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The 24th National Conference on Clinical Oncology and the 2021 CSCO Annual Conference will be held on September 25-29, 2021.
The theme of this conference is "Focus on Innovative Research, Leading the Original Future"
.
The conference continues to adhere to the fundamental purpose of CSCO, adopts new forms to actively carry out academic exchange activities in special periods, promotes academic exchanges and scientific and technological cooperation in the field of clinical oncology in China, encourages support for clinical research and innovation, and advocates multidisciplinary standardized comprehensive treatment based on Precision oncology actively promotes the development of the discipline
.
At this CSCO conference, Professor Liang Aibin from Tongji Hospital Affiliated to Tongji University gave a theme report on "Chimeric Antigen Receptor T Cell (CAR-T) Immunotherapy Treatment".
Yimaitong organized the main contents as follows
.
The overall goal of the CAR-T full-process management system In recent years, the National Health Commission has successively issued cell therapy industry policies, emphasizing the importance of CAR-T full-process management
.
Professor Liang Aibin said that although CAR-T is still effective in treating relapsed and refractory tumors in the blood system, the management of side effects cannot be ignored
.
Professor Liang Aibin emphasized that the overall goal of CAR-T treatment system management is to prevent the occurrence of potentially life-threatening toxic and side effects while maintaining the maximum efficacy of CAR-T treatment
.
CAR-T full-process management involves multiple links.
Professor Liang Aibin then introduced the CAR-T treatment process, including disease diagnosis, patient enrollment, informed consent, data collection, cell collection, CAR-T production, hospital admission, clinical risk control, patient follow-up and so on
.
The overall management of CAR-T treatment involves multiple links, and the management of each link needs to be fully evaluated and standardized
.
The risk assessment for patients to assess CAR-T treatment is more critical, which involves the assessment of patient baseline data and the physician's preliminary judgment on indications and prognosis of CAR-T treatment
.
The baseline examination of the patient includes the collection of medical history and previous comorbidities to assess the patient’s tumor location, tumor burden, and viral infection.
At the same time, it is also necessary to confirm the expression and mutation of CAR-T targets through tests such as flow cytometry and gene sequencing.
Situation
.
Different diseases have different toxic responses to CAR-T treatment
.
The results of the research carried out by Professor Liang Aibin’s team show that compared with non-Hodgkin’s lymphoma (NHL), the incidence of cytokine release syndrome (CRS) in patients with acute lymphoblastic leukemia (ALL) after CAR-T treatment is higher, but Patients with NHL are more likely to develop hypoimmunoglobulinemia
.
In addition, patients with larger tumor burdens have more obvious side effects after CAR-T treatment
.
Professor Liang Aibin said that hepatitis B virus activation will occur during CAR-T treatment in about 20% of patients in China, and management needs to be paid attention to
.
Professor Liang Aibin said that after evaluating the patients' indications for CAR-T treatment, it is necessary to detect the target expression and mutations before CAR-T treatment
.
At present, CD19 is the main target of CAR-T therapy.
If patients have CD19 point mutations or fragment deletions, CAR-T therapy can fail
.
In addition, if antigen escape occurs, the second infusion of the same target CAR-T will be invalid.
Therefore, the detection of gene mutations such as TP53 and STAG2 can help determine the prognosis of CAR-T treatment
.
The choice of pretreatment regimen Pretreatment chemotherapy can help reduce tumor burden and improve the efficacy of CAR-T treatment
.
Currently commonly used pretreatment chemotherapy regimens include cyclophosphamide monotherapy, fludarabine combined with cyclophosphamide, bendamustine combined with fludarabine and so on
.
Relevant studies have shown that the multi-drug combination pretreatment program may better reduce the tumor burden, but it may also bring stronger toxic and side effects
.
Comparison of different pretreatment programs shows that the pretreatment program of bendamustine combined with fludarabine can achieve a higher CAR-T treatment remission rate
.
Professor Liang Aibin said that the curative effect and side effects should be comprehensively measured, and the most suitable pretreatment plan for the patient should be selected
.
