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Objective @#To develop a CD30-targeted CAR-T cell drug based on the multi-chain chimeric antigen re- ceptor T cells (CAR-T) of the bridging protein DAP12 , and to study the in vitro and in vivo preclinical efficacy of CD30 CAR-T on Hodgkin lymphoma tumor cells .@*Methods @#Through gene synthesis and molecular cloning tech- niques , a CAR plasmid targeting CD30 was designed and constructed , and the obtained lentivirus was packaged . The T cells were transfected with the lentivirus , where the multi-chain CAR-T targeting CD30 was the CD30 - KIRS2/Dap12-BB group , the single-chain second-generation CAR-T was the CD30-41BBζgroup , and the T cells without virus infection were the NTD group . The positive rate of CAR was detected by flow cytometry , the cytotoxic- ity of the cells was detected by lactate dehydrogenase (LDH) release assay , the secretion level of the cytokine in- terferon γ(IFN-γ) was detected by enzyme-linked immunosorbent assay ( ELISA) , and the antitumor activity of CD30 CAR-T in mice was further detected by a mouse xenograft tumor model . @*Results @#A comparison was made between the multi-chain CAR-T targeting CD30 and the single-chain second-generation CAR-T. It was found that the antitumor effect of the multi-chain CAR-T was similar to that of the single-chain CAR-T. However , it was worth noting that the IFN-γsecretion level of the multi-chain CAR-T was higher (P < 0 . 001) . More importantly , in the mouse tumor model experiment , the multi-chain CAR-T achieved complete tumor regression . @*Conclusion @#The multi-chain CAR-T targeting CD30 is superior to the traditional single-chain CAR-T in terms of antitumor activity .
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Objective:To develop the anti-CD30 monoclonal antibody 64Cu-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD30 and visualize CD30 expression in lymphoma non-invasively. Methods:The CD30 expression levels of 5 cell lines (Karpas299, Raji, Daudi, Ramos, and U266) were assessed by Western blot. Cell lines with high and low CD30 expression were selected for flow cytometry to evaluate the specific binding affinity of anti-CD30 monoclonal antibody. Thirteen NSG mice were used to established CD30 positive and negative subcutaneous xenograft models. 64Cu-NOTA-CD30 was obtained and 64Cu-NOTA-immunoglobulin (Ig)G was used as the control. ImmunoPET imaging was performed 2, 24, and 48 h after the injection of 64Cu-NOTA-CD30 or 64Cu-NOTA-IgG. Finally, the biodistribution studies were conducted. Repeated-measures analysis of variance and Bonferroni test were conducted for comparison. Results:Karpas299 showed the highest CD30 expression, while Raji showed the lowest. Flow cytometry showed specific binding affinity of the anti-CD30 monoclonal antibody to the Karpas299 cell line. The radiochemical purities of the probes were both higher than 95%. In microPET, the 64Cu-NOTA-CD30 uptake of Karpas299 xenograft tumors increased over time, with (11.46±0.58), (17.60±1.16) and (19.46±0.99) percentage activity of injection dose per gram of tissue (%ID/g) at 2, 24 and 48 h respectively. The contrast to normal tissue was good at 48 h, with the tumor/heart (blood) ratio of 2.20±0.22. The uptake of 64Cu-NOTA-CD30 in Karpas299 tumor at 48 h after injection was significantly higher than that in Raji tumor ((6.10±1.03) %ID/g) and 64Cu-NOTA-IgG in Karpas299 tumor ((5.12±0.89) %ID/g; F=290.99, t values: 19.65 and 22.25, all P<0.001). The uptake of 64Cu-NOTA-CD30 and the control probe in the heart and liver decreased over time in all groups. Ex vivo biodistribution at 48 h was mainly consistent with the results of microPET in vivo. Conclusions:64Cu-NOTA-CD30 is able to visualize the expression level and distribution of CD30 non-invasively. It is promising to be applied for screening the beneficial groups and evaluating efficacy for CD30-targeted immunotherapy.
