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The introduction of relapsed and refractory Hodgkin’s lymphoma does not meet the needs and CD30 targeted therapy.
Hodgkin's lymphoma (HL) is a curable tumor of the blood system.
About 80% of newly diagnosed HL patients can be cured by chemotherapy, radiotherapy or combination therapy [1].
However, what is unsatisfactory is that as many as 20% of patients have primary refractory HL, and about 20% of HL patients relapse after first-line treatment [2], especially in advanced patients, the recurrence rate is 30% to 40% [3].
For these patients with relapsed or refractory HL, 50% of patients can obtain long-term remission after standard treatment, namely salvage chemotherapy followed by autologous stem cell transplantation (auto-SCT) [4], while 50% of patients relapse after auto-SCT , The prognosis is poor, the median survival time after auto-SCT failure is 25 months [2, 5]; especially for patients who relapse or progress within 1 year after auto-SCT (approximately 70 patients who relapse after auto-SCT) %[6]), the prognosis is extremely poor, and the median survival time is about 1.
2 years [4].
It can be seen that the treatment needs of HL patients, especially relapsed/refractory patients, are not met, and more effective and safe treatment drugs and programs are still needed.
In recent years, many new HL treatment drugs have been launched in China, bringing more choices and hopes to HL patients.
Among them, the antibody-conjugated drug (ADC) Vebutuximab (BV) that targets CD30 has been long-awaited, and was finally approved by the China National Medical Products Administration for the treatment of CD30-positive patients in May 2020.
Adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL) and relapsed or refractory classic HL (cHL).
To understand BV, we must start with understanding its target CD30, as well as the disease to be treated and its mechanism of action.
CD30: Opening the New World of HL Therapy 01 The discovery of CD30, the target of treatment, as early as 1982, researchers discovered an antigen recognized by Ki-1, a monoclonal antibody that specifically binds to HL Reed-Sternberg cells, namely "Ki-1" "This is also the original name of CD30.
Later, CD30 (Ki-1) was identified as a 120 kDa transmembrane glycoprotein receptor belonging to the tumor necrosis factor receptor (TNFR) superfamily, namely "Tumor Necrosis Factor Receptor Superfamily Member 8 (TNFRSF8)" [ 7, 8].
02CD30's biological function CD30 exerts its physiological effects through a series of different signal pathways.
The stimulation of CD30 molecules can induce receptor trimerization and signal transduction, which in turn activates the nuclear factor-κB (NFκB) pathway.
At the same time, CD30 is also involved in the mitogen-activated protein kinase (MAPK) pathway (including ERK1 and ERK2), which plays an anti-apoptotic and pro-survival role in tumor cells.
In addition, there seems to be a positive feedback loop between the MAPK/ERK pathway and NFκB, which not only contributes to cell survival, but also up-regulates CD30 expression (Figure 1) [8].
This suggests that the expression of CD30 in tumor cells may have proliferation and anti-apoptotic effects.
Figure 1 CD30-related signal transduction pathways In addition, based on different cell environments, CD30 signal transduction can play very different roles-apoptosis and cell proliferation (Figure 2), that is, pleiotropic effects [8, 9].
Figure 2 The structure of CD30 and the schematic diagram of signal transduction mediated by the recruitment of tumor necrosis factor receptor-related factors (TRAF) CD30 is expressed in a variety of lymphomas, especially in cHL and ALCL, but is highly expressed in normal tissues [8 ,9].
This means that it is an ideal target for the treatment of CD30+ lymphoma.
When will the development of CD30 target drugs take a turn? Although CD30 has been discovered for more than a hundred years, it has not been long for CD30 target drugs to be used in clinical practice.
Since the 1990s, some researchers have explored CD30 antibodies, while others have been working on CD30 antibody-conjugated drugs.
After several rounds of "tests", very few eventually entered the clinic.
For example, the first-generation anti-CD30 humanized monoclonal antibodies (SGN-30, MDX-060, HeFi-1) and the second-generation anti-CD30 humanized monoclonal antibodies (XmAb2513, MDX-1401) have entered clinical trials, but the results None of them are ideal [7, 9].
Anti-CD30 antibody conjugates-immunotoxins, bispecific antibodies, and radioimmunoconjugates have been studied successively.
