Prime and Pull of T cell Responses Against Cancer-exogenous Antigens is Effective Against CPI-resistant Tumors

Overview

Journal Mol Ther Oncol

Date 2024 Apr 10

PMID 38596303

Authors

Fulvia Troise

Guido Leoni

Emanuele Sasso

Mariarosaria Del Sorbo

Marialuisa Esposito

Giuseppina Romano

Simona Allocca

Guendalina Froechlich

Gabriella Cotugno

Stefania Capone

Antonella Folgori

Elisa Scarselli

Anna Morena DAlise

Alfredo Nicosia

Affiliations

Soon will be listed here.

Abstract

Neoantigen (neoAg)-based cancer vaccines expand preexisting antitumor immunity and elicit novel cancer-specific T cells. However, at odds with prophylactic vaccines, therapeutic antitumor immunity must be induced when the tumor is present and has already established an immunosuppressive environment capable of rapidly impairing the function of anticancer neoAg T cells, thereby leading to lack of efficacy. To overcome tumor-induced immunosuppression, we first vaccinated mice bearing immune checkpoint inhibitor (CPI)-resistant tumors with an adenovirus vector encoding a set of potent cancer-exogenous CD8 and CD4 T cell epitopes (Ad-CAP1), and then "taught" cancer cells to express the same epitopes by using a tumor-retargeted herpesvirus vector (THV-CAP1). Potent CD8 effector T lymphocytes were elicited by Ad-CAP1, and subsequent THV-CAP1 delivery led to a significant delay in tumor growth and even cure.

References

OHara G, Duncan C, Ewer K, Collins K, Elias S, Halstead F . Clinical assessment of a recombinant simian adenovirus ChAd63: a potent new vaccine vector. J Infect Dis. 2012; 205(5):772-81. PMC: 3274376. DOI: 10.1093/infdis/jir850. View

Olivo Pimentel V, Marcus D, van der Wiel A, Lieuwes N, Biemans R, Lieverse R . Releasing the brakes of tumor immunity with anti-PD-L1 and pushing its accelerator with L19-IL2 cures poorly immunogenic tumors when combined with radiotherapy. J Immunother Cancer. 2021; 9(3). PMC: 7944996. DOI: 10.1136/jitc-2020-001764. View

Rizvi N, Hellmann M, Snyder A, Kvistborg P, Makarov V, Havel J . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-8. PMC: 4993154. DOI: 10.1126/science.aaa1348. View

Yadav M, Jhunjhunwala S, Phung Q, Lupardus P, Tanguay J, Bumbaca S . Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature. 2014; 515(7528):572-6. DOI: 10.1038/nature14001. View

Sasso E, DAlise A, Zambrano N, Scarselli E, Folgori A, Nicosia A . New viral vectors for infectious diseases and cancer. Semin Immunol. 2020; 50:101430. DOI: 10.1016/j.smim.2020.101430. View

Bullock B, Kimball A, Poczobutt J, Neuwelt A, Li H, Johnson A . Tumor-intrinsic response to IFNγ shapes the tumor microenvironment and anti-PD-1 response in NSCLC. Life Sci Alliance. 2019; 2(3). PMC: 6537751. DOI: 10.26508/lsa.201900328. View

Gulley J, Madan R, Pachynski R, Mulders P, Sheikh N, Trager J . Role of Antigen Spread and Distinctive Characteristics of Immunotherapy in Cancer Treatment. J Natl Cancer Inst. 2017; 109(4). PMC: 5441294. DOI: 10.1093/jnci/djw261. View

DAlise A, Brasu N, De Intinis C, Leoni G, Russo V, Langone F . Adenoviral-based vaccine promotes neoantigen-specific CD8 T cell stemness and tumor rejection. Sci Transl Med. 2022; 14(657):eabo7604. PMC: 9844517. DOI: 10.1126/scitranslmed.abo7604. View

van Akkooi A, Haferkamp S, Papa S, Franke V, Pinter A, Weishaupt C . A Retrospective Chart Review Study of Real-World Use of Talimogene Laherparepvec in Unresectable Stage IIIB-IVM1a Melanoma in Four European Countries. Adv Ther. 2020; 38(2):1245-1262. PMC: 7889564. DOI: 10.1007/s12325-020-01590-w. View

10.