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Objective:To investigate clinicopathological features and prognosis of transformed mycosis fungoides (TMF) .Methods:A retrospective analysis was performed on clinicopathological data collected from 24 patients with TMF, as well as on flow cytometry results of 16 peripheral blood samples obtained from 11 of the 24 patients, who visited Hospital of Dermatology, Chinese Academy of Medical Sciences between 2014 and 2020.Results:Among the 24 patients, 11 were males and 13 were females. Their average age at diagnosis of TMF was 50.0 years (range: 18 - 77 years), and patients with early-stage TMF (9 cases) and tumor-stage TMF (15 cases) were aged 44.8 and 52.6 years on average, respectively. The average time interval from diagnosis of MF to large cell transformation was 3.7 years, and 8 patients were diagnosed with TMF at the initial visit. Histopathologically, large cells infiltrated in a diffuse pattern in 20 cases, as well as in a multifocal pattern in 4, and the proportion of large cells in 7 cases was greater than 75%. Immunohistochemically, 18 patients showed positive staining for CD30, and the proportion of CD30-positive large cells was greater than 75% in 9; negative staining for CD30 was observed in 6. Flow cytometry of 16 peripheral blood samples showed the presence of cell subsets expressing clonal T cell receptor (TCR) -vβ in 2 of 4 patients with early-stage TMF and 10 of 12 with tumor-stage TMF, and tumor cells with higher forward scatter than normal lymphocytes were detected in 16 samples. During the follow-up, among the patients with early-stage TMF, 3 progressed to tumor-stage TMF 3.3 years on average after large cell transformation, 1 progressed to erythrodermic MF in stage IIIA, and the other 4 still showed an indolent course; among the patients with tumor-stage TMF, 1 progressed to stage-IV TMF, and 5 died 3.3 (1.5 - 6) years after large cell transformation.Conclusion:Large cell transformation may occur in patients with MF in any stage, some patients have poor prognosis, so close follow-up is needed for patients with TMF.
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Objective To explore the application value of treatment-related markers PD-L1, PD-L2, CD30, CD23, BCL-2, BCL-6, MUM1 and GATA3 in the diagnosis and prognostic evaluation of primary mediastinal B-cell lymphoma(PMBL). Methods A retrospective study was conducted on 34 patients diagnosed with PMBL, and 31 patients with DLBCL-NOS which was not primary in the mediastinum were taken as control group. The expressions of 8 proteins were detected by IHC staining. Results The median percentages of tumor cells with PD-L1, PD-L2 and CD30 expression in PMBL group were 70% (30%, 90%), 25% (0, 70%) and 17.5% (0, 60%) respectively, which were significantly higher than those in the DLBCL-NOS group (P < 0.05). The positive rates of CD30 and CD23 in PMBL group were 61.76% (21/34) and 76.47% (26/34) respectively, significantly different with those in the DLBCL-NOS group (P=0.000). The survival curve of PMBL patients with CD30 or BCL-6 expression showed a trend of poor prognosis, despite the P value was > 0.05. Conclusion The high expression levels of PD-L1, PD-L2 and CD30 in PMBL are helpful to accurately identify more patients who may respond to immune or targeted therapy. Immunohistochemical staining of PD-L1, PD-L2, CD30 and CD23 is helpful for the differential diagnosis of PMBL and DLBCL-NOS. As candidate prognostic indicators of PMBL, CD30 and BCL-6 should be further studied in a larger number of samples.
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O linfoma anaplásico de células grandes associado a implante mamário (BIA-ALCL ) é uma entidade provisória com características morfológicas e imunofenotípicas indistinguíveis do linfoma anaplásico de células grandes (ALCL) ALK negativo. Ao contrário do ALCL, o BIA-ALCL surge principalmente em associação ao implante mamário. A confirmação diagnóstica do BIA-ALCL pode ser difícil e a associação de características morfológicas e patológicas com citometria de fluxo e imuno-histoquímica pode auxiliar no diagnóstico. O objetivo deste relatório é descrever um caso de BIA-ALCL no qual a análise citológica e imunofenotipológica utilizando citometria de fluxo sugeriu a presença de grandes células positivas para CD30 no líquido de derrame.
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a provisional entity with morphological and immunophenotypic characteristics indistinguishable from ALKnegative anaplastic large cell lymphoma (ALCL). Unlike ALCL, BIA-ALCL arises mainly in association with breast implantation. Diagnostic confirmation of BIA-ALCL can be difficult and associating morphological and pathological hallmarks with flow cytometry and immunohistochemistry can assist in the diagnosis. The objective of this report is to describe a case of BIA-ALCL in which cytological and immunophenotypological analysis using flow cytometry suggested the presence of large CD30-positive cells in the effusion fluid.
