Autocrine PD-1 antibody CAR-T therapy is out of the sheath: solid tumors are no longer forbidden | 2021CSCO famous doctor Kung Fu tea

*Only for medical professionals to read and refer to Professor Xu Qing as a guest doctor Kung Fu Tea, sharing the new breakthrough of autocrine PD-1 antibody CAR-T therapy in the treatment of solid tumors
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On February 18, 2021, Professor Xu Qing’s team from Shanghai Tenth People’s Hospital and Professor Qian Qijun’s team from Shanghai Cell Therapy Group published an article in the Journal of Cancer Immunotherapy (JITC) under the British Medical Journal (BMJ).
Autocrine PD-1 antibody chimeric antigen receptor T cell immunity (CAR-T) therapy for advanced refractory ovarian cancer [1], this case is currently the first in the world to use autocrine PD-1 antibody CAR- T therapy is used in the exploration of the clinical treatment of solid tumors
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The results show that CAR-T therapy not only has the function of simply killing tumor cells, but also can trigger a local tumor immune response, which can induce better and longer-lasting anti-tumor effects
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At the 2021 Chinese Society of Clinical Oncology (CSCO) annual meeting, "Medical Oncology Channel" invited Professor Xu Qing from Shanghai Tenth People's Hospital to be a guest doctor Kung Fu tea to talk about autocrine PD-1 antibody CAR-T therapy for advanced refractory Research progress of ovarian cancer and malignant pleural mesothelioma
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Prof.
Xu Qing (right) is a guest doctor Kung Fu Tea Scan the QR code to view the wonderful video.
Autocrine PD-1 antibody CAR-T therapy: Combination of two swords, force cutting of malignant tumors.
Ovarian cancer is the second leading cause of female deaths from gynecological tumors in the world
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Epithelial ovarian cancer (EOC) accounts for 90% of all ovarian malignancies, and 75% of patients are at an advanced stage at the time of diagnosis [1]
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For advanced refractory ovarian cancer, due to its immunosuppressive and pro-angiogenic tumor microenvironment, the available treatment options are limited and the curative effect is not good
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In recent years, CAR-T cell therapy has become a new star in the field of hematological tumors
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However, CAR-T cell therapy has been repeatedly frustrated in the field of solid tumors
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The high heterogeneity of solid tumors and the lack of good antigen targets are huge obstacles to their application in the field of solid tumors
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In addition, if CAR-T cell therapy acts on normal tissues off-target, it will cause serious adverse reactions
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Is there an antigen that can be highly expressed in tumor tissues and low in normal tissues, and can be used as a specific target for CAR-T applications in the field of solid tumors? Professor Xu Qing’s team found that mesothelin (MSLN) is such a target, which is highly expressed in ovarian cancer tissues and low in normal tissues, and may become an effective target for CAR-T applications in solid tumors
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Based on previous research results, Professor Xu Qing's team explored a new type of autocrine PD-1 antibody CAR-T therapy for advanced refractory ovarian cancer
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The study analyzed the efficacy of autocrine PD-1 antibody CAR-T therapy combined with apatinib in a case of advanced refractory ovarian cancer
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In terms of mechanism, the therapy has the dual anti-tumor effects of immune checkpoint inhibitors and CAR-T targeted therapy, while also improving the tumor microenvironment and inhibiting angiogenesis
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▌ The beginning of treatment for advanced refractory ovarian cancer and malignant pleural mesothelioma can be seen in the results of this clinical study.
After the use of autocrine PD-1 antibody CAR-T therapy, this patient with advanced refractory ovarian cancer not only There was a shrinkage of the lesion visible by imaging (Figure 1), and there were obvious changes in cytokines in the body (Figure 2)
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In terms of survival benefits, the patient's progression-free survival (PFS) and overall survival (OS) time reached 5 months and 17 months, respectively
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Figure 1: Comparison of imaging data of patients before and after treatment with autocrine PD-1 antibody CAR-T therapy Figure 2: Combination therapy use cycle, CAR-T cells and PD-1 antibodies, and changes in cytokines in the body Professor Qing Xu mentioned After the success in advanced refractory ovarian cancer, this treatment plan will be extended to other tumor types for exploration in the future.
For example, in the innovative drug session of the CSCO conference this year, the research team conducted autocrine PD-1 Antibody CAR-T therapy in the treatment of malignant pleural mesothelioma
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Can autocrine PD-1 antibody CAR-T therapy usher in a new era of diagnosis and treatment of malignant pleural mesothelioma? The incidence of malignant pleural mesothelioma is low.
According to the data in 2020, the global incidence of malignant pleural mesothelioma only accounts for 0.
