Non-small cell lung cancers
(NSCLCs) represent over 80% of all malignant lung tumours and are one of the
leading causes of cancer death throughout the
world. First- and second-line treatment of advanced or metastatic NSCLCs
has changed dramatically during the last two decades with the development of
novel immunotherapies (e.g., checkpoint inhibitors targeting PD-1, PD-L1, and
CTLA-4) sparing NSCLC patients from the toxic effects of chemotherapy. However,
only 15%-20% of all patients respond
to treatment. In order to improve response rates, experimental and clinical
evidence has provided the basis for further evaluating the combination of
co-stimulatory and inhibitory monoclonal antibodies to improve the anti-tumour
immune response. Innovative second- and third-generation immuno-oncology drugs
are currently evaluated in ongoing phase I-III trials (either alone or in
combination) including the new checkpoint inhibitor target TIGIT (T cell
immunoreceptor with Ig and ITIM domains). TIGIT functions as an inhibitory
immunoglobin receptor which is overexpressed by different immune cells
including effector and memory CD4+ T and CD8+ T cells,
regulatory T cells (Tregs), follicular T helper cells (Tfh),
and natural killer cells.Targeting
the interaction between the receptors of the
TIGIT receptors (e.g., CD96, CD112R, CD226, TIGIT and their
corresponding binding partners) has become an innovative strategy for the next
concepts of cancer immunotherapy that has the potential to synergize with
PD-1/PD-L1checkpoint inhibition. Currently, four anti-TIGIT monoclonal
antibodies are currently being studied in phase III trials in NSCLCs:
Dempke, W.C.M. and Fenchel, K. (2021) Has Programmed Cell Death Ligand-1 MET an Accomplice in Non-Small Cell Lung Cancer? A Narrative Review. Translational Lung Cancer Research, 10, 2667-2682. https://doi.org/10.21037/tlcr-21-124
[3]
Franklin, M.R., Platero, S., Saini, K.S., Curigliano, G. and Anderson, S. (2022) Immuno-Oncology Trends: Preclinical Models, Biomarkers, and Clinical Development. The Journal for ImmunoTherapy of Cancer, 10, e003231.
https://doi.org/10.1136/jitc-2021-003231
[4]
Marin-Acevedo, J.A., Dholaria, B., Soyano, A.E., Knutson, K.L., Chumsri, S. and Lou, Y. (2018) Next Generation of Immune Checkpoint Therapy in Cancer: New Developments and Challenges. Journal Hematology & Oncology, 11, 39-47.
https://doi.org/10.1186/s13045-018-0582-8
[5]
Mazzarella, L., Duso, B.A., Trapani, D., Belli, C., D’Amico, P., Ferraro, E., Viale, G. and Curigliano, G. (2019) The Evolving Landscape of ‘Next-Generation’ Immune Checkpoint Inhibition: A Review. European Journal of Cancer, 117, 14-31.
https://doi.org/10.1016/j.ejca.2019.04.035
[6]
Dempke, W.C.M., Fenchel, K., Uciechowski, P. and Dale, S.P. (2017) Second- and Third-Generation Drugs for Immune-Oncology Treatment—The More the Better? European Journal of Cancer, 74, 55-72. https://doi.org/10.1016/j.ejca.2017.01.001
[7]
Schreiber, R.D., Old, L.J. and Smyth, M.J. (2011) Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion. Science, 331, 1565-1570.
https://doi.org/10.1038/s41571-021-00552-7
[8]
Li, B., Chan, H.L. and Chen, P. (2019) Immune Checkpoint Inhibition: Basics and Challenges. Current Medicinal Chemistry, 26, 3009-3025.
https://doi.org/10.1038/s41571-021-00552-7
[9]
Kraehenbuehl, L., Weng, C.-H., Eghbali, S., Wolchok, J.D. and Merghoub, T. (2022) Enhancing Immunotherapy in Cancer by Targeting Emerging Immunomodulatory Pathways. Nature Reviews Clinical Oncology, 37, 50-57.
https://doi.org/10.1038/s41571-021-00552-7
[10]
Jin, H.-S. and Park, Y. (2021) Hitting the Complexity of the TIGIT-CD96-CD112R-CD226 Axis for Next-Generation Cancer Immunotherapy. BMB Reports, 54, 2-11.