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Resumen Introducción: El linfoma anaplásico de células T grandes CD30+ es un linfoma primario cutáneo en el cual no hay evidencia de enfermedad sistémica; para su diagnóstico es necesario el estudio histopatológico. Objetivo: Presentar los casos diagnosticados en el Departamento de Dermatología del Hospital General "Dr. Manuel Gea González" con linfomas anaplásicos de células T grandes primarios cutáneos CD30+ durante un periodo de 24 años. Método: Estudio retrospectivo en el que realizó estadística descriptiva. Se recopiló información de sexo, edad, características clínicas, resultados de pruebas complementarias, tratamientos previos y actuales, reportes de los estudios histopatológicos y de inmunohistoquímica. Resultados: Entre 29 309 expedientes, se encontraron nueve casos (0.000034 %) con diagnóstico de linfoma anaplásico de células T CD30+. Se hizo la confirmación del diagnóstico histopatológico e inmunohistoquímico por dos dermatopatólogos certificados. La edad promedio fue de 61.2 años, hubo predominio del sexo femenino y de lesión papular o nodular y topografía variada como presentación clínica inicial. Conclusiones: El pronóstico del linfoma anaplásico de células T grandes CD30+ en la población estudiada fue dependiente del estadio clínico. El tratamiento en etapas tempranas tiene resultados favorables.
Abstract Introduction: CD30+ anaplastic large T cell lymphoma is a cutaneous primary lymphoma in which there is no evidence of systemic disease; histopathological study is required for its diagnosis. Objective: To present the cases diagnosed with primary cutaneous CD30+ anaplastic large T-cell lymphoma over a 24-year period in Hospital General "Dr. Manuel Gea González" Department of Dermatology. Method: Retrospective study. Descriptive statistics was carried out. Information was collected on gender, age, clinical characteristics, complementary test results, previous and current treatments, histopathological studies reports and immunohistochemistry test results. Results: Of 29 309 records, nine patients (0.000034%) with a diagnosis of CD30+ anaplastic T cell lymphoma were found. Histopathological and immunohistochemical diagnosis was confirmed by two certified dermatopathologists. Average age was 61.2 years, and there was a predominance of the female gender, with initial clinical presentation as a papular or nodular lesion and varied topography. Conclusions: The prognosis of CD30+ anaplastic large T cell lymphoma in the studied population was dependent on clinical stage. The treatment at early stages has favorable results.
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Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Skin Neoplasms/pathology , Lymphoma, Large-Cell, Anaplastic/pathology , Ki-1 Antigen/metabolism , Prognosis , Skin Neoplasms/diagnosis , Retrospective Studies , Lymphoma, Large-Cell, Anaplastic/diagnosis , Neoplasm StagingABSTRACT
Plasmablastic lymphoma (PBL) is a distinctly rare neoplasm believed to arise from post-germinal center, terminally differentiated, activated B cells before transformation to plasma cells; and predominantly affecting human immunodeficiency virus (HIV) infected or immunodeficient males. Here, we report a rare case of primary PBL of bone marrow in an immunocompetent male, the diagnosis of which is complicated by the overlapping morphology and immunophenotype with several large cell lymphomas and plasma cell neoplasms; and showing dramatic response to anti-CD30 monoclonal antibody based therapy. We discuss the immunohistochemistry based approach and the possible diagnostic pitfalls in such cases. The inclusion of markers of plasmablastic differentiation in the diagnostic panel of large cell lymphomas is essential to avoid misclassification of these rare lymphomas.
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Introduction@#Primary cutaneous anaplastic large cell lymphoma (PCALCL) is an uncommonly encountered subtype of cutaneous lymphoma under the classification of CD30-positive lymphoproliferative disorders which presents histologically as large atypical lymphocytes with pleomorphic and anaplastic cytology that localizes to the dermis. Although recurrent, PCALCL usually carries a good prognosis, with 5-year survival rates ranging from 85% to 95%.@*Case Summary@#We report a 73-year-old elderly male who consulted at our out-patient department with a 3-year and 6-month history of multifocal, gradually enlarging, erythematous nodules with dry, necrotic areas on the scalp, right auricular area, left axillary area, right forearm, and right thigh, accompanied by loss of appetite and nontender cervical, left axillary, and right inguinal lymphadenopathy. Previous skin punch biopsy and immunohistochemical stain done by the patient’s preceding dermatologist was signed out as “suggestive” of pseudolymphoma. However, management with intralesional corticosteroid injections provided no improvement. Skin punch biopsy done at our institution revealed ALK negative (-) anaplastic large cell lymphoma. Patient was then referred to an oncologist, however, the patient was lost to follow-up and succumbed to community acquired pneumonia.@*Conclusion@#This case highlights the importance of a thorough diagnostic assessment as recent studies indicate a poorer prognosis of ALK (-) cases, with overall 5-year survival rates consistently below 50%.
