Save PD-1 resistance! More effective regulation of adenosine pathway by CD39 antibody

Tumor immunotherapy is considered to be one of the most successful methods in the field of cancer treatment in recent years However, PD-1 / PD-L1 antibody can not escape the cycle of drug resistance Clinical trial data show that the effective rate of PD-1 / PD-L1 mAb in the treatment of tumor is about 20%, and in this part of the patients who benefit, 15% - 35% of the patients who use PD-1 / PD-L1 mAb for a period of time have a relapse of the disease, that is, drug resistance Drug resistance of PD-1 is a problem that scientists and pharmaceutical companies are concerned about and want to solve Recently, Tizona therapeutics published a new paper "targeting CD39 in cancer vaccines an extractable ATP and inflammatory driven tumor" online in cancer discovery This paper describes a new mechanism that can regulate adenosine pathway and activate anti-tumor immune response more effectively by using antibodies that block CD39, and help to reduce the drug resistance of PD-1 CD39 is a cell surface enzyme, which is highly expressed in tumor cells, depleted T cells and multiple suppressive cells It is the first step for tumor microenvironment (TME) to transform the immunostimulatory molecule ATP into immunosuppressive adenosine, which promotes tumor immune escape This paper explored the mechanism of CD39 antibody inhibiting the transformation of extracellular ATP (eATP) to AMP The potency and mechanism of anti-cd39 mAb were compared with other drugs targeting adenosine pathway by using the same gene and humanized tumor model This study found that blocking the enzyme activity of CD39 with anti-cd39 antibody can help immune cells immerse into T-cell poor tumors and save the resistance to PD-1 It has been proved that this activity is mediated by ATP signal transduction of P2X7 receptor and subsequent stimulation of inflammatory bodies Only by targeting CD39, can ATP stimulate the anti-tumor immunity driven by inflammatory bodies and prevent the production of immunosuppressive adenosine Ttx-030 is an anti-cd39 monoclonal antibody discovered by Tizona It is currently in cooperation with abbvie for phase 1 / 1b clinical research, as a single therapy in adults with advanced cancer or in combination with approved anti-PD-1 drugs and standard chemotherapy (nct03884556) Ttx-030 can inhibit the activity of CD39 Ttx-030 blocks the formation of extracellular adenosine, which can inhibit the effector cells in TME In addition to preventing the formation of inhibitory adenosine, ttx-030 also blocks the degradation of ATP and retains the ability of ATP to stimulate dendritic and myeloid cells, which are responsible for the activation of immune cells necessary for innate and adaptive immunity "A new paper published in cancer discovery demonstrates that CD39 is a key immunomodulatory switch in immunosuppressive tumor TME," said Scott Clarke, CEO of Tizona We are pleased to develop our first-class anti-cd39 antibody ttx-030, which may change the prognosis of cancer patients " Tizona Therapeutics Tizona is a private clinical phase immunotherapy company dedicated to the development of first-class drugs that bring transformative benefits to cancer patients Tizona develops biotherapy to stimulate the immune system and resist immunosuppression by applying novel human biological insights, so as to solve the progression and recurrence of cancer Although the immunotherapy company is not so famous, its investors are not small MPM capital is a healthcare investment company with more than 20 years of experience in the establishment and investment of life science companies; Canaan is also a well-known early venture capital company; abinworth has invested in biotechnology for decades Targeting CD39 is a promising method to regulate adenosine pathway in TME to stimulate the immune system and fight immunosuppression Tizona's paper has proved that exploring the tumor microenvironment as a target source for tumor growth has great prospects We are also looking forward to more progress of ttx-030.