Combined Therapy of PD-1 and GITR

Introduction to Combined Therapy

There is no doubt that inhibitory immune checkpoints have made important advances in cancer treatment in the past decades. However, even if immune checkpoint inhibitors have dramatically changed the treatment status of multiple cancers, there are only a small percentage of patients can benefit from it. In the case of inefficient use of single immune checkpoint treatment, the combined therapy has been served as an extremely valuable path for cancer treatment.

Research for Combined Therapy of PD-1 and GITR

Programmed Death 1 (PD-1) protein is a key co-inhibitory receptor that inhibits the effector functions of activated T cells and avoids autoimmunity. The binding with its ligands PD-L1 (B7-H1) and PD-L2 (B7-DC) leads to the inhibition of both adaptive and innate immune responses. The recent clinical trials showed that the PD-1/PD-L1 pathway is a promising target for cancer immunotherapy. Glucocorticoid-induced TNFR related protein (GITR, also known as TNFRSF18) is a member of the TNF receptor family expressed on activated T cells, B cells, NK cells, myeloid cells, and regulatory T cells (Treg). As a co-stimulatory molecule, it is up-regulated on activated T cells and increases their proliferation, activation, and cytokine production. The combination of PD-1 blockade and GITR triggering would synergistically improve the effector functions of tumor-infiltrating T cells and increase the antitumor immunity.

In the ID8 murine ovarian cancer model and 4T1 breast cancer model, either single anti-PD-1 or anti-GITR mAb presented little antitumor effect, while combined therapy of PD-1 and GITR significantly prolonged the overall survival tie of mice. What's more, the weight of tumor masses greatly decreased compared with the single mAb treated group and the control group. The further data indicated that the combined therapy of PD-1 and GITR mounted an antitumor memory immune response in mice.

Proposed model for anti-PD-1 and anti-GITR Ab combination therapy. Fig.1 Proposed model for anti-PD-1 and anti-GITR Ab combination therapy. (Wang, B 2018)

Services at Creative Biolabs

Creative Biolabs is a leading service provider that focuses on combined therapy against multiple cancers. Based on our advanced drug discovery platform and extensive experience, now Creative Biolabs helps for combined therapy research of PD-1 and GITR against multiple cancers for our clients all over the world; the services we provide include but not limited to:

If you are interested in our services, please do not hesitate to contact us for more detailed information.

Reference

  1. Wang, B.; et al. Combination cancer immunotherapy targeting PD-1 and GITR can rescue CD8+ T cell dysfunction and maintain memory phenotype. Science immunology. 2018, 3(29).

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic, or any in vivo human use.