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Lymphoma , Lymphoma, Large-Cell, AnaplasticABSTRACT
Extranodal NK/T-cell lymphoma (ENKTCL) is a relatively rare group of highly aggressive non-Hodgkin′s lymphoma (NHL). The disease has rapid clinical progress, high degree of malignancy and poor prognosis. Traditional chemoradiotherapy regimens have not shown good efficacy. In recent years, the immunotherapy of tumors has developed rapidly. At present, it has shown strong therapeutic activity in the treatment of various solid tumors such as non-small cell lung cancer, prostate cancer, melanoma and kidney cancer. Multiple tumor immunotherapy drugs have been approved by the US Food and Drug Administration (FDA) for clinical use. This article reviews recent novel immunotherapeutic regimens of ENKTCL, hoping to change the treatment modality of this malignant disease.
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Objective: The expression of CD30 in peripheral lymphoma T cell lymphoma,unspecified (PTCL-U) was analyzed, and the correlations between CD30 and clinical survival and prognosis were studied. Methods: The clinical and pathological indicators of 56 patients with PTCL-U, who were newly treated in The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2017, were obtained. Among the 56 patients, the male to female ratio was 1.7∶1. The median age was 60 (16?76) years. The categorical variables were analyzed by the Chi-square test. Kaplan-Meier method was used for the survival analysis along with an assessment of the differences by Log-rank test. Logistic univariate analysis and Cox multivariate regression model analysis were used to analyze the indicators affecting survival. Results: The 3-year and 5-year overall survival (OS) rates of 56 patients were 42.2% and 20.4%, respectively, and the progression-free survival (PFS) rates were 32.1% and 17.8%, respectively. The median overall survival (median-OS, mOS) was 31 months, and the median progression-free survival (median-PFS, mPFS) was 11 months. The positive expression rate of CD30 in PTCL-U patients was 35.7%. The positive expression of CD30 was more common in advanced patients. The LDH level was increased, and the number of extra-nodal lesions was≥2 in the middle-high risk patients. Further, the initial treatment effects in the positive patients were not good (P<0.05). Among the 56 patients, CHOP regimen and GDPT regimen were adopted for chemotherapy, and the two regimens showed no statistically significant effects on OS and PFS (P>0.05). The survivals in the CD30 positive and negative groups were as follows: the 3 years-OS were 16.5% and 54.9%, respectively (P=0.001); and the 3-years PFS were 11.2% and 44.5%, respectively (P=0.016). The univariate analysis showed that advanced disease, CD30-positivity, IPI/aaIPI-high risk, and PIT-high risk (P>0.05) were adverse prognostic factors. The multivariate analysis showed that staging and PIT were correlated with survival. Conclusions: The expression of CD30 in PTCL-U was low, and the prognosis of the positive-expression group was poor. The positive expression was more associated with advanced disease, high level of LDH, and medium-high risk group. The positive group was more prone to extranodal involvement and the objective remission rate was lower. Staging, CD30, IPI/aaIPI, and PIT could affect the prognosis in these patients.
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Background: Triple-negative breast cancer (TNBC) lacks the benefits of receptor-targeted therapeutic strategies. The limitations in treatment options along with poor patients' outcome heighten the need for novel approaches. Due to recent concentration on the role of biomarkers in prognosis, treatment, and survival of various cancer subtypes, this study involves an investigation of CD4, CD8, and CD30 markers detected by immunohistochemistry in TNBCs and their association with clinicopathological and prognostic factors. Materials and Methods: Tissue samples of 85 hormone receptor- and human epidermal growth factor receptor-2-negative ductal breast carcinomas extracted from the archive of pathology department. Regarding CD4/CD8 ratio, the infiltrated T-lymphocytes were investigated. The tumoral tissue regions were also identified to be immunohistochemically assessed for the CD30 expression levels. Results: With an elevated CD4/CD8 ratio, a significant increase in lymph node involvement was observed (P < 0.05); in contrast, increased expression levels of CD8 were related to significant reduction of lymph node involvement. CD30 overexpression was found to be significantly associated with shortened overall survival (OS) and highly involvement of lymph nodes. Conclusion: Following the progression in stage and grade of tumor, CD4/CD8 ratio and CD30 expression levels are increased and are accompanied by adverse prognosis and poor OS, while CD8-enhanced expression carries a favorable prognostic impact as it improves OS status. Therefore, all these findings could be of interest in the field of target therapy.
