons past.Semin. Immunopathol. 41: 69-85Crossref Renewed investment now underway, advanced platforms. Among recent advances neoantigen-based selective individualized new approaches activities compared conventional shared antigens.8Wirth T.C. Kühnel F. Neoantigen Targeting—dawn era immunotherapy?.Front. 2017; 8: 1848Crossref (50) Scholar, 9Zhang X. Sharma P.K. Peter Goedegebuure Gillanders W.E. Personalized mutanome.Vaccine. 35: 1094-1100Crossref (43) 10Sahin U. Türeci Ö. immunotherapy.Science. 359: 1355-1360Crossref (343) Given neoantigen load has correlated response existing immunotherapies,11Desrichard Snyder Chan T.A. applications immunotherapy.Clin. 2016; 22: 807-812Crossref (136) Scholar,12Łuksza Riaz N. Makarov Balachandran V.P. Hellmann M.D. Solovyov Rizvi N.A. Merghoub Levine A.J. et al.A fitness model predicts tumour checkpoint blockade immunotherapy.Nature. 551: 517-520Crossref (292) compelling targets personalizing activity. More 799 global drug pipeline 2019, more 400 active trials.13Xin Yu J. Hubbard-Lucey V.M. Tang Immuno-oncology goes global.Nat. Drug Discov. 899-900Crossref (94) Of these, least 23 vaccination approaches, which suited investigate therapeutically custom-tailored patients. aims provide detailed account components common mechanisms action TCVs, while focusing assessing landscapes, summarizing immunotherapies, obstacles development, regulatory framework and, lastly, providing insight into additional aspects important TCVs. Many biology relevant also apply successfully induce responses human body, act exploit immunity, priming activation, recognition effector eliminate cells.14Chen D.S. Mellman I. Oncology meets immunology: cancer-immunity cycle.Immunity. 2013; 1-10Abstract Full Text PDF (2786) engage both innate adaptive immunity use adjuvant trigger response, respectively. Nonspecific activated via pattern receptors, such Toll-like recognize respond pathogen- damage-associated molecular patterns. Engagement receptors activates transcription factor nuclear κB (NF-κB), stimulates cytokine chemokine production, recruits lymphocytes.15Rezaei Keshavarz-Fathi Vaccines Immunotherapy: An Evidence-Based Review Current Status Future Perspectives. Academic Press, 2018Google CTL-mediated assist presentation antigen-presenting (APCs); recruitment, processing, maturation APCs; induced expression costimulatory signals cytokines interaction APCs system prime cells; (5) localization elements tumor.16Song Q. Zhang C.D. Wu X.H. initial findings prospects.Immunol. Lett. 196: 11-21Crossref (36) 17Coventry B.J. immunomodulation: forming basis all immunotherapy.Ther. Adv. 7 (2515135519862234)PubMed 18Zhang Shi Z. Xu Mi influence microenvironment immunotherapy.FEBS 286: 4160-4175Crossref (35) schematic provided Figure 1. Through processes generate long-lasting immunological memory capable controlling growth inhibiting relapse metastasis. In studies, it shown long-lived regenerate cells.19Romero P. Banchereau Bhardwaj Cockett Disis M.L. Dranoff Gilboa Hammond S.A. Hershberg R. Korman al.The project: roadmap development.Sci. Transl. Med. 334ps9Crossref (107) Unfortunately, rarely met criteria biological engaged efficacious; however, hold promise improved performance.20Wong K.K. Li W.A. Mooney D.J. Advances vaccines.Adv. 130: 191-249Crossref (66) tumor-associated CTLs, thus expressed surface may strategy. choice major determinant immunogenicity takes advantage distinctions between normal cells. Numerous used identify one TCV. These include selection overexpressed dysregulated proteins, melanoma gene (MAGE), New York esophageal squamous carcinoma 1 (NY-ESO01), epidermal receptor (HER2) cancer-associated arise mutations found specific Scholar,21Jäger D. Jäger Knuth Immune antigens: implications immunotherapy cancer.J. Pathol. 