PD-L1 + TIGIT

Discover what’s next in cancer immunotherapy research

Explore one of the promising new targets

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PD-L1 + TIGIT

Discover what’s next in cancer immunotherapy research

Explore one of the promising new targets

Go to intro
Hero

TIGIT: An emerging inhibitor of antitumor response1

TIGIT is a novel co-inhibitory immune checkpoint that blocks anti tumor response. Targeting TIGIT and PD-L1 restores multiple steps in the cancer immunity cycle, offering a differentiated mechanism compared to blocking other clinically validated checkpoints, potentially leading to improved clinical outcomes1, 4

See how TIGIT works to disrupt critical cancer-immunity processes and how dual inhibition with PD-L1 may restore antitumor response.

TIGIT and PD-L1 co- blockade may lead to enhanced long- term tumor control in more patients than PD-(L)1 inhibition alone2-4

  • Tumor specific, long-lived cells associated with durable disease control expand to deliver an improved high quality anti-tumor immune response
  • The tumor microenvironment is reshaped to facilitate antitumor T cell activity

TIGIT is a co-inhibitory immune checkpoint that blocks antitumor response1,5-8

A novel target to help restore immune response3,4
  • Expressed on tumor-infiltrating T cells and natural killer cells, which are the primary drivers of antitumor response7
  • Plays a role in a variety of solid and hematologic malignancies6,7
TIGIT disrupts the cancer immune response by:
  • Suppressing T cell–mediated tumor killing1,7
  • Altering T cell differentiation1,7
  • Inhibiting natural killer cell–mediated tumor killing1,7
  • Inducing immunosuppressive dendritic cells1,7
Targeting both TIGIT and PD-L1 may enhance the anti- tumor immune response seen with PD-(L)1 inhibition alone8-10
  • TIGIT and PD-L1 independently interact with CD226 and converge to block the costimulatory signal10
  • PD-1 activation also disrupts the activation of CD2268-10
  • Complementary inhibition of TIGIT and PD-L1 restores CD226 signalling and antitumor immune response8-10
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Despite monumental progress the full potential of cancer immunotherapy is yet to be realized, as sustained response and long-term survival outcomes are lacking for many patients. Novel combination approaches are needed to accelerate progress.1

Roche’s scientific leadership in cancer immunotherapy led to the discovery of TIGIT and the broadest aTIGIT clinical development program with > 3000 pts, across early and metastatic settings, in several types of cancer. 13
Initial results in both preclinical and clinical studies suggest enhanced anti tumor activity with the complementary inhibition of TIGIT and PD-L1, potentially leading to a novel well tolerated cancer immunotherapy combination for patients.6,8,11,12

CD226=cluster of differentiation 226; PD-1=programmed death receptor-1; PD-L1=programmed death-ligand 1; PVR=polio virus receptor; TIGIT=T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain.

References:

  1. Manieri NA, Chiang EY, Grogan JL. TIGIT: a key inhibitor of the cancer immunity cycle. Trends Immunol. 2017;38(1):20-28.
  2. Nutsch et al. TIGIT and PD-L1 co-blockade promotes functional differentiation and clonal expansion of antitumor CD8+ T cells resistant to exhaustion programming. SITC 2023, Abstract 579-B
  3. Nutsch et al, SITC 2023, poster: doi:10.1136/jitc-2023-SITC2023.0579-B
  4. Guan X et al, Anti-TIGIT antibody tiragolumab leverages myeloid cells and regulatory T cells to improve PD-L1 checkpoint blockage. Nature 2024; 1-10
  5. Harjunpää H, Guillerey C. TIGIT as an emerging immune checkpoint. Clin Exp Immunol. 2019;200(2):108-119.
  6. Ge Z, Peppelenbosch MP, Sprengers D, Kwekkeboom J. TIGIT, the next step towards successful combination immune checkpoint therapy in cancer. Front Immunol. 2021;12:699895. doi:10.3389/fimmu.2021.699895
  7. Rotte A, Sahasranaman S, Budha N. Targeting TIGIT for immunotherapy of cancer: update on clinical development. Biomedicines. 2021:9(9):1277. doi:10.3390/biomedicines9091277
  8. Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J Immunother Cancer. 2020;8(2):e000957. doi:10.1136/jitc-2020-000957
  9. Pauken KE, Wherry EJ. TIGIT and CD226: tipping the balance between costimulatory and coinhibitory molecules to augment the cancer immunotherapy toolkit. Cancer Cell. 2014;26(6):785-787.
  10. Banta KL, Xu X, Chitre AS, et al. Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8+ T cell responses. Immunity. 2022;55(3):512-526.e9. doi:10.1016/j.immuni.2022.02.005
  11. Johnston RJ, Comps-Agrar L, Hackney J, et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8+ T cell effector function. Cancer Cell. 2014;26(6):923-937.
  12. Roche data on file
  13. clintrials.gov