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Lymphomatoid papulosis type E (LyP) is a recently described subtype of LyP characterized by an angioinvasive infiltrate of atypical lymphocytes expressing CD30. We present a case of type E LyP with extensive cutaneous necrosis in the histopathological evaluation which was misdiagnosed as an ulcerative form of bacterial skin infection. The remarkable cutaneous necrosis showed in our case might be related to the angiodestructive infiltrate that was present in this circumstance.
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Lymphomatoid papulosis type E (LyP) is a recently described subtype of LyP characterized by an angioinvasive infiltrate of atypical lymphocytes expressing CD30. We present a case of type E LyP with extensive cutaneous necrosis in the histopathological evaluation which was misdiagnosed as an ulcerative form of bacterial skin infection. The remarkable cutaneous necrosis showed in our case might be related to the angiodestructive infiltrate that was present in this circumstance.
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Lymphomatoid papulosis (LyP) is defined as a chronic, recurrent, self-healing papulonecrotic or papulonodular skin disease with histologic features suggestive of a (CD30-positive) malignant lymphoma. In up to 20% of patients, LyP are preceded by, associated with, or followed by another type of cutaneous or systemic lymphoma, generally mycosis fungoides (MF), primary cutaneous anaplastic large cell lymphoma (C-ALCL). In this case, we describe a case of MF that preceded and continued to coexist with LyP type C.(AU)
A papulose linfomatóide (LyP) é definida como uma doença cutânea papulonecrótica ou papulonodular crônica, recorrente, com características histológicas sugestivas de linfoma maligno (CD30-positivo). Em até 20% dos pacientes, o LyP é precedido por, associado ou seguido por outro tipo de linfoma cutâneo ou sistêmico, geralmente micose fungóide (MF), linfoma cutâneo primário de células grandes anaplásicas (C-ALCL). Neste caso, descrevemos um caso de MF que precedeu e continuou a coexistir com LyP tipo C. (AU)
Subject(s)
Humans , Female , Adult , Lymphoma , Lymphoma, Primary Cutaneous Anaplastic Large Cell , Lymphomatoid Papulosis , Mycosis Fungoides , T-LymphocytesABSTRACT
Objective To deepen the understanding of curative effect and adverse drug reaction of brentuximab vedotin in the treatment of Hodgkin's lymphoma.Methods One case of newly diagnosed Hodgkin's lymphoma who treated with brentuximab vedotin was collected.The clinical features,laboratory examination,treatment procedure,prognosis were analyzed,and the relevant literature was reviewed.Results The patient was twenty years old,female,found the right neck masses for five days,diagnosed with Hodgkin's lymphoma,mixed cell type,stage Ⅳ group B.Chose the chemotherapy regimen BV + GABVD for 4 courses,the PET-CT indicated CR,then used GABVD 4 courses,now in the stage of clinical observation and followed up.Conclusion BV is a kind of antibody-drug conjugate which targeted on CD30 protein.The FDA approved for the treatment of Hodgkin's lymphoma and systemic anaplastic large cell lymphoma.The common adverse reactions are granulocyte,peripheral neuropathy,fatigue,nausea and vomiting.BV can significantly improve the prognosis of CD30 positive Hodgkin's lymphoma,but need to pay attention to the prevention of adverse reactions.
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Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen. Owing to the remarkable efficacy shown in CD30-positive lymphomas, such as Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma, BV was granted accelerated approval in 2011 by the US Food and Drug Administration. Thereafter, many large-scale trials in various situations have been performed, which led to extensions of the original indication. The aim of this review was to describe the latest updates on clinical trials of BV and the in-practice guidance for the use of BV.