However, studies have shown that the clinical efficacy of anti-CD30 immunotoxin conjugate BerH2-SO6 is short (6-10 weeks), and multiple bispecific antibodies such as H22xKi-4 are well tolerated but have limited efficacy.
Anti-CD30 radioimmunoassays are occasional The high incidence of blood toxicity of conjugate (131 I-Ki-4) limits its use [7, 9].
In the 21st century, the advent of Vebutuximab (BV), an ADC targeting CD30, reignited the hope of CD30 targeted therapy.
How does BV affect CD30+ lymphoma? CD30+ lymphomas include cHL, ALCL, NK/T-cell lymphoma, angioimmunoblastic T-cell lymphoma, adult T-cell leukemia/lymphoma, diffuse large B-cell lymphoma, etc.
that express positive cell surface antigen CD30.
The general term for lymphoma subtypes [10].
Among them, cHL and ALCL showed high expression of CD30 [8].
Verbutuximab is an antibody-conjugated drug formed by linking the CD30-targeting monoclonal antibody cAC10 and the anti-microtubule drug monomethyl auristatin E (MMAE) via a dipeptide linker, which remains stable in the blood .
Vebutuximab mainly targets CD30+ tumor cells to release MMAE, inhibit microtubule polymerization, arrest G2/M phase and cause apoptosis, and cause bystander effect to kill neighboring cells to achieve a precise anti-tumor effect (Figure 3) [7,9].
Figure 3 Schematic diagram of the structure and mechanism of action of Vibutuximab.
In 2003, preliminary data from BV evaluation showed that it had highly effective and selective anti-tumor activity.
Subsequent clinical trials confirmed that BV has excellent efficacy and good safety in the treatment of relapsed or refractory sALCL and cHL in CD30+ lymphoma.
As the world’s first and currently the only ADC targeting CD30, the advent of BV has opened a new era in the treatment of CD30+ lymphoma, and has also added new options for patients with CD30+ lymphoma.
We look forward to further clinical data that it will bring ! References[1] Majhail NS, Weisdorf DJ, Defor TE, et al.
Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin's lymphoma[J].
Biol Blood Marrow Transplant.
2006 Oct;12(10): 1065-72.
[2] Moskowitz AJ, Perales M, Kewalramani T, et al.
Outcomes for patients who fail high dose chemoradiotherapy and autologous stem cell rescue for relapsed and primary refractory Hodgkin lymphoma[J].
Br J Haematol.
2009 Jul; 146(2):158-63.
[3] Ramchandren R.
Advances in the treatment of relapsed or refractory Hodgkin's lymphoma[J].
Oncologist.
2012;17(3):367-76.
[4] Younes A, Gopal AK , Smith SE, et al.
Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma[J].
J Clin Oncol. The content of the information published by this site does not mean that it agrees with its description and opinions, but only provides more information.
If copyright issues are involved, please contact us, and we will deal with it as soon as possible.
Only for medical and health professionals to understand the information.
Such information cannot replace professional medical guidance in any way, nor should it be regarded as diagnosis and treatment advice.
If such information is used for purposes other than understanding the information, this site and the author shall not bear related responsibilities.
VV-MEDMAT-423973/31/2021 RECOMMEND Recommended Reading 1.
An article to understand the key information of peripheral T-cell lymphoma 2.
CD30+ Lymphoma series | CD30 struck by wind and waves! 3.
Decoding the diagnosis of CD30+ lymphoma, Get essential knowledge points of clinical and pathology 4.
After riding the wind and breaking the waves, Verbituximab is on the stage | CD30+ Lymphoma series 5.
You do not know ADC drugs for the treatment of hematological tumors, you It's out! (Easter eggs at the end of the article) 6.
Who is responsible for lymphoma treatment? CD30 memorabilia at a glance | September 15 World Lymphoma Day 7.
When encountering elderly Hodgkin’s lymphoma, it is important to understand these questions.
8.
For you, is this patient a lymphoma? The "pretender" that is not easy to distinguish 9.
More reference value! How effective is Verbutuximab in the real world in Asia? 10.
From the biomarkers, look at the treatment progress of each subtype of peripheral T-cell lymphoma.
11.
The NCCN guidelines have been updated! Interpretation of peripheral T-cell lymphoma of the 2021.