https://doi.org/10.5483/BMBRep.2021.54.1.229
[11]
Annese, T., Tamma, R. and Ribatti, D. (2022) Update in TIGIT Immune-Checkpoint Role in Cancer. Frontiers in Oncology, 12, Article 871085.
https://doi.org/10.3389/fonc.2022.871085
[12]
Chiang, E.Y. and Mellman, I. (2022) TIGIT-CD226-PVR Axis: Advancing Immune Checkpoint Blockade for Cancer Immunotherapy. The Journal for ImmunoTherapy of Cancer, 4, e004711. https://doi.org/10.1136/jitc-2022-004711
[13]
Cho, B.C., Abreu, D.R., Hussein, M., Cobo, M., Patel, A.J., Secen, N., Lee, K.H., Massuti, B., Hiret, S., Yang, J.C.H., Barlesi, F., Lee, D.H., Ares, L.P., Hsieh, R.W., Patil, N.S., Twomey, P., Yang, X., Meng, R. and Johnson, K.L. (2022) Tiragolumab plus Atezolizumab versus Placebo plus Atezolizumab as a First-Line Treatment for PD-L1-Selected Non-Small-Cell Lung Cancer (CITYSCAPE): Primary and Follow-Up Analyses of a Randomized, Double-Blind, Phase 2 Trial. The Lancet Oncology, 6, 781-792. https://doi.org/10.1016/S1470-2045(22)00226-1
[14]
Sava, J. (2022) SKYSCRAPER-01 Trial Misses Co-Primary End Point of PFS in PD-L1-High NSCLC.
https://www.targetedonc.com/view/skyscraper-01-trial-misses-co-primary-end-point-of-pfs-in-pd-l1-high-NSCLC
[15]
Rudin, C.M., Liu, S.V., Lu, S., Soo, R.A., Hong, M.H., Lee, J.-S., Bryl, M, Dumoulin, D.W., Rittmeyer, A., Chiu, C.-H. Ozyilkan, O., Navarro, A., Novello, S., Ozwa, Y., Meng, R., Hoang, T., Lee, A., Wen, X., Huang, M. and Reck, M. (2022) SYKSCRAPER-02: Primary Results of a Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab (atezo) + Carboplatin + Etoposide (CE) with or without Tiragolumab (tira) in Patients (pts) with Untreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC). American Society of Clinical Oncology, 40, LBA8507. https://doi.org/10.1200/JCO.2022.40.17_suppl.LBA8507
[16]
Ahn, M.J., Niu, J., Kim, D.W., Chung, H.C., Vaishampayan, U.N., Maurice-Dror, C., Russo. P.L., Golan, T., Chartash, E. Chen, D., Healy, J., Rajasagi, M. and Lee, D.H. (2020) Vibostolimab, an Anti-TIGIT Antibody, as Monotherapy and in Combination with Pembrolizumab in Anti-PD-1/PD-L1-Refractory NSCLC. Annals of Oncology, 31, S887. https://doi.org/10.1016/j.annonc.2020.08.1714
[17]
Pelosci, A. (2021) Encouraging Overall Response Rate Reported with Domvanalimab-Combinations in Non-Small Cell Lung Cancer.
https://www.cancernetwork.com/view/encouraging-overall-response-rate-reported-with-domvanalimab-combinations-in-non-small-cell-lung-cancer
[18]
Vaena, D.A., Fleming, G.F., Chmielowski, B., Sharma, M., Hamilton, E.P., Sullivan, R.J., Shepard, D.R., Papadopoulos, K.P., Patnaik, A., ElNagger, A., Adewoye, A.H., Smith, R., Lim, E.A., Dumbrava, E.E. and Rasco, D.W. (2021) COM701 with or without Nivolumab: Results of an Ongoing Phase 1 Study of Safety, Tolerability and Preliminary Antitumor Activity in Patients with Advanced Solid Malignancies (NCT03667716). Journal of Clinical Oncology, 39, 2504.
https://doi.org/10.1200/JCO.2021.39.15_suppl.2504
