Heat ratio PD-1, CD19 target CAR-T, dual resistance, single resistance, ADC flowering.

In September last year, the American Cancer Institute (CRI) published a research paper named immune oncology drug development goals global on Nature Reviews Drug Discovery, which described the global overview of drug research and development in the field of tumor immunotherapy. In the past two years, CD19 has surpassed PD-1 and PD-L1, becoming the most popular immunooncology target, With the continuous popularity of CD19 targets, the diversity of targeted CD19 products has been enriched. Car-t, double antibody, monoclonal antibody, ADC and other therapies have been developed accordingly.} top 15 tumor immune drug targets car-t-kymriah and yescarta. Since the development of car-t therapy, CD19 has been the most popular target, and cd19-car-t therapy has achieved great results in hematological tumors.with the approval of two car-t therapies targeting CD19, kymyriah and yescarta, have been approved for the market, and the development enthusiasm of car-t therapy for this target has been pushed to a peak.and it is expected that four more cd19-car-t therapies will be introduced in this field in the near future.at the end of last year, Gilead's kit and Bristol Myers Squibb submitted Blas for cd19-car-t therapy-kte-x19 (for recurrent or refractory mantle cell lymphoma -- MCL) and lisocabtagene maraleuccel (for adult patients with R / R blbcl).the speed is very fast in China. At present, some pharmaceutical companies have applied for listing.on February 24, the State Drug Administration (nmpa) officially accepted the new drug marketing application (NDA) of yijiliansai injection of foscarnet for the treatment of adult patients with R / R blbcl after the second-line or above systematic treatment.two days ago (June 30), myjunol has also applied to nmpa for the listing of jwcar029 {ruijilansai injection (tentative)} for cd19-car-t therapy, and the indication is relapsed and refractory lymphoma.with the continuous participation of new players and the promotion of subsequent product listing, the market competition in this field has entered a white hot.compared with cd19-car-t, tafasitamab has entered the market, although the track of cd19-car-t is relatively cold.on June 11, the anti-CD19 monoclonal antibody of viela bio has been approved by FDA for the treatment of adult neuromyelitis optica spectrum disease (nmosd).another CD19 monoclonal antibody that will be available soon comes from tafasitamab of MorphoSys. Tafasitamab is a humanized Fc domain optimized monoclonal antibody targeting CD19, which was originally developed by xencor.since then, MorphoSys has obtained a global exclusive license from the company to develop and commercialize tafasitamab.MorphoSys modified the FC terminal of tafasitamab to enhance antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent phagocytosis (ADCP), so as to improve the key mechanism of killing tumor cells. It has been verified in preclinical models that tafasitamab binding to CD19 can directly induce apoptosis of cancer cells.previously, the overall response rate (ORR) and complete response rate (CR) were 60% and 43% respectively in a phase II study to evaluate the safety and efficacy of tafasitamab combined with nadudide in the treatment of R / R DLBCL; at the median follow-up of 17.3 months, the median progression free survival (PFS) was 12.1 months; the median duration of remission (DOR) was 21.7 months. At a median follow-up of 19.6 months, the 12-month survival rate was 73.3%.in addition, in another re mind study to verify the efficacy of the combination therapy, tafasitamab + lenalidomide combination therapy had a significant clinical advantage over lenalidomide monotherapy, with orr of 67.1% (vs 34.2%) and Cr of 39.5% (vs 11.8%).at present, tafasitamab has been accepted by FDA and EMA for marketing in the United States (March 2, 2020) and Europe (May 20, 2020), and combined with lenalidomide for the treatment of patients with recurrent or refractory diffuse large B-cell lymphoma (R / R DLBCL).tafasitamab also obtained the priority review right of FDA, which was shortened from 10 months to 6 months.on January 14, 2020, morphsys and Incyte reached a cooperation agreement of $900 million in advance and $1.1 billion in milestone payment to jointly develop and commercialize tafasitamab globally. Morphsys and Incyte will jointly commercialize in the United States and share the benefits and costs. Incyte has exclusive commercialization rights in the market outside the United States.double antibody: blincytocd19 × CD3. In fact, the double antibody is the earliest drug development targeting CD19.as early as 2014, blinctymomab, the first drug targeting CD19, was approved by FDA.blincyto is a bispecific antibody drug developed by Amgen based on bite? Technology to simultaneously target CD3 and CD19 for the treatment of acute B-lymphoblastic leukemia.in October last year, blinatumomab was also listed in China.