2001; 54: 669-674Crossref (149) date directed first type, i.e., malignant lower levels healthy tissues.1Finn play complex helper role orchestrating regulating (boosting function, magnitude, quality, persistence, memory); additionally, protective through secretion, activation tumoricidal macrophages.22Pardoll D.M. Topalian S.L. antitumor immunity.Curr. Opin. 1998; 10: 588-594Crossref (563) 23Borst Ahrends Bąbała Melief C.J.M. Kastenmüller W. immunology immunotherapy.Nat. 635-647Crossref (391) 24Tay R.E. Richardson E.K. Toh H.C. Revisiting immunotherapy-new insights old paradigms.Cancer Gene Ther. 2020; (Published online May 24, 2020)https://doi.org/10.1038/s41417-020-0183-xCrossref Interferon (IFN)-γ release required elimination cells25Mumberg Monach P.A. Wanderling Philip Toledano A.Y. Schreiber R.D. H. MHC II-negative vivo indirect effects IFN-γ.Proc. Natl. Acad. Sci. USA. 1999; 96: 8633-8638Crossref (295) Scholar,26Alspach Lussier γ its roles promoting spontaneous immunity.Cold Spring Harb. Perspect. Biol. 11: a028480Crossref (104) attack tumors depend depletion either subset limiting inhibition.27Alspach Miceli A.P. Kizhvatov DuPage Luoma A.M. Meng Lichti C.F. Esaulova Vomund A.N. al.MHC-II shape 574: 696-701Crossref (219) Mechanistic crosstalk subsets, work optimize modulate crucial determinants TCVs.27Alspach 28Sillito Holler Stauss H.J. Engineering immunity.Cells. 1721Crossref 29Knutson K.L. Tumor immunotherapy.Cancer 2005; 721-728Crossref (487) 30Ostroumov Fekete-Drimusz Saborowski Woller CD4 CD8 interplay growth.Cell. Mol. Life 75: 689-713Crossref (166) 31Kreiter Vormehr van de Roemer Diken Löwer Diekmann Boegel Schrörs B. Vascotto Castle J.C. al.Mutant II epitopes drive cancer.Nature. 520: 692-696Crossref (640) currently rely various methods delivery, cell-based, protein/peptide-based, RNA- DNA-based, viral/bacterial-based Each considerations manufacturing, selection, immunogenicity, tolerability.1Finn wide spectrum adjuvants responses.32Temizoz Kuroda Ishii K.J. Vaccine immunotherapeutics.Int. 28: 329-338Crossref (138) contain attributes produce alone succeed increasing cell-mediated amplitude, specificity, profile, some optimized preclinically.32Temizoz Scholar,33Vermaelen K. improve anti-cancer cellular responses.Front. 8Crossref (69) damage- pathogen-associated initiating cascade aiding APCs. multitude engineering, packaging, conjunction biology, give rise great comparing systematically. Neoantigen-based tumor-specific therapies,34Schumacher T.N. Scheper Kvistborg neoantigens.Annu. 37: 173-200Crossref (176) typically each patient. confirm non-synonymous somatic inclusion TCV, biopsy tissue taken whole-exome RNA sequencing. Mutations analyzed using histocompatibility (MHC) epitope prediction algorithms prioritized. Ranked lists candidate further based vitro binding assay results synthetic peptides tested appropriate leukocyte allele interest.9Zhang Selected hence, unlike neoantigen-specific less eliminated during self-tolerance. enhances their ability stimulate robust increases breadth diversity response.8Wirth Various types variant targeted single nucleotide variants resulting change base another, indels insertion deletion sequence nucleotides genome frameshift mutation alter protein function. Neoantigens selected clonal origin present subclonal, only subset, immunoreactivity.35McGranahan Furness A.J.S. Rosenthal Ramskov Lyngaa Saini S.K. Jamal-Hanjani Wilson G.A. Birkbak N.J. Hiley C.T. al.Clonal immunoreactivity sensitivity blockade.Science. 