V1 version, click here to "read the original text", and we will make progress together
Hodgkin's lymphoma (HL) is a curable tumor of the blood system.
About 80% of newly diagnosed HL patients can be cured by chemotherapy, radiotherapy or combination therapy [1].
However, what is unsatisfactory is that as many as 20% of patients have primary refractory HL, and about 20% of HL patients relapse after first-line treatment [2], especially in advanced patients, the recurrence rate is 30% to 40% [3].
For these patients with relapsed or refractory HL, 50% of patients can obtain long-term remission after standard treatment, namely salvage chemotherapy followed by autologous stem cell transplantation (auto-SCT) [4], while 50% of patients relapse after auto-SCT , The prognosis is poor, the median survival time after auto-SCT failure is 25 months [2, 5]; especially for patients who relapse or progress within 1 year after auto-SCT (approximately 70 patients who relapse after auto-SCT) %[6]), the prognosis is extremely poor, and the median survival time is about 1.
2 years [4].
It can be seen that the treatment needs of HL patients, especially relapsed/refractory patients, are not met, and more effective and safe treatment drugs and programs are still needed.
In recent years, many new HL treatment drugs have been launched in China, bringing more choices and hopes to HL patients.
Among them, the antibody-conjugated drug (ADC) Vebutuximab (BV) that targets CD30 has been long-awaited, and was finally approved by the China National Medical Products Administration for the treatment of CD30-positive patients in May 2020.
Adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL) and relapsed or refractory classic HL (cHL).
To understand BV, we must start with understanding its target CD30, as well as the disease to be treated and its mechanism of action.
CD30: Opening the New World of HL Therapy 01 The discovery of CD30, the target of treatment, as early as 1982, researchers discovered an antigen recognized by Ki-1, a monoclonal antibody that specifically binds to HL Reed-Sternberg cells, namely "Ki-1" "This is also the original name of CD30.
Later, CD30 (Ki-1) was identified as a 120 kDa transmembrane glycoprotein receptor belonging to the tumor necrosis factor receptor (TNFR) superfamily, namely "Tumor Necrosis Factor Receptor Superfamily Member 8 (TNFRSF8)" [ 7, 8].
02CD30's biological function CD30 exerts its physiological effects through a series of different signal pathways.
The stimulation of CD30 molecules can induce receptor trimerization and signal transduction, which in turn activates the nuclear factor-κB (NFκB) pathway.
At the same time, CD30 is also involved in the mitogen-activated protein kinase (MAPK) pathway (including ERK1 and ERK2), which plays an anti-apoptotic and pro-survival role in tumor cells.
In addition, there seems to be a positive feedback loop between the MAPK/ERK pathway and NFκB, which not only contributes to cell survival, but also up-regulates CD30 expression (Figure 1) [8].
This suggests that the expression of CD30 in tumor cells may have proliferation and anti-apoptotic effects.
Figure 1 CD30-related signal transduction pathways In addition, based on different cell environments, CD30 signal transduction can play very different roles-apoptosis and cell proliferation (Figure 2), that is, pleiotropic effects [8, 9].
Figure 2 The structure of CD30 and the schematic diagram of signal transduction mediated by the recruitment of tumor necrosis factor receptor-related factors (TRAF) CD30 is expressed in a variety of lymphomas, especially in cHL and ALCL, but is highly expressed in normal tissues [8 ,9].
This means that it is an ideal target for the treatment of CD30+ lymphoma.
When will the development of CD30 target drugs take a turn? Although CD30 has been discovered for more than a hundred years, it has not been long for CD30 target drugs to be used in clinical practice.
Since the 1990s, some researchers have explored CD30 antibodies, while others have been working on CD30 antibody-conjugated drugs.
After several rounds of "tests", very few eventually entered the clinic.
For example, the first-generation anti-CD30 humanized monoclonal antibodies (SGN-30, MDX-060, HeFi-1) and the second-generation anti-CD30 humanized monoclonal antibodies (XmAb2513, MDX-1401) have entered clinical trials, but the results None of them are ideal [7, 9].
Anti-CD30 antibody conjugates-immunotoxins, bispecific antibodies, and radioimmunoconjugates have been studied successively.