} blinatumomab double antibody principle another CD3 × CD19 double antibody, a-319, is designed and developed based on the immune therapeutic antibody platform (itabtm) independently developed by Jianneng long.a-319 binds to B tumor cell surface antigen CD19 and T cell antigen CD3 respectively through two functional regions, forming synapses between T cells and tumor cells, thus activating T cells and causing tumor cells to dissolve and die.in November 2018, the ind of a-319 was approved by nmpa, and the clinical trial of a-319 was officially started in April 2019.mechanism of action of itab CD47 × cd19tg-1801 is the first bispecific anti-CD47 / CD19 antibody, which is a completely humanized IgG1.in addition to retaining the beneficial characteristics of conventional CD47 monoclonal antibody, tg-1801 also added a double specificity function to improve its specificity and safety.tg-1801 can effectively provide anti-B-cell tumor phagocytosis activity and avoid the toxicity problems related to previous drugs targeting CD47 pathway.in addition, the common targeting of CD47 and CD19 not only enhances the expected safety, but also induces antibody dependent cytotoxicity (ADCC) by retaining its IgG1 Fc function, providing a second mechanism of antitumor activity.on June 17, 2019, TG therapeutics announced new results from preclinical data of tg-1801.for the first time, the company demonstrated the synergistic effect of tg-1801 combined with subluximab (the company's anti-CD20 monoclonal antibody) and umbralisib (the company's PI3K delta inhibitor) in the anti-CD47 / CD19 bispecific antibody.in addition, Roche's 4-1BB / CD19 double antibody, ro7227166, is also used in the treatment of refractory / recurrent non Hodgkin's lymphoma. phase I / II clinical study of CD19 / CD22 bispecific antibody oxs-1550 in the treatment of leukemia and lymphoma was carried out in cooperation with the Freemasonry cancer center of the University of Minnesota. ADC -- loncastuximab teirine is an antibody drug conjugate (ADC) formed by coupling a humanized monoclonal antibody targeting CD19 with cytotoxin pyrrolo benzodiazepine (PBD) dimer Teserine is internalized and absorbed by cancer cells, and then releases toxic warheads to kill cancer cells. at present, adct-402 is in the phase II clinical trial of R / R DLBCL. } adct-402 has been used as a single drug in clinical trials. At present, longcastuximab teirine is still in phase IB clinical trials in combination with ibrutinib in the treatment of R / R DLBCL or mantle cell lymphoma (MCL) and with durvalumab in the treatment of R / rdlbcl, MCL and follicular lymphama. recently, adct-402 has been approved by FDA as an orphan drug for R / R DLBCL and MCL. recently (January 10, 2020), ADC therapeutics announced that loncastuximab teserine can be used to treat relapsed or refractory diffuse large B-cell lymphoma (R / R) The overall response rate (ORR) was 45.5% (66 / 145), including 20% complete remission and 25.5% partial response, indicating controllable toxicity. the above mini series only introduces several representative products with the fastest progress in the treatment of CD19, such as car-t, double antibody, monoclonal antibody and ADC. There are also many other products under research. However, according to the current situation of CD19 target layout, the development heat is basically comparable to PD-1. It can be predicted that with the expansion of the benefit of tumor patients from the treatment of CD19 targeted drugs, pharmaceutical companies will love CD19 The degree will not diminish. summary: Although targeted CD19 drugs were approved for marketing in 2014, CD19 has not received enough attention to be widely developed and applied. The success of car technology has made CD19 one-stop famous, and major pharmaceutical companies around the world have invested in the development of car-t therapy. now, CD19 monoclonal antibody is also following the pace of big brother, and is about to compete with him on the same stage. Later, the formation of double antibody and ADC combined with other targets has been set up, and will soon be on the stage of tumor immunotherapy. recommended reading: 1. The first CD19 monoclonal antibody will be launched soon, and car-t market will meet competitors. 2. Bosheng ji'anke cd19-car-t therapy has been officially approved by nmpa. 3. The application for marketing permission of CD19 monoclonal antibody tafasitamab has been accepted by EMA. 4. Car-t meets the strong enemy! CD19 monoclonal antibody tafasitamab has been submitted for marketing application. 5. Stancel's "PD-1 inhibition" cd19-car-t cell therapy has been approved in the United States. 6. Following up with Novartis kymriah's steps, the first car-t therapy will be introduced for mantle cell lymphoma patients, and kit company has submitted a BLA listing application. 8. MD Anderson Cancer Center: targeting CD19 allogeneic car-nk cells The clinical results of the new generation of PBD toxic warhead ADC targeting CD19 were better than expected. 10. Ash: the complete remission rate of genhi cd19-car-t was 97.1%, and the double target CD19 & amp; cd19-car-t had a complete remission rate of 97.1%; The complete remission rate of cd22-car-t reached 93.8% with reference to 1.10.1038/d41573-019-00167-92. Please contact wechat: wz910605 for contribution / reprint of press copyright statement of each company. Business cooperation contact: welcome to forward and share. If any other media or website needs to reprint or quote all the copyright content of this website, it must be authorized and marked "transferred from: biopharmaceutical monograph" in an eye-catching position.