The existing CAR-T therapy for cell therapy covers a variety of targets and costimulatory molecules
.
Regarding the advantages and disadvantages of the two costimulatory molecules, CD28 and 4-1BB, Professor Liang Aibin said that CD28 produces a faster killing response than 4-1BB, but the duration of relief is shorter, while 4-1BB produces a slower killing response, but Relief can last a long time
.
In general, the comparison of clinical data based on the current characteristics of the main CAR-T therapy shows that the safety of CAR-T based on the 4-1BB costimulation domain may be better
.
Professor Liang Aibin then introduced the effects of CAR-T characteristics and infusion dose on the efficacy and toxicity
.
CAR-T cell populations with characteristics similar to myeloid cells are associated with severe immune effector cell-associated neurotoxicity syndrome (ICNAS), with depleted CD8 and CD4 T cells in the infusion products of patients with partial remission (PR)/disease progression (PD) Significantly enriched, and memory CD8 T cells were significantly enriched in the infusion products of patients with complete remission (CR)
.
In addition, increasing the infusion dose can increase the efficacy of NHL patients with high tumor burden, but for high-risk patients with CRS, the infusion dose needs to be reduced, and for leukemia patients, medium and low-dose infusions should be used
.
Toxicity Management Professor Liang Aibin said that the assessment and treatment of acute toxicity during CAR-T treatment is very important
.
At present, each center has gradually enriched the experience in the treatment of acute toxicity of CAR-T, including the treatment of CRS and ICANS
.
However, the treatment of chronic toxicity during CAR-T treatment, such as persistent thrombocytopenia or leukopenia, infection, hypoimmunoglobulinemia, and hepatitis B virus activation still need to be paid more attention
.
In addition, the excessive proliferation of CAR-T cells and the occurrence of second tumors are also the content that clinicians need to pay attention to
.
Professor Liang Aibin emphasized that only by strengthening the standardized management of side effects can the overall curative effect be improved
.
Concomitant detection refers to the detection of CAR-T cell expansion and cytokine levels in peripheral blood by RT-PCR, flow cytometry and other methods during CAR-T treatment
.
Concomitant testing can help predict the effect of treatment, assess the risk of recurrence, help formulate rescue treatment plans, and avoid blind treatment, which has important clinical value
.
CAR-T cells are immunogenic in anti-tumor therapy, and various monitoring, mitigation, and management methods can help reduce the risk of anti-CAR immunity
.
In addition, CRS is a common side effect in CAR-T therapy, and the severity of CRS can be determined through cytokine monitoring
.
Professor Liang Aibin then introduced the role of ctDNA detection and single-cell sequencing technology in CAR-T treatment monitoring: the change of ctDNA within one week of CAR-T treatment can predict the treatment effect early; single-cell sequencing can obtain T cells from CAR-T treated patients Distribution and detection of memory CD8+ T cells are the key to long-term survival of patients
.
The realization of CAR-T full-process management faces many challenges.
Professor Liang Aibin concluded that: Achieving CAR-T full-process management requires the cooperation of hospitals, patients, medical teams, pharmaceutical companies and other parties
.
Due to the current lack of multidisciplinary cooperation support, lack of treatment experience, and high treatment risks, CAR-T therapy still faces many challenges
.
It is hoped that by strengthening communication with patients, patients can fully understand the principles and risks and benefits of CAR-T treatment; strengthen cooperation with pharmaceutical companies and support product optimization through enriched clinical data; strengthen cooperation with various clinical departments and enrich team expertise , To accelerate the early realization of the entire management of CAR-T treatment
.
Professor Liang Aibin, doctoral supervisor, director of the Hematology Oncology Center, vice president of Shanghai Tongji Hospital, member of the Hematology Branch of the Chinese Medical Association, member of the National Standing Committee of the Chinese Medical Association, chairman designate of the Shanghai Society of Hematology, deputy director of the Shanghai Society of Immunology, deputy director of the Hematology Committee of the Shanghai Society of Immunology Committee members stamp "read the original text", we will make progress together
The theme of this conference is "Focus on Innovative Research, Leading the Original Future"
.
