The Journal of Practical Medicine >
Immunotherapy based on neoantigen： A personalized treatment strategy for melanoma
Received date: 2023-10-21
Online published: 2024-05-21
Immune checkpoint inhibitors have significantly improved the prognosis of patients with melanoma， but primary and acquired resistance have led to a bottleneck in treatment. The binding of T-cell receptors to tumor antigens is the key point for immunotherapy. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations. Neoantigens， identifiable as foreign entities， have the capacity to initiate an immune response unfettered by central and peripheral tolerance mechanisms. This distinctive characteristic renders them highly promising targets in the realm of cancer therapy. Vaccines targeting tumor neoantigens， adoptive cell transfer， and antibody-based therapies can effectively enhance and expand tumor-specific immune responses， promoting T-cell recognition and elimination of tumors， thereby breaking through current treatment bottlenecks. This article discusses the current status， recent advancements， clinical challenges， and future directions in the personalized treatment of melanoma based on neoantigens.
Key words： melanoma; neoantigen; immunotherapy
Xizhi WEN , Xiaoshi. ZHANG . Immunotherapy based on neoantigen： A personalized treatment strategy for melanoma[J]. The Journal of Practical Medicine, 2024 , 40(10) : 1331 -1337 . DOI: 10.3969/j.issn.1006-5725.2024.10.001
| 1 | CURTI B D， FARIES M B. Recent Advances in the Treatment of Melanoma［J］. N Engl J Med， 2021， 384（23）：2229-2240. doi:10.1056/nejmra2034861 |
| 2 | LARKIN J， CHIARION-SILENI V， GONZALEZ R， et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma［J］. N Engl J Med， 2019， 381（16）：1535-1546. doi:10.1056/nejmoa1910836 |
| 3 | OLIVEIRA G， STROMHAUG K， KLAEGER S， et al. Phenotype， specificity and avidity of antitumour CD8（+） T cells in melanoma［J］. Nature， 2021， 596（7870）：119-125. doi:10.1038/s41586-021-03704-y |
| 4 | KIM J M， CHEN D S. Immune escape to PD-L1/PD-1 blockade： seven steps to success （or failure）［J］. Ann Oncol， 2016， 27（8）：1492-1504. doi:10.1093/annonc/mdw217 |
| 5 | VESELY M D， ZHANG T， CHEN L. Resistance Mechanisms to Anti-PD Cancer Immunotherapy［J］. Annu Rev Immunol， 2022， 40：45-74. doi:10.1146/annurev-immunol-070621-030155 |
| 6 | DESAI R， COXON A T， DUNN G P. Therapeutic applications of the cancer immunoediting hypothesis［J］. Semin Cancer Biol， 2022， 78：63-77. doi:10.1016/j.semcancer.2021.03.002 |
| 7 | GHORANI E， SWANTON C， QUEZADA S A. Cancer cell-intrinsic mechanisms driving acquired immune tolerance［J］. Immunity， 2023， 56（10）：2270-2295. doi:10.1016/j.immuni.2023.09.004 |
| 8 | SUN Q， HONG Z， ZHANG C， et al. Immune checkpoint therapy for solid tumours： clinical dilemmas and future trends［J］. Signal Transduct Target Ther， 2023， 8（1）：320. doi:10.1038/s41392-023-01522-4 |
| 9 | CHANDRAN S S， KLEBANOFF C A. T cell receptor-based cancer immunotherapy： Emerging efficacy and pathways of resistance［J］. Immunol Rev， 2019， 290（1）：127-147. doi:10.1111/imr.12772 |
| 10 | SCHUMACHER T N， SCHREIBER R D. Neoantigens in cancer immunotherapy［J］. Science， 2015， 348（6230）：69-74. doi:10.1126/science.aaa4971 |
| 11 | WACH M M， SUBJECK J R， WANG X Y， et al. Recombinant human Hsp110-gp100 chaperone complex vaccine is nontoxic and induces response in advanced stage melanoma patients［J］. Melanoma Res， 2022， 32（2）：88-97. doi:10.1097/cmr.0000000000000796 |