351: 1463-1469Crossref (1632) classified growth, passenger lacking intrinsic advantages, driver advantages evolution, incorporated TCVs.36Aurisicchio Pallocca Ciliberto Palombo perfect therapy: neoantigens.J. 86Crossref (44) Patients harbor extensive variability clonality gives evasion effectors formation resistance mechanisms, reducing efficacy TCVs.37Morris L.G. Desrichard Şenbabaoğlu Y. Hakimi A.A. Reis-Filho J.S. Pan-cancer intratumor heterogeneity prognostic survival.Oncotarget. 7: 10051-10063Crossref (150) Scholar,38Shembrey Huntington N.D. Hollande Impact response.Cancers (Basel). 1217Crossref Tumors intratumoral higher degree branched increased amount subclones neoantigens, weaker responses.39Fennemann F.L. Vries I.J.M. Figdor C.G. Verdoes Attacking sides: multiplex tackle heterogeneity.Front. 824Crossref (22) Provided infiltration effect percentage expressing fractions subclonal had negative immunotherapy.35McGranahan Innovative multi-epitope multiplexed addition multi-regional sampling temporal changes following longitudinal liquid follow-up combating heterogeneity,39Fennemann Scholar,40Stanta Jahn S.W. Bonin Hoefler Tumour heterogeneity: principles practical consequences.Virchows Arch. 469: 371-384Crossref allowing dominant low-abundance reactivity. Following vaccination, augmentation CTL spread leads distinct untargeted cryptic reported mouse cancers.31Kreiter Scholar,41GuhaThakurta Sheikh Fan L.Q. Kandadi Meagher Hall S.J. Kantoff P.W. Higano C.S. Small E.J. Gardner al.Humoral nontargeted after treatment sipuleucel-t association outcome.Clin. 21: 3619-3630Crossref (85) 42Corbière Chapiro Stroobant Ma Lurquin Lethé Baren Van den Eynde Boon Coulie P.G. Antigen spreading contributes MAGE vaccination-induced regression metastases.Cancer 2011; 71: 1253-1262Crossref (135) 43Disis Gooley Rinn Davis Piepkorn Cheever M.A. Knutson Schiffman Generation T-cell HER-2/neu immunization vaccines.J. Oncol. 2002; 2624-2632Crossref (372) 44Butterfield L.H. Ribas Dissette V.B. Amarnani Vu H.T. Oseguera Wang Elashoff McBride W.H. Mukherji al.Determinant dendritic cell-based melanoma.Clin. 2003; 998-1008PubMed 45Wierecky Müller M.R. Wirths Halder-Oehler Dörfel Schmidt S.M. Häntschel Brugger Schröder Horger M.S. al.Immunologic vaccinations peptide-pulsed metastatic renal patients.Cancer 2006; 66: 5910-5918Crossref (191) become control protection heterogeneous robust, durable, process broadens expands over time.46Gulley J.L. Madan R.A. Pachynski Mulders Trager Drake Role distinctive characteristics treatment.J. Inst. 109: djw261Crossref (102) Correlations show significant value diversification therapies.47Ribas Timmerman J.M. Butterfield Economou Determinant immunotherapy.Trends 24: 58-61Abstract (89) Foundational pre-clinical led proof-of-concept study mice, revealed mice treated mLama4 mAlg8 poly(IC) conferred strong rates animals.48Gubin M.M. Schuster Caron Ward J.P. Noguchi Ivanova Hundal Arthur Krebber W.J. al.Checkpoint tumour-specific mutant antigens.Nature. 515: 577-581Crossref (1259) Further supportive efforts models since confirmed novo inducing rejection aggressive conferring survival benefit.49Duperret Perales-Puchalt Stoltz G H Mandloi Barlow Chaudhuri Sardesai N.Y. Weiner D.B. multi-neoantigen drives predominately challenge.Cancer 174-182Crossref established patients melanoma, later glioblastoma, validating benefit even curative therapies.50Carreno B.M. Magrini Becker-Hapak Kaabinejadian Petti Ly Lie W.R. Hildebrand Mardis E.R. 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Quant. 81: 105-111Crossref (13) Scholar,55Bräunlein Krackhardt Identification characterization respective patients.Front. 1702Crossref (29) entered space accelerated plans, despite considerable risk regarding best platform given unproven prediction. Additional questions remain around dosing, identifying setting.56Guo Lei anticance

