gotop

Uncovering the anti-cancer mechanisms of Immuno-Oncology

GNTbm-CC-02 has been developed through new formulation of GNTbm-CC-01. It possesses better PK profile and anti-cancer efficacy than GNTbm-CC-01. The anti-cancer mechanisms of GNTbm-CC-02 were similar to those of GNTbm-CC-01. However, as compared with GNTbm-CC-01, GNTbm-CC-02 has profoundly enhanced anti-cancer activity, which has been greatly reflected in the significant reduction of cell number and function of many  immunosuppressive cells and enhanced activation of CD8+T cells and NK cells for the killing of cancer cells. It will even remarkably produce memory T cells for effective surveillance and killing of cancer cells expressing the same antigen for T cell recognition in the host with complete response to the treatment, and therefore will induce permanent immune activity. The combination of GNTbm-CC-02 with immune checkpoint inhibitor will achieve synergistic effect of the anti-cancer activity and boost the immune response to an even higher rate.

GNTbm-CC-02 patent has been submitted for PCT application.
 

GNTbm-CC-02 overcomes the drug resistance issue caused by the first-line anti-PD-1 Ab treatment

GNTbm-CC-02 effectively improved the sensitivity of anti-cancer immune response to overcome the drug resistance problems caused by the use of anti-PD-1Ab in the first-line therapy. Although anti-PD-1 Ab has been approved for use in many cancer indications, most patients still have difficulty obtaining treatment benefits, with only about 20-30% of patients having a significant immune response and tumors shrinking. About 70-80% of patients will not obtain treatment benefits and will develop significant resistance to the first-line anti-PD-1 Ab treatment. These patients have difficulty to use anti-PD-1 or anti-PD-L1 Ab again for the therapy and require new regimens to help them battle the disease and obtain treatment benefits. Our studies found that GNTbm-CC-02 significantly increased the sensitivity in mice that developed resistance to the first-line anti-PD-1 Ab therapy and therefore improved the immune response rate. The combination of GNTbm-CC-02 with anti-CTLA-4 Ab had been demonstrated to obtain a very significant immune response rate for mice with resistance after first-line anti-PD-1 Ab therapy, and achieve significant inhibition of tumor growth.

GNTbm-CC-02 consists of new formulations of a novel epigenetic regulator and a generic drug C, components of GNTbm-CC-01. The newly formulated drugs in combination controlled the tumor microenvironment more efficiently with enhanced inhibition of immunosuppressive cells homing  to tumor site. These make GNTbm-CC-02 a powerful regimen to overcome the drug resistance issue caused by the first-line immune checkpoint inhibitor therapy or HPD (Hyperprogressive disease). 

Figure 2. GNTbm-CC-02 can overcome dug resistance caused by the first-line anti-PD-1 Ab treatment.

GNTbm-CC-02 overcomes the drug resistance issue caused by the first-line anti-PD-L1 Ab treatment

Although the drug resistance mechanisms caused by the first line anti-PD-L1 therapy are different to those of the first line anti-PD-1 Ab therapy, the treatment benefits with the first line anti-PD-L1 therapy are similar, with only about 20-30% of patients having a significant immune response and tumors shrinking. About 70-80% of patients will not obtain treatment benefits and will develop significant resistance to anti-PD-L1 Ab therapy. These patients have difficulty using anti-PD-1 or anti-PD-L1 Ab therapy for future therapy and require new regimens to help them battle the disease and obtain treatment benefits. Our studies found that GNTbm-CC-02 significantly increased the sensitivity in mice that developed resistance to the first-line anti-PD-L1 Ab therapy and therefore improved the immune response rate. The combination of GNTbm-CC-02 with anti-CTLA-4 Ab had been demonstrated to obtain a very significant immune response rate for mice with resistance after the first-line anti-PD-L1 Ab therapy, and achieve significant inhibition of tumor growth.

GNTbm-CC-02 consists of new formulations of a novel epigenetic regulator and a generic drug C, components of GNTbm-CC-01. The newly formulated drugs in combination controlled the tumor microenvironment more efficiently with enhanced inhibition of immunosuppressive cells homing  to tumor site. These make GNTbm-CC-02 a powerful regimen to overcome the drug resistance issue caused by the first-line immune checkpoint inhibitor therapy or HPD (Hyperprogressive disease). 

GNTbm-CC-02 controls the tumor microenvironment components including immunosuppressive cells such as Treg, M-MDSC, PMN-MDSC and TAM, through inhibition of all these cells it will contribute to the enhancement of sensitivity to anti-cancer immune response after occurrence of drug resistance to anti-PD-1/anti-PD-L1 Ab. Furthermore, when combined with anti-CTLA-4 Ab, GNTbm-CC-02 will significantly improve the immune response rate and survival.