| 12 | GORDY J T， LUO K， ZHANG H， et al. Fusion of the dendritic cell-targeting chemokine MIP3α to melanoma antigen Gp100 in a therapeutic DNA vaccine significantly enhances immunogenicity and survival in a mouse melanoma model［J］. J Immunother Cancer， 2016， 4：96. doi:10.1186/s40425-016-0189-y |
| 13 | YAN J， TINGEY C， LYDE R， et al. Novel and enhanced anti-melanoma DNA vaccine targeting the tyrosinase protein inhibits myeloid-derived suppressor cells and tumor growth in a syngeneic prophylactic and therapeutic murine model［J］. Cancer Gene Ther， 2014， 21（12）：507-517. doi:10.1038/cgt.2014.56 |
| 14 | GROB J J， MORTIER L， D'HONDT L， et al. Safety and immunogenicity of MAGE-A3 cancer immunotherapeutic with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma： an open phase I/II study with a first assessment of a predictive gene signature［J］. ESMO Open， 2017， 2（5）：e000203. doi:10.1136/esmoopen-2017-000203 |
| 15 | DRENO B， THOMPSON J F， SMITHERS B M， et al. MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected， MAGE-A3-positive， stage Ⅲ melanoma （DERMA）： a double-blind， randomised， placebo-controlled， phase 3 trial［J］. Lancet Oncol， 2018， 19（7）：916-929. doi:10.1016/s1470-2045(18)30254-7 |
| 16 | SCHWARTZENTRUBER D J， LAWSON D H， RICHARDS J M， et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma［J］. N Engl J Med， 2011， 364（22）：2119-2127. doi:10.1056/nejmoa1012863 |
| 17 | XIE N， SHEN G， GAO W， et al. Neoantigens： promising targets for cancer therapy［J］. Signal Transduct Target Ther， 2023， 8（1）：9. doi:10.1038/s41392-022-01270-x |
| 18 | YARCHOAN M， JOHNSON B A 3rd， LUTZ E R， et al. Targeting neoantigens to augment antitumour immunity［J］. Nat Rev Cancer， 2017， 17（4）：209-222. doi:10.1038/nrc.2016.154 |
| 19 | LI J， XIAO Z， WANG D， et al. The screening， identification， design and clinical application of tumor-specific neoantigens for TCR-T cells［J］. Mol Cancer， 2023， 22（1）：141. doi:10.1186/s12943-023-01844-5 |
| 20 | PERI A， SALOMON N， WOLF Y， et al. The landscape of T cell antigens for cancer immunotherapy［J］. Nat Cancer， 2023， 4（7）：937-954. doi:10.1038/s43018-023-00588-x |
| 21 | TURAJLIC S， LITCHFIELD K， XU H， et al. Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype： a pan-cancer analysis［J］. Lancet Oncol， 2017， 18（8）：1009-1021. doi:10.1016/s1470-2045(17)30516-8 |
| 22 | TEIXIDO C， CASTILLO P， MARTINEZ-VILA C， et al. Molecular Markers and Targets in Melanoma［J］. Cells， 2021， 10（9）：2320. doi:10.3390/cells10092320 |
| 23 | YARCHOAN M， HOPKINS A， JAFFEE E M. Tumor Mutational Burden and Response Rate to PD-1 Inhibition［J］. N Engl J Med， 2017， 377（25）：2500-2501. doi:10.1056/nejmc1713444 |
| 24 | GONZáLEZ F E， GLEISNER A， FALCóN-BEAS F， et al. Tumor cell lysates as immunogenic sources for cancer vaccine design［J］. Hum Vaccin Immunother， 2014， 10（11）：3261-3269. doi:10.4161/21645515.2014.982996 |
| 25 | LIPSON E J， SHARFMAN W H， CHEN S， et al. Safety and immunologic correlates of Melanoma GVAX， a GM-CSF secreting allogeneic melanoma cell vaccine administered in the adjuvant setting［J］. J Transl Med， 2015， 13：214. doi:10.1186/s12967-015-0572-3 |
| 26 | KATSIKIS P D， ISHII K J， SCHLIEHE C. Challenges in developing personalized neoantigen cancer vaccines［J］. Nat Rev Immunol， 2024，24（3）：213-227. doi:10.1038/s41577-023-00937-y |
| 27 | D'ALISE A M， SCARSELLI E. Getting personal in metastatic melanoma： neoantigen-based vaccines as a new therapeutic strategy［J］. Curr Opin Oncol， 2023， 35（2）：94-99. doi:10.1097/cco.0000000000000923 |