The conference continues to adhere to the fundamental purpose of CSCO, adopts new forms to actively carry out academic exchange activities in special periods, promotes academic exchanges and scientific and technological cooperation in the field of clinical oncology in China, encourages support for clinical research and innovation, and advocates multidisciplinary standardized comprehensive treatment based on Precision oncology actively promotes the development of the discipline
.
At this CSCO conference, Professor Liang Aibin from Tongji Hospital Affiliated to Tongji University gave a theme report on "Chimeric Antigen Receptor T Cell (CAR-T) Immunotherapy Treatment".
Yimaitong organized the main contents as follows
.
The overall goal of the CAR-T full-process management system In recent years, the National Health Commission has successively issued cell therapy industry policies, emphasizing the importance of CAR-T full-process management
.
Professor Liang Aibin said that although CAR-T is still effective in treating relapsed and refractory tumors in the blood system, the management of side effects cannot be ignored
.
Professor Liang Aibin emphasized that the overall goal of CAR-T treatment system management is to prevent the occurrence of potentially life-threatening toxic and side effects while maintaining the maximum efficacy of CAR-T treatment
.
CAR-T full-process management involves multiple links.
Professor Liang Aibin then introduced the CAR-T treatment process, including disease diagnosis, patient enrollment, informed consent, data collection, cell collection, CAR-T production, hospital admission, clinical risk control, patient follow-up and so on
.
The overall management of CAR-T treatment involves multiple links, and the management of each link needs to be fully evaluated and standardized
.
The risk assessment for patients to assess CAR-T treatment is more critical, which involves the assessment of patient baseline data and the physician's preliminary judgment on indications and prognosis of CAR-T treatment
.
The baseline examination of the patient includes the collection of medical history and previous comorbidities to assess the patient’s tumor location, tumor burden, and viral infection.
At the same time, it is also necessary to confirm the expression and mutation of CAR-T targets through tests such as flow cytometry and gene sequencing.
Situation
.
Different diseases have different toxic responses to CAR-T treatment
.
The results of the research carried out by Professor Liang Aibin’s team show that compared with non-Hodgkin’s lymphoma (NHL), the incidence of cytokine release syndrome (CRS) in patients with acute lymphoblastic leukemia (ALL) after CAR-T treatment is higher, but Patients with NHL are more likely to develop hypoimmunoglobulinemia
.
In addition, patients with larger tumor burdens have more obvious side effects after CAR-T treatment
.
Professor Liang Aibin said that hepatitis B virus activation will occur during CAR-T treatment in about 20% of patients in China, and management needs to be paid attention to
.
Professor Liang Aibin said that after evaluating the patients' indications for CAR-T treatment, it is necessary to detect the target expression and mutations before CAR-T treatment
.
At present, CD19 is the main target of CAR-T therapy.
If patients have CD19 point mutations or fragment deletions, CAR-T therapy can fail
.
In addition, if antigen escape occurs, the second infusion of the same target CAR-T will be invalid.
Therefore, the detection of gene mutations such as TP53 and STAG2 can help determine the prognosis of CAR-T treatment
.
The choice of pretreatment regimen Pretreatment chemotherapy can help reduce tumor burden and improve the efficacy of CAR-T treatment
.
Currently commonly used pretreatment chemotherapy regimens include cyclophosphamide monotherapy, fludarabine combined with cyclophosphamide, bendamustine combined with fludarabine and so on
.
Relevant studies have shown that the multi-drug combination pretreatment program may better reduce the tumor burden, but it may also bring stronger toxic and side effects
.
Comparison of different pretreatment programs shows that the pretreatment program of bendamustine combined with fludarabine can achieve a higher CAR-T treatment remission rate
.
Professor Liang Aibin said that the curative effect and side effects should be comprehensively measured, and the most suitable pretreatment plan for the patient should be selected
.