However, studies have shown that the clinical efficacy of anti-CD30 immunotoxin conjugate BerH2-SO6 is short (6-10 weeks), and multiple bispecific antibodies such as H22xKi-4 are well tolerated but have limited efficacy.
Anti-CD30 radioimmunoassays are occasional The high incidence of blood toxicity of conjugate (131 I-Ki-4) limits its use [7, 9].
In the 21st century, the advent of Vebutuximab (BV), an ADC targeting CD30, reignited the hope of CD30 targeted therapy.
How does BV affect CD30+ lymphoma? CD30+ lymphomas include cHL, ALCL, NK/T-cell lymphoma, angioimmunoblastic T-cell lymphoma, adult T-cell leukemia/lymphoma, diffuse large B-cell lymphoma, etc.
that express positive cell surface antigen CD30.
The general term for lymphoma subtypes [10].
Among them, cHL and ALCL showed high expression of CD30 [8].
Verbutuximab is an antibody-conjugated drug formed by linking the CD30-targeting monoclonal antibody cAC10 and the anti-microtubule drug monomethyl auristatin E (MMAE) via a dipeptide linker, which remains stable in the blood .
Vebutuximab mainly targets CD30+ tumor cells to release MMAE, inhibit microtubule polymerization, arrest G2/M phase and cause apoptosis, and cause bystander effect to kill neighboring cells to achieve a precise anti-tumor effect (Figure 3) [7,9].
Figure 3 Schematic diagram of the structure and mechanism of action of Vibutuximab.
In 2003, preliminary data from BV evaluation showed that it had highly effective and selective anti-tumor activity.
Subsequent clinical trials confirmed that BV has excellent efficacy and good safety in the treatment of relapsed or refractory sALCL and cHL in CD30+ lymphoma.
As the world’s first and currently the only ADC targeting CD30, the advent of BV has opened a new era in the treatment of CD30+ lymphoma, and has also added new options for patients with CD30+ lymphoma.
We look forward to further clinical data that it will bring ! References[1] Majhail NS, Weisdorf DJ, Defor TE, et al.
Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin's lymphoma[J].
Biol Blood Marrow Transplant.
2006 Oct;12(10): 1065-72.
[2] Moskowitz AJ, Perales M, Kewalramani T, et al.
Outcomes for patients who fail high dose chemoradiotherapy and autologous stem cell rescue for relapsed and primary refractory Hodgkin lymphoma[J].
Br J Haematol.
2009 Jul; 146(2):158-63.
[3] Ramchandren R.
Advances in the treatment of relapsed or refractory Hodgkin's lymphoma[J].
Oncologist.
2012;17(3):367-76.
[4] Younes A, Gopal AK , Smith SE, et al.
Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma[J].
J Clin Oncol. The content of the information published by this site does not mean that it agrees with its description and opinions, but only provides more information.
If copyright issues are involved, please contact us, and we will deal with it as soon as possible.
Only for medical and health professionals to understand the information.
Such information cannot replace professional medical guidance in any way, nor should it be regarded as diagnosis and treatment advice.
If such information is used for purposes other than understanding the information, this site and the author shall not bear related responsibilities.
VV-MEDMAT-423973/31/2021 RECOMMEND Recommended Reading 1.
An article to understand the key information of peripheral T-cell lymphoma 2.
CD30+ Lymphoma series | CD30 struck by wind and waves! 3.
Decoding the diagnosis of CD30+ lymphoma, Get essential knowledge points of clinical and pathology 4.
After riding the wind and breaking the waves, Verbituximab is on the stage | CD30+ Lymphoma series 5.
You do not know ADC drugs for the treatment of hematological tumors, you It's out! (Easter eggs at the end of the article) 6.
Who is responsible for lymphoma treatment? CD30 memorabilia at a glance | September 15 World Lymphoma Day 7.
When encountering elderly Hodgkin’s lymphoma, it is important to understand these questions.
8.
For you, is this patient a lymphoma? The "pretender" that is not easy to distinguish 9.
More reference value! How effective is Verbutuximab in the real world in Asia? 10.
From the biomarkers, look at the treatment progress of each subtype of peripheral T-cell lymphoma.
11.
The NCCN guidelines have been updated! Interpretation of peripheral T-cell lymphoma of the 2021.
V1 version, click here to "read the original text", and we will make progress together