| 28 | BAFALOUKOS D， GAZOULI I， KOUTSERIMPAS C， et al. Evolution and Progress of mRNA Vaccines in the Treatment of Melanoma： Future Prospects［J］. Vaccines （Basel）， 2023， 11（3）：636. doi:10.3390/vaccines11030636 |
| 29 | CARRENO B M， MAGRINI V， BECKER-HAPAK M， et al. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells［J］. Science， 2015， 348（6236）：803-808. doi:10.1126/science.aaa3828 |
| 30 | ROSENBERG S A， PACKARD B S， AEBERSOLD P M， et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report［J］. N Engl J Med， 1988， 319（25）：1676-1680. doi:10.1056/nejm198812223192527 |
| 31 | ROSENBERG S A， YANG J C， SHERRY R M， et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy［J］. Clin Cancer Res， 2011， 17（13）：4550-4557. doi:10.1158/1078-0432.ccr-11-0116 |
| 32 | HE J， XIONG X， YANG H， et al. Defined tumor antigen-specific T cells potentiate personalized TCR-T cell therapy and prediction of immunotherapy response［J］. Cell Res， 2022， 32（6）：530-542. doi:10.1038/s41422-022-00627-9 |
| 33 | LI D， CHEN C， LI J， et al. A pilot study of lymphodepletion intensity for peripheral blood mononuclear cell-derived neoantigen-specific CD8+?T cell therapy in patients with advanced solid tumors［J］. Nat Commun， 2023， 14（1）：3447. doi:10.1038/s41467-023-39225-7 |
| 34 | MüLLER M， HUBER F， ARNAUD M， et al. Machine learning methods and harmonized datasets improve immunogenic neoantigen prediction［J］. Immunity， 2023， 56（11）：2650-2663.e6. doi:10.1016/j.immuni.2023.09.002 |
| 35 | RICKER C A， MELI K， VAN ALLEN E M. Historical perspective and future directions： computational science in immuno-oncology［J］. J Immunother Cancer， 2024， 12（1）：e008306. doi:10.1136/jitc-2023-008306 |
| 36 | CHONG C， COUKOS G， BASSANI-STERNBERG M. Identification of tumor antigens with immunopeptidomics［J］. Nat Biotechnol， 2022， 40（2）：175-188. doi:10.1038/s41587-021-01038-8 |
| 37 | HOENISCH GRAVEL N， NELDE A， BAUER J， et al. TOF（IMS） mass spectrometry-based immunopeptidomics refines tumor antigen identification［J］. Nat Commun， 2023， 14（1）：7472. doi:10.1038/s41467-023-42692-7 |
| 38 | ROESLER A S， ANDERSON K S. Beyond Sequencing： Prioritizing and Delivering Neoantigens for Cancer Vaccines［J］. Methods Mol Biol， 2022， 2410：649-670. doi:10.1007/978-1-0716-1884-4_35 |
| 39 | MINEGISHI Y， HAGA Y， UEDA K. Emerging potential of immunopeptidomics by mass spectrometry in cancer immunotherapy［J］. Cancer Sci， 2024. doi：10.1111/cas.16118 . |
| 40 | OTT P A， HU Z， KESKIN D B， et al. An immunogenic personal neoantigen vaccine for patients with melanoma［J］. Nature， 2017， 547（7662）：217-221. doi:10.1038/nature22991 |
| 41 | SAHIN U， DERHOVANESSIAN E， MILLER M， et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer［J］. Nature， 2017， 547（7662）：222-226. |
| 42 | WEBER J S， CARLINO M S， KHATTAK A， et al. Individualised neoantigen therapy mRNA-4157 （V940） plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma （KEYNOTE-942）： a randomised， phase 2b study［J］. Lancet， 2024， 403（10427）：632-644. doi:10.1016/s0140-6736(23)02268-7 |
| 43 | VAN DEN BERG J H， HEEMSKERK B， VAN ROOIJ N， et al. Tumor infiltrating lymphocytes （TIL） therapy in metastatic melanoma： boosting of neoantigen-specific T cell reactivity and long-term follow-up［J］. J Immunother Cancer， 2020， 8（2）：e000848. doi:10.1136/jitc-2020-000848 |
| 44 | SARNAIK A A， HAMID O， KHUSHALANI N I， et al. Lifileucel， a Tumor-Infiltrating Lymphocyte Therapy， in Metastatic Melanoma［J］. J Clin Oncol， 2021， 39（24）：2656-2666. doi:10.1200/jco.21.00612 |