The existing CAR-T therapy for cell therapy covers a variety of targets and costimulatory molecules
.
Regarding the advantages and disadvantages of the two costimulatory molecules, CD28 and 4-1BB, Professor Liang Aibin said that CD28 produces a faster killing response than 4-1BB, but the duration of relief is shorter, while 4-1BB produces a slower killing response, but Relief can last a long time
.
In general, the comparison of clinical data based on the current characteristics of the main CAR-T therapy shows that the safety of CAR-T based on the 4-1BB costimulation domain may be better
.
Professor Liang Aibin then introduced the effects of CAR-T characteristics and infusion dose on the efficacy and toxicity
.
CAR-T cell populations with characteristics similar to myeloid cells are associated with severe immune effector cell-associated neurotoxicity syndrome (ICNAS), with depleted CD8 and CD4 T cells in the infusion products of patients with partial remission (PR)/disease progression (PD) Significantly enriched, and memory CD8 T cells were significantly enriched in the infusion products of patients with complete remission (CR)
.
In addition, increasing the infusion dose can increase the efficacy of NHL patients with high tumor burden, but for high-risk patients with CRS, the infusion dose needs to be reduced, and for leukemia patients, medium and low-dose infusions should be used
.
Toxicity Management Professor Liang Aibin said that the assessment and treatment of acute toxicity during CAR-T treatment is very important
.
At present, each center has gradually enriched the experience in the treatment of acute toxicity of CAR-T, including the treatment of CRS and ICANS
.
However, the treatment of chronic toxicity during CAR-T treatment, such as persistent thrombocytopenia or leukopenia, infection, hypoimmunoglobulinemia, and hepatitis B virus activation still need to be paid more attention
.
In addition, the excessive proliferation of CAR-T cells and the occurrence of second tumors are also the content that clinicians need to pay attention to
.
Professor Liang Aibin emphasized that only by strengthening the standardized management of side effects can the overall curative effect be improved
.
Concomitant detection refers to the detection of CAR-T cell expansion and cytokine levels in peripheral blood by RT-PCR, flow cytometry and other methods during CAR-T treatment
.
Concomitant testing can help predict the effect of treatment, assess the risk of recurrence, help formulate rescue treatment plans, and avoid blind treatment, which has important clinical value
.
CAR-T cells are immunogenic in anti-tumor therapy, and various monitoring, mitigation, and management methods can help reduce the risk of anti-CAR immunity
.
In addition, CRS is a common side effect in CAR-T therapy, and the severity of CRS can be determined through cytokine monitoring
.
Professor Liang Aibin then introduced the role of ctDNA detection and single-cell sequencing technology in CAR-T treatment monitoring: the change of ctDNA within one week of CAR-T treatment can predict the treatment effect early; single-cell sequencing can obtain T cells from CAR-T treated patients Distribution and detection of memory CD8+ T cells are the key to long-term survival of patients
.
The realization of CAR-T full-process management faces many challenges.
Professor Liang Aibin concluded that: Achieving CAR-T full-process management requires the cooperation of hospitals, patients, medical teams, pharmaceutical companies and other parties
.
Due to the current lack of multidisciplinary cooperation support, lack of treatment experience, and high treatment risks, CAR-T therapy still faces many challenges
.
It is hoped that by strengthening communication with patients, patients can fully understand the principles and risks and benefits of CAR-T treatment; strengthen cooperation with pharmaceutical companies and support product optimization through enriched clinical data; strengthen cooperation with various clinical departments and enrich team expertise , To accelerate the early realization of the entire management of CAR-T treatment
.
Professor Liang Aibin, doctoral supervisor, director of the Hematology Oncology Center, vice president of Shanghai Tongji Hospital, member of the Hematology Branch of the Chinese Medical Association, member of the National Standing Committee of the Chinese Medical Association, chairman designate of the Shanghai Society of Hematology, deputy director of the Shanghai Society of Immunology, deputy director of the Hematology Committee of the Shanghai Society of Immunology Committee members stamp "read the original text", we will make progress together