Language: Английский

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Reversing T-cell Exhaustion in Cancer: Lessons Learned from PD-1/PD-L1 Immune Checkpoint Blockade

Cancer Immunology Research, Journal Year: 2021, Volume and Issue: 10(2), P. 146 - 153

Published: Dec. 22, 2021

Anti-PD-1/PD-L1 immune checkpoint blockade (ICB) therapy has revolutionized the treatment of many types cancer over past decade. The initial therapeutic hypothesis underlying mechanism anti-PD-1/PD-L1 ICB was built around premise that it acts locally in tumor, reversing exhaustion PD-1hiCD8+ T cells by "releasing brakes." However, recent studies have provided unprecedented insight into complexity within CD8+ T-cell pool tumor microenvironment (TME). Single-cell RNA sequencing and epigenetic profiling identified novel cell surface markers, revealing heterogeneity states classified as unique. Moreover, these highlighted following ICB, outside TME possess a differential capacity to respond, mobilize TME, seed an effective antitumor response. In aggregate, developments led reevaluation our understanding both mechanisms sites action therapy. Here, we discuss evidence for reversibility after its implication further development immunotherapy.

Language: Английский

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CD4 T-Cell Exhaustion: Does It Exist and What Are Its Roles in Cancer?

Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 27(21), P. 5742 - 5752

Published: June 14, 2021

Abstract In chronic infections and in cancer, persistent antigen stimulation under suboptimal conditions can lead to the induction of T-cell exhaustion. Exhausted T cells are characterized by an increased expression inhibitory markers a progressive hierarchical loss function. Although cancer-induced exhaustion CD8 has been well-characterized identified as therapeutic target (i.e., via checkpoint inhibition), in-depth analyses other immune cell types, including CD4 cells, is wanting. While perhaps attributable contextual discovery amidst viral infection, lack thorough inquiry into particularly surprising given their important role orchestrating responses through T-helper direct cytotoxic functions. Current work suggests that may indeed be prevalent, have implicated various disease pathologies, such likely clinically relevant. Defining phenotypic subsets how it influences severity will crucial understanding collective dysfunction variety pathologies. this review, we discuss mechanistic clinical evidence for cancer. Further insight derivation manifestation exhaustive processes could reveal novel targets abrogate cancer induce robust antitumor response.

Language: Английский

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Improving head and neck cancer therapies by immunomodulation of the tumour microenvironment

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 23(3), P. 173 - 188

Published: Dec. 1, 2022

Language: Английский

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Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers

Cancers, Journal Year: 2022, Volume and Issue: 14(7), P. 1681 - 1681

Published: March 25, 2022

Our body is constantly exposed to pathogens or external threats, but with the immune response that our can develop, we fight off and defeat possible attacks infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as existence of a tumour also cause system (IS) be put on alert. Indeed, link between immunology cancer evident these days, IS being used one important targets for treating cancer. able eliminate those abnormal damaged cells found in body, preventing uncontrolled proliferation lead However, several cases, escape IS. It has been observed cells, extracellular matrix, blood vessels, fat various molecules could support growth development. Thus, developing receives structural support, irrigation energy, among other resources, making its survival progression possible. All components accompany help survive grow are called microenvironment (TME). Given importance presence development process, review will focus TME: cells. Immune anti-tumour protecting us against cells; nevertheless, they behave pro-tumoural thus promoting survival. In review, pro-tumour immunity discussed. addition, TME influence dual effect analysed.

Language: Английский

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Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 40(8), P. 1250 - 1258

Published: March 24, 2022

Language: Английский

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