Sharma P, Allison J . The future of immune checkpoint therapy. Science. 2015; 348(6230):56-61. DOI: 10.1126/science.aaa8172. View

11.

Leoni G, DAlise A, Tucci F, Micarelli E, Garzia I, De Lucia M . VENUS, a Novel Selection Approach to Improve the Accuracy of Neoantigens' Prediction. Vaccines (Basel). 2021; 9(8). PMC: 8402534. DOI: 10.3390/vaccines9080880. View

12.

Leoni V, Vannini A, Gatta V, Rambaldi J, Sanapo M, Barboni C . A fully-virulent retargeted oncolytic HSV armed with IL-12 elicits local immunity and vaccine therapy towards distant tumors. PLoS Pathog. 2018; 14(8):e1007209. PMC: 6095629. DOI: 10.1371/journal.ppat.1007209. View

13.

Sharma P, Hu-Lieskovan S, Wargo J, Ribas A . Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017; 168(4):707-723. PMC: 5391692. DOI: 10.1016/j.cell.2017.01.017. View

14.

Tahtinen S, Feola S, Capasso C, Laustio N, Groeneveldt C, Ylosmaki E . Exploiting Preexisting Immunity to Enhance Oncolytic Cancer Immunotherapy. Cancer Res. 2020; 80(12):2575-2585. DOI: 10.1158/0008-5472.CAN-19-2062. View

15.

Sasso E, Froechlich G, Cotugno G, DAlise A, Gentile C, Bignone V . Replicative conditioning of Herpes simplex type 1 virus by Survivin promoter, combined to ERBB2 retargeting, improves tumour cell-restricted oncolysis. Sci Rep. 2020; 10(1):4307. PMC: 7062820. DOI: 10.1038/s41598-020-61275-w. View

16.

De Lucia M, Cotugno G, Bignone V, Garzia I, Nocchi L, Langone F . Retargeted and Multi-cytokine-Armed Herpes Virus Is a Potent Cancer Endovaccine for Local and Systemic Anti-tumor Treatment. Mol Ther Oncolytics. 2020; 19:253-264. PMC: 7658578. DOI: 10.1016/j.omto.2020.10.006. View

17.

Froechlich G, Gentile C, Infante L, Caiazza C, Pagano P, Scatigna S . Generation of a Novel Mesothelin-Targeted Oncolytic Virus and Implemented Strategies for Manufacturing. Int J Mol Sci. 2021; 22(2). PMC: 7825047. DOI: 10.3390/ijms22020477. View

18.

Mao T, Israelow B, Pena-Hernandez M, Suberi A, Zhou L, Luyten S . Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses. Science. 2022; 378(6622):eabo2523. PMC: 9798903. DOI: 10.1126/science.abo2523. View

19.

Menotti L, Nicoletti G, Gatta V, Croci S, Landuzzi L, De Giovanni C . Inhibition of human tumor growth in mice by an oncolytic herpes simplex virus designed to target solely HER-2-positive cells. Proc Natl Acad Sci U S A. 2009; 106(22):9039-44. PMC: 2684841. DOI: 10.1073/pnas.0812268106. View

20.

Froechlich G, Caiazza C, Gentile C, DAlise A, De Lucia M, Langone F . Integrity of the Antiviral STING-mediated DNA Sensing in Tumor Cells Is Required to Sustain the Immunotherapeutic Efficacy of Oncolytic Virus. Cancers (Basel). 2020; 12(11). PMC: 7698602. DOI: 10.3390/cancers12113407. View