Subject(s)
Ki-1 Antigen , Financing, Organized , Hodgkin Disease , Lymphoma , Lymphoma, Large-Cell, Anaplastic , United States Food and Drug AdministrationABSTRACT
Three histological subtypes of lymphomatoid papulosis (LyP), type A (histiocytic), type B (mycosis fungoides like) and type C (anaplastic large cell lymphoma like) are well recognized. Two new histological variants, type D (simulating an aggressive epidermotropic cytotoxic lymphoma) and type E (angioinvasive type) has been described recently. We describe a 27‑year‑old man presented with a history of asymptomatic erythematous papules on both upper and lower limbs noted since 10 years of age. There were no systemic symptoms. Biopsy revealed an atypical dermal lymphoid infiltrate with epidermotropism, and the immunohistochemical markers showed a diffuse positivity for CD3, CD8, CD56, T1A and granzyme B with the focal positivity of CD30. All other relevant tests were normal. In this case report of a recently described delineated variant of LyP we emphasize the indolent course of this entity although the histology would suggest a more aggressive disease.
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CD30+ lymphoproliferative disorders (LPD) represent a spectrum of T-cell lymphoma including lymphomatoid papulosis and anaplastic large cell lymphoma (ALCL). Epidermis overlying cutaneous CD30+ LPD often shows epidermal hyperplasia, hyperkeratosis, crusting, and ulceration and it is difficult to distinguish from carcinoma such as keratoacanthoma (KA) or squamous cell carcinoma (SCC). Several cases of pseudocarcinomatous hyperplasia mimicking KA or SCC in CD30+ LPD have been reported. The relationship between CD30+ LPD and epithelial proliferations has not yet well understood. It was reported that a variety of mediators, including epidermal growth factor (EGF), transforming growth factor-α and EGFR from CD30+ LPD could attribute to epidermal hyperplasia. However, separate and distinct SCC occurring in CD30+ LPD has rarely been reported. Herein, we present a rare case of coexistence of SCC and cutaneous ALCL located on the same region.
Subject(s)
Carcinoma, Squamous Cell , Epidermal Growth Factor , Epidermis , Epithelial Cells , Hyperplasia , Keratoacanthoma , Lymphoma , Lymphoma, Large-Cell, Anaplastic , Lymphoma, Primary Cutaneous Anaplastic Large Cell , Lymphoma, T-Cell , Lymphomatoid Papulosis , Lymphoproliferative Disorders , UlcerABSTRACT
Objective To assess the feasibility of serum soluble CD30 (sCD30) as a biomarker for radiation exposure. Methods Three hundred male C57BL/6 mice were prepared and randomly divided into 4 radiation groups (60 each) and control (n=60). Mice in radiation groups were treated with 60Co total-body irradiation in the dose of 1, 3, 5 or 7 Gy, and the dose rate of 60Co ray at one-time whole-body irradiation was 0.78 Gy/min. 24, 48, or 72h after radiation, the serum samples were obtained (20 mice in each group at each time point). The serum sCD30 concentrations were analyzed with custom-made antibody array, which was purchased from RayBiotech. To further analyze the relationships of serum sCD30 concentration and radiation dose, regression analysis was used. Results The baseline level of sCD30 in serum of non-exposed animals was 121.2±25.61pg/ml. Moreover, serum sCD30 concentration was inversely related to the radiation dose during 72h after exposure. Regression analysis showed an obvious dose-effect relationship between serum sCD30 concentration and radiation dose (24h after radiation, R2=0.8715; 48h after radiation, R2=0.9024; 72h after radiation, R2=0.9913). Using these equations, radiation exposure can be easily estimated by the serum sCD30 value. Conclusions The baseline level of serum sCD30 remains steady without radiation. Further regression analysis uncovers a strong correlation between serum sCD30 concentration and radiation dose, and serum sCD30 may be used to estimate radiation exposure as a biomarker.
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OBJECTIVE: To develop a heterogeneity analysis method of an antibody-drug conjugate (anti-CD30-vc-MMAE). METHODS: The size and charge heterogeneity of the antibody-drug conjugate (anti CD30-vc-MMAE) was analyzed by SEC-HPLC, CE-SDS, and iCIEF. RESULTS: The main peak purity was (95.69±0.01)% as shown by SEC-HPLC. The total peak purity of the heavy and light chains determined by reduced CE-SDS was (98.38±0.25%)%. At non-reduced CE-SDS level, there were six main peaks, and the total purity of which was (97.82±0.44)%. The acid modification, base modification, and main proportion could be separated effectively by iCIEF, and the peak area percentage of the main peak was (43.52±2.03)%. CONCLUSION: A heterogenecity analysis method of the antibody-drug conjugate (anti-CD30-vc-MMAE) has been preliminarily established and can provide reference for the quality control of this product.