嵌合抗原受体(CAR)技术在血液肿瘤治疗中的研究进展

嵌合抗原受体是一种基础性的免疫治疗,经过近二十五年的发展,它已经成了治疗恶性肿瘤的新希望。随着对新的特异性肿瘤标志物的不断发现以及基因工程技术的不断发展,嵌合抗原受体技术越来越成熟,即将在临床上得到广泛应用。嵌合抗原受体技术治疗方法在血液肿瘤的治疗中存在显著的优势,取得了新的突破。本文主要对嵌合抗原受体技术在血液肿瘤免疫治疗中的应用进行回顾性分析,对其优势、创新、应用现状以及未来发展进行了深入分析。

基因修饰树突状细胞诱导抗血液肿瘤效应的研究进展

白血病/淋巴瘤等血液肿瘤经联合化疗,可以获得完全缓解,但难彻底消灭肿瘤微小残留病(MRD)。基因修饰的树突状细胞瘤苗以其增强肿瘤细胞的免疫原性,启动机体的特异性抗肿瘤免疫应答,成为清除MRD的一种有希望的途径。本文就树突状细胞的生物学特性及其诱导培养,基因转移载体的选择,以及不同来源基因修饰DC诱导抗血液肿瘤的特点等方面的研究进展进行综述。

The immunophenotypic changes and clinical effectiveness after treatment of cancer patients with infusion of human peripheral blood lymphocytes stimulated by anti-CD28 and anti-CD80 monoclonal antibodies in combination with radiotherapy and chemotherapy

To investigate the changes on the immunopbenotypes and the clinical effects of treatment of the late cancer patients with infusion of human peripheral blood lymphocytes stimulated by anti-CD28 and anti-CD80 monoclonal antibodies in combination with radiotherapy and chemotherapy, 42 patients with late cancers were collected for study, among which 22 patients were treated with infusion of stimulated lymphocytes in combination with radiotherapy and chemotherapy. The immunological treatment procedure was given twice per week, and one course of treatment consisted of 8 times of giving infusion of lymphocytes. Another 20 patients were selected for control group, in which only radiotherapy and chemotherapy were given without lymphocyte infusions. Flow cytometry was used to examine the immunophenotypes and the clinical symptoms were observed before and after treatments. It was found that the numbers of the CD3^ ＋ , CD4^＋ cells increased, while those of the CD8 ^＋ cells decreased, with an increase of CD4/CD8 radios, but no significant difference existed in case of 22 patients treated with lymphocyte infusion as well as with radiotherapy and chemotherapy. Fifteen patients out of these 22 cases （68.18%）, the immunophenotypes changed obviously with increased numbers of CD3^ ＋ , CD4^ ＋ cells in comparison with those before treatment, and the number of CD95^ ＋ cells was increased after treatment. The PS value in this group of patients decreased after treatment. In comparison with 20 cases in the control group, the immunophenotypes showed no differences before and after treatment. While the PS value decreased obviously. Seven out of the 22 cases （31.83 % ） treated with lymphocyte infusions as well as with radiotherapy and chemotherapy illustrated no major changes in their i mmunophenotypes, compared with the situation before treatment, but the PS value also decreased. In case of treatment with lymphocyte infusions in combination with radiotherapy and chemotherapy, the alteration of phenotypes was reversely correlated with the changes of clinical grades. Although there were 7 cases showing no major alterations of the immunological phenotypes, but their correlation was still evident. In the control group, neither alteration of immunophenotypes nor changes in clinical grades was found. It is concluded that immunotherapy in combination with radiotherapy and chemotherapy can relieve the side effects induced by radiotherapy and chemotherapy and also enhance the therapeutic efforts.

Weathering the storm:COVID-19 infection in patients with hematological malignancies

The coronavirus disease 2019(COVID-19)is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Within a matter of months,this highly contagious novel virus has led to a global outbreak and is still spreading rapidly across continents.In patients with COVID-19,underlying chronic diseases and comorbidities are associated with dismal treatment outcomes.Owing to their immunosuppressive status,patients with hematological malignancies(HMs)are at an increased risk of infection and have a worse prognosis than patients without HMs.Accordingly,intensive attention should be paid to this cohort.In this review,we summarize and analyze specific clinical manifestations for patients with coexisting COVID-19 and HMs.Furthermore,we briefly de-scribe customized management strategies and interventions for this susceptible cohort.This review is intended to guide clinical practice.

Enhance anti-lung tumor efficacy of chimeric antigen receptor-T cells by ectopic expression of C-C motif chemokine receptor 6

Chimeric antigen receptor-T(CAR-T)cells have limited therapeutic efficacy against solid tumors,partially due to their limited ability to reach and invade into the neoplastic foci.By gene expression profiling interactive analysis,we identified that the C-C motif chemokine ligand(CCL)20 is highly expressed in lung and other most incidence and/or mortality cancers such as colon,rectum,stomach,and liver cancers.Forced expression of C-C motif chemokine receptor 6(CCR6),the biunique receptor of CCL20,results in robust trafficking of CAR-T cells toward CCL20-secreting tumor cells.In a lung cancer xenograft mouse model,CCR6-expressing CAR-T cells efficiently migrate to and infiltrate into solid tumors upon infusion,leading to effective tumor clearance and significantly prolonged survival of tumor-bearing mice.In addition,culturing CCR6-CAR-T cells with interleukin(IL)-7 and IL-15 further improved their anti-lung cancer activity.Our findings provide supporting evidence for the clinical development of chemokine receptorengineered CAR-T cells for solid tumor immunotherapy.