2% of new malignant tumors [2]
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However, China's population base is large, there are many such patients, and the treatment options for advanced patients are limited
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Fortunately, malignant pleural mesothelioma, like advanced refractory ovarian cancer, is a tumor with high expression of mesothelin
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So, can autocrine PD-1 antibody CAR-T therapy achieve good results in malignant pleural mesothelioma? Preliminary clinical research results show that patients with malignant pleural mesothelioma after using autocrine PD-1 antibody CAR-T therapy in combination with apatinib, both safety and effectiveness have reached the investigator's expected results
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In the future, whether autocrine PD-1 antibody CAR-T therapy can be combined with other tumor treatment methods to achieve greater efficacy, still needs more exploration
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Adding traditional treatments to maximize the benefits of patients.
In the research on the treatment of advanced refractory ovarian cancer, the reason why the autocrine PD-1 antibody CAR-T therapy is combined with apatinib is mainly due to the combination of autocrine PD-1 antibody CAR-T therapy and apatinib The multi-targeted anti-angiogenic drug represented by apatinib is one of the current treatment options for advanced ovarian cancer, and there are corresponding recommendations in the Chinese Clinical Oncology (CSCO) guidelines and the National Cancer Comprehensive Network (NCCN) guidelines
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In addition, researchers also want to compare traditional treatment methods with standard treatment methods to determine whether patients have more benefits
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In terms of mechanism, anti-angiogenesis therapy has the effect of improving the tumor microenvironment and can enhance the therapeutic effect of CAR-T on solid tumors
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The exploration of CAR-T therapy in solid tumors Professor Xu Qing pointed out that for all new treatment technologies or treatment products, the development of clinical research is to explore from the back-line treatment
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With the increase of evidence to verify the effectiveness of the back-line treatment, the direction of exploration will gradually move forward, in the hope that patients in the early stage will also be able to improve the efficacy
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CAR-T currently has satisfactory data in hematological malignancies, and the indications have been approved, and more indications have also entered the approval link of domestic and foreign drug regulatory authorities
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For the exploration of solid tumors, we can also learn from the experience of CAR-T in the clinical research of hematological tumors, for example, through the detection of peripheral blood tumor cells to guide CAR-T treatment
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Professor Xu Qing believes that this may be a direction for early intervention of solid tumors in the future
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Of course, the treatment of tumors cannot be won by fighting alone.
Both early and late interventions require multidisciplinary and multi-therapeutic methods to achieve the dual benefits of survival and quality of life for patients
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 Expert profile Professor Xu Qing, Doctor of Medicine, Second Military Medical University, chief physician, professor, and doctoral supervisor
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2002-2004, Postdoctoral and visiting scholar at H.
Lee.
Moffitt Cancer Center, University of South Florida, Florida, USA
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The main research areas are tumor cell signal transduction and tumor angiogenesis
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Director of the Oncology Department of our hospital, deputy director of the Department of Oncology, Tongji University School of Medicine
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He has been engaged in basic and clinical research work for a long time, and his related work has won the "Chinese People's Liberation Army Medical Achievement Award, Second Military Medical University Medical Achievement Award" and other awards
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Zeng Rongli once served third class in the army
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As the first author, he published SCI articles in the internationally renowned academic journals "Oncogene" and "DNA and Cell Biology" in the Nature series
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In recent years, he has published dozens of articles in the Zhonghua series and other medical professional journals, edited two monographs and participated in the editing of many
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He is currently funded by the Shanghai Pujiang Talents Program and other scientific research funds, and has participated in and presided over the National Natural Science Foundation, the Army Health Research Fund, the Shanghai Science and Technology Development Fund, the US NIH and other scientific research funds funded scientific research projects
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Concurrently serve as a special medical expert of the Shanghai European and American Alumni Association, a member of the American Association for Cancer Research (AACR), and a senior editorial board member of the "Anti-Cancer Trends" magazine
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Special reviewer for journals such as Journal of the Second Military Medical University, PLA Medical Journal (English Edition), and Chinese Journal of Cancer Biotherapy
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References: [1]αPD-1-mesoCAR-T cells partially inhibit the growth of advanced/refractory ovarian cancer in a patient along with daily apatinib.
JITC,2021,9(2):e001162.
doi:10.
1136/[2] Chinese Medical Doctor Association Multidisciplinary Cancer Diagnosis and Treatment Committee.
Guidelines for the Clinical Diagnosis and Treatment of Malignant Pleural Mesothelioma in China (2021 Edition)[J].
Chinese Journal of Oncology,2021,43(4):383-394.
DOI:10.
3760/cma.
j.
cn112152-20210313-00225.