传统抗体偶联药物(antibody drug conjugates,ADC)通过将单克隆抗体与细胞毒性药物相结合,实现对癌细胞的精准打击,但在稳定性、靶向性、疗效及安全性等方面依然存在诸多不足。新型ADC,如双特异性、位点特异性、双有效载荷和前药型ADC,...传统抗体偶联药物(antibody drug conjugates,ADC)通过将单克隆抗体与细胞毒性药物相结合,实现对癌细胞的精准打击,但在稳定性、靶向性、疗效及安全性等方面依然存在诸多不足。新型ADC,如双特异性、位点特异性、双有效载荷和前药型ADC,通过同时结合2个不同抗原或表位、选择更稳定的连接子、与抗体特定氨基酸位点偶联、携带不同药物有效载荷以及采用前药策略等优化方法,在保留传统ADC作用特点的基础上,显著提高药物的稳定性、靶向性、疗效和安全性,能更好地满足临床治疗的需求。新型ADC可能会在未来的癌症治疗中发挥重要的作用。探讨新型ADC在癌症治疗中的进展并分析其优势与挑战,可为开发抗癌策略提供理论支持,为药物研发提供方向。展开更多
In a previous report we had reported on the discovery of a novel bispecific immunoglobulin expressed by colonic epithelial cells as they transform into immunomimetic cells during exfoliation (Albaugh <i>et al. &...In a previous report we had reported on the discovery of a novel bispecific immunoglobulin expressed by colonic epithelial cells as they transform into immunomimetic cells during exfoliation (Albaugh <i>et al. </i> (2020) <i>Open Journal of Preventive Medicine</i>, 10, 126-150). Colonic cells isolated from 0.5 gm aliquots of fresh stools (SCSR-10, Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD) preserved at room temperature for up to one week, with viability of >85% were used to determine the number of cells expressing this novel bispecific immunoglobulin. Over the course of this period (18 years) we recognized that these cells opened the opportunity to investigate the expression of cell membrane biomarkers. As the applications grew, we introduced a new terminology, termed COPROCYTOBIOLOGY*. In this study, we surveyed a cohort of 58 free-living adults for the expression of the newly discovered bi-specific chimeric antibody. Almost all of the subjects showed a strong signal during flow-cytometric evaluation of their stool samples;averaging around 65%. However, two subjects exhibited a total loss of this signal and both these individuals were of African-American lineage (one male and one female). These cells upon culturing <i>in vitro</i> remained defective in contrast to the rest of the group where their progeny continued to generate the antibody. We propose that this signals the existence of a germ-line deletion of the gene for which a novel test (MEDISHIELD†) is suggested. This syndrome may be associated with a lack of response to prophylactic vaccines involving m-RNA.展开更多
To evaluate the effect of anti-HER-2 × anti-CD3 bi-specific antibody（BsAb） on the growth of HER-2/neu-expressing human gastric carcinoma in vitro and in vivo, an MTT assay was carried out to test the inhibitive...To evaluate the effect of anti-HER-2 × anti-CD3 bi-specific antibody（BsAb） on the growth of HER-2/neu-expressing human gastric carcinoma in vitro and in vivo, an MTT assay was carried out to test the inhibitive rates of herceptin, anti-CD3 and BsAb antibodies on SGC-7901 gastric carcinoma cells. Immunocytochemistry methods were used to test the HER-2 level of SGC-7901. Nude mice models were employed to test the effect of HER-2 CD3 BsAh combined with effector ceils（ peripheral blood lymphatic cells of healthy human beings） on the growth of tumors in animals. Compared with that of the untreated control group, the tumor cell growth rates in vitro and in vivo will both be significantly inhibited when treated with effector cells combined with anti-CD3 McAb, herceptin or HER2 CD3 BsAb （p 〈0. 05）, and the growth inhibition is the most remarkable in the group treated with HER2 CD3 BsAb combined with effector cells. The growth of tumor xenografts will also be significantly inhibited in the group treated with HER2 CD3 BsAb combined with effector cells when compared with that in the group treated with anti-CD3 McAb or the group treated with herceptin combined with effector cells（p 〈0. 05）. We can conclude that HER-2/neu is possibly a useful target for immunotherapy of gastric carcinoma, and anti-HER2 × anti-CD3 BsAb has evident anti-tumor efficacy both, in vitro and in vivo.展开更多
目的将新近建立的单管双向等位基因专一性扩增(single-tube bi-directional allele specific amplification,SB-ASA)方法用于分析近交系小鼠基因组中的单核苷酸多态性(SNP)。方法以5个近交系小鼠为研究对象,采用SB-ASA方法对其16个SNP...目的将新近建立的单管双向等位基因专一性扩增(single-tube bi-directional allele specific amplification,SB-ASA)方法用于分析近交系小鼠基因组中的单核苷酸多态性(SNP)。方法以5个近交系小鼠为研究对象,采用SB-ASA方法对其16个SNP位点进行检测,并通过双盲实验和测序验证该方法的可靠性;且考察了该方法中PCR反应各成分及扩增条件对结果的影响。结果16个SNP位点,SB-ASA都成功地对5个品系小鼠进行了分型,与测序结果完全一致;双盲实验结果显示通过3个SNP位点即可鉴别5个品系。结论SB-ASA方法可用于近交系小鼠SNP的遗传检测,可望作为一种新的分子生物学遗传检测方法推广应用。展开更多