| 45 | ROHAAN M W， BORCH T H， VAN DEN BERG J H， et al. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma［J］. N Engl J Med， 2022， 387（23）：2113-2125. |
| 46 | CAUSHI J X， ZHANG J， JI Z， et al. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers［J］. Nature， 2021， 596（7870）：126-132. doi:10.1038/s41586-021-03752-4 |
| 47 | KLEBANOFF C A， CHANDRAN S S， BAKER B M， et al. T cell receptor therapeutics： immunological targeting of the intracellular cancer proteome［J］. Nat Rev Drug Discov， 2023， 22（12）：996-1017. doi:10.1038/s41573-023-00809-z |
| 48 | GROENEVELDT C， KINDERMAN P， VAN DEN WOLLENBERG D， et al. Preconditioning of the tumor microenvironment with oncolytic reovirus converts CD3-bispecific antibody treatment into effective immunotherapy［J］. J Immunother Cancer， 2020， 8（2）：e001191. doi:10.1136/jitc-2020-001191 |
| 49 | GERBER H P， PRESTA L G. TCR mimic compounds for pHLA targeting with high potency modalities in oncology［J］. Front Oncol， 2022， 12：1027548. doi:10.3389/fonc.2022.1027548 |
| 50 | HASSEL J C， PIPERNO-NEUMANN S， RUTKOWSKI P， et al. Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma［J］. N Engl J Med， 2023， 389（24）：2256-2266. doi:10.1056/nejmoa2304753 |
| 51 | SHEN Y， WEI X， JIN S， et al. TCR-mimic antibody-drug conjugates targeting intracellular tumor-specific mutant antigen KRAS G12V mutation［J］. Asian J Pharm Sci， 2020， 15（6）：777-785. doi:10.1016/j.ajps.2020.01.002 |
| 52 | DOUGLASS J， HSIUE E H， MOG B J， et al. Bispecific antibodies targeting mutant RAS neoantigens［J］. Sci Immunol， 2021， 6（57）：eabd5515. doi:10.1126/sciimmunol.abd5515 |
| 53 | HSIUE E H， WRIGHT K M， DOUGLASS J， et al. Targeting a neoantigen derived from a common TP53 mutation［J］. Science， 2021， 371（6533）：eabc8697. doi:10.1126/science.abc8697 |
| 54 | SHI Y， JING B， XI R. Comprehensive analysis of neoantigens derived from structural variation across whole genomes from 2528 tumors［J］. Genome Biol， 2023， 24（1）：169. doi:10.1186/s13059-023-03005-9 |
| 55 | HUANG F， LI J， WEN X， et al. Next-generation sequencing in advanced Chinese melanoma reveals therapeutic targets and prognostic biomarkers for immunotherapy［J］. Sci Rep， 2022， 12（1）：9559. doi:10.1038/s41598-022-13391-y |
| 56 | MENG W， SCHREIBER R D， LICHTI C F. Recent advances in immunopeptidomic-based tumor neoantigen discovery［J］. Adv Immunol， 2023， 160：1-36. doi:10.1016/bs.ai.2023.10.001 |
| 57 | POOLE A， KARUPPIAH V， HARTT A， et al. Therapeutic high affinity T cell receptor targeting a KRAS（G12D） cancer neoantigen［J］. Nat Commun， 2022， 13（1）：5333. doi:10.1038/s41467-022-32811-1 |
| 58 | CHANDRAN S S， MA J， KLATT M G， et al. Immunogenicity and therapeutic targeting of a public neoantigen derived from mutated PIK3CA［J］. Nat Med， 2022， 28（5）：946-957. doi:10.1038/s41591-022-01786-3 |
| 59 | CROSBY E J， HARTMAN Z C， LYERLY H K. Beyond Neoantigens： Antigens Derived from Tumor Drivers as Cancer Vaccine Targets［J］. Clin Cancer Res， 2023， 29（17）：3256-3258. doi:10.1158/1078-0432.ccr-23-1244 |
| 60 | ZHANG R， TANG L， WANG Y， et al. A Dendrimer Peptide （KK2DP7） Delivery System with Dual Functions of Lymph Node Targeting and Immune Adjuvants as a General Strategy for Cancer Immunotherapy［J］. Adv Sci （Weinh）， 2023， 10（15）：e2300116. doi:10.1002/advs.202300116 |
| 61 | PANT S， WAINBERG Z A， WEEKES C D， et al. Lymph-node-targeted， mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer： the phase 1 AMPLIFY-201 trial［J］. Nat Med， 2024， 30（2）：531-542. doi:10.1038/s41591-023-02760-3 |
/
| 〈 |
|
〉 |