目的建立leptinob和leptinrdb等位基因的SNP分型方法-单管双向等位基因专一性扩增(single-tubebi-directional allele specific amplification,SB-ASA),同时与传统的PCR-酶切法进行比较分析。方法用PCR-酶切法和SB-ASA方法同时对ob/+杂...目的建立leptinob和leptinrdb等位基因的SNP分型方法-单管双向等位基因专一性扩增(single-tubebi-directional allele specific amplification,SB-ASA),同时与传统的PCR-酶切法进行比较分析。方法用PCR-酶切法和SB-ASA方法同时对ob/+杂合小鼠的7只后代小鼠和db/m的9只后代小鼠进行了检测分型。结果两种方法都成功地对ob、db小鼠进行了分型,且结果完全一致。结论成功建立了一种快速的leptinob和leptinrdb等位基因的SNP分型方法-SB-ASA,促进了ob、db小鼠的繁殖育种工作。展开更多
文摘传统抗体偶联药物(antibody drug conjugates,ADC)通过将单克隆抗体与细胞毒性药物相结合,实现对癌细胞的精准打击,但在稳定性、靶向性、疗效及安全性等方面依然存在诸多不足。新型ADC,如双特异性、位点特异性、双有效载荷和前药型ADC,通过同时结合2个不同抗原或表位、选择更稳定的连接子、与抗体特定氨基酸位点偶联、携带不同药物有效载荷以及采用前药策略等优化方法,在保留传统ADC作用特点的基础上,显著提高药物的稳定性、靶向性、疗效和安全性,能更好地满足临床治疗的需求。新型ADC可能会在未来的癌症治疗中发挥重要的作用。探讨新型ADC在癌症治疗中的进展并分析其优势与挑战,可为开发抗癌策略提供理论支持,为药物研发提供方向。
文摘In a previous report we had reported on the discovery of a novel bispecific immunoglobulin expressed by colonic epithelial cells as they transform into immunomimetic cells during exfoliation (Albaugh <i>et al. </i> (2020) <i>Open Journal of Preventive Medicine</i>, 10, 126-150). Colonic cells isolated from 0.5 gm aliquots of fresh stools (SCSR-10, Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD) preserved at room temperature for up to one week, with viability of >85% were used to determine the number of cells expressing this novel bispecific immunoglobulin. Over the course of this period (18 years) we recognized that these cells opened the opportunity to investigate the expression of cell membrane biomarkers. As the applications grew, we introduced a new terminology, termed COPROCYTOBIOLOGY*. In this study, we surveyed a cohort of 58 free-living adults for the expression of the newly discovered bi-specific chimeric antibody. Almost all of the subjects showed a strong signal during flow-cytometric evaluation of their stool samples;averaging around 65%. However, two subjects exhibited a total loss of this signal and both these individuals were of African-American lineage (one male and one female). These cells upon culturing <i>in vitro</i> remained defective in contrast to the rest of the group where their progeny continued to generate the antibody. We propose that this signals the existence of a germ-line deletion of the gene for which a novel test (MEDISHIELD†) is suggested. This syndrome may be associated with a lack of response to prophylactic vaccines involving m-RNA.
文摘To evaluate the effect of anti-HER-2 × anti-CD3 bi-specific antibody（BsAb） on the growth of HER-2/neu-expressing human gastric carcinoma in vitro and in vivo, an MTT assay was carried out to test the inhibitive rates of herceptin, anti-CD3 and BsAb antibodies on SGC-7901 gastric carcinoma cells. Immunocytochemistry methods were used to test the HER-2 level of SGC-7901. Nude mice models were employed to test the effect of HER-2 CD3 BsAh combined with effector ceils（ peripheral blood lymphatic cells of healthy human beings） on the growth of tumors in animals. Compared with that of the untreated control group, the tumor cell growth rates in vitro and in vivo will both be significantly inhibited when treated with effector cells combined with anti-CD3 McAb, herceptin or HER2 CD3 BsAb （p 〈0. 05）, and the growth inhibition is the most remarkable in the group treated with HER2 CD3 BsAb combined with effector cells. The growth of tumor xenografts will also be significantly inhibited in the group treated with HER2 CD3 BsAb combined with effector cells when compared with that in the group treated with anti-CD3 McAb or the group treated with herceptin combined with effector cells（p 〈0. 05）. We can conclude that HER-2/neu is possibly a useful target for immunotherapy of gastric carcinoma, and anti-HER2 × anti-CD3 BsAb has evident anti-tumor efficacy both, in vitro and in vivo.
文摘目的将新近建立的单管双向等位基因专一性扩增(single-tube bi-directional allele specific amplification,SB-ASA)方法用于分析近交系小鼠基因组中的单核苷酸多态性(SNP)。方法以5个近交系小鼠为研究对象,采用SB-ASA方法对其16个SNP位点进行检测,并通过双盲实验和测序验证该方法的可靠性;且考察了该方法中PCR反应各成分及扩增条件对结果的影响。结果16个SNP位点,SB-ASA都成功地对5个品系小鼠进行了分型,与测序结果完全一致;双盲实验结果显示通过3个SNP位点即可鉴别5个品系。结论SB-ASA方法可用于近交系小鼠SNP的遗传检测,可望作为一种新的分子生物学遗传检测方法推广应用。
文摘目的建立leptinob和leptinrdb等位基因的SNP分型方法-单管双向等位基因专一性扩增(single-tubebi-directional allele specific amplification,SB-ASA),同时与传统的PCR-酶切法进行比较分析。方法用PCR-酶切法和SB-ASA方法同时对ob/+杂合小鼠的7只后代小鼠和db/m的9只后代小鼠进行了检测分型。结果两种方法都成功地对ob、db小鼠进行了分型,且结果完全一致。结论成功建立了一种快速的leptinob和leptinrdb等位基因的SNP分型方法-SB-ASA,促进了ob、db小鼠的繁殖育种工作。
