公开(公告)号：US11052140B2

公开(公告)日：2021-07-06

申请号：US16450302

申请日：2019-06-24

申请人： Cassian Yee ,  Yongqing Li ,  C. Siddiq Abdul-Alim

发明人： Cassian Yee ,  Yongqing Li ,  C. Siddiq Abdul-Alim

IPC分类号： A61K39/00 ,  C07K14/47

摘要： What is described is a method of treatment of a patient with a tumor, comprising administering a cell responsive to a peptide comprising a tumor epitope, wherein the tumor epitope comprises an amino acid substitution in a tumor antigen. The tumor antigen is preferably selected from the group consisting of NYESO-I157-165, NYESO-II157-170, or MART-126-35, preferably SEQ ID NOS: 1-351, 361-376, and 392-401.

公开(公告)号：US09809797B2

公开(公告)日：2017-11-07

申请号：US12677035

申请日：2008-09-25

申请人： Cassian Yee ,  Yongqing Li

发明人： Cassian Yee ,  Yongqing Li

IPC分类号： C12N5/0783 ,  A61K31/41 ,  A61K39/00 ,  A61K35/17 ,  A61K35/12

CPC分类号： C12N5/0638 ,  A61K31/41 ,  A61K35/12 ,  A61K35/17 ,  A61K39/00 ,  A61K2035/124 ,  A61K2039/51 ,  A61K2039/5154 ,  C12N5/0636 ,  C12N2501/23 ,  C12N2501/2321 ,  C12N2501/998

摘要： A method of carrying out adoptive immunotherapy by administering a subject an antigen-specific cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount is described. In the method, the CTL preparation is preferably administered as a preparation of an in vitro antigen-stimulated and expanded primate CTL population, the CTL population: (i) depleted of FoxP3+ T lymphocytes prior to antigen stimulation; (ii) antigen-stimulated in vitro in the presence of interleukin-21; or (iii) both depleted of FoxP3+ T lymphocytes prior to antigen stimulation and then antigen-stimulated in vitro in the presence of interleukin-21. Methods of preparing such compositions, and compositions useful for carrying out the adoptive immunotherapy, are also described.

公开(公告)号：US20100330056A1

公开(公告)日：2010-12-30

申请号：US12677035

申请日：2008-09-25

申请人： Cassian Yee ,  Yongqing Li

发明人： Cassian Yee ,  Yongqing Li

IPC分类号： A61K35/12 ,  C12N5/0783 ,  A61P35/00 ,  A61P31/00 ,  A61P37/00

CPC分类号： C12N5/0638 ,  A61K31/41 ,  A61K35/12 ,  A61K35/17 ,  A61K39/00 ,  A61K2035/124 ,  A61K2039/51 ,  A61K2039/5154 ,  C12N5/0636 ,  C12N2501/23 ,  C12N2501/2321 ,  C12N2501/998

摘要： A method of carrying out adoptive immunotherapy by administering a subject an antigen-specific cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount is described. In the method, the CTL preparation is preferably administered as a preparation of an in vitro antigen-stimulated and expanded primate CTL population, the CTL population: (i) depleted of FoxP3+ T lymphocytes prior to antigen stimulation; (ii) antigen-stimulated in vitro in the presence of interleukin-21; or (iii) both depleted of FoxP3+ T lymphocytes prior to antigen stimulation and then antigen-stimulated in vitro in the presence of interleukin-21. Methods of preparing such compositions, and compositions useful for carrying out the adoptive immunotherapy, are also described.

摘要翻译： 描述了以治疗有效量给予受试者抗原特异性细胞毒性T淋巴细胞（CTL）制剂进行过继性免疫治疗的方法。 在该方法中，CTL制剂优选作为体外抗原刺激和扩增的灵长类动物CTL群体的制剂施用，CTL群体：（i）在抗原刺激之前耗尽FoxP3 + T淋巴细胞; （ii）在白介素-21的存在下体外抗原刺激; 或（iii）在抗原刺激之前都耗尽FoxP3 + T淋巴细胞，然后在白细胞介素-II存在下体外抗原刺激。 还描述了制备这种组合物的方法和用于进行过继性免疫治疗的组合物。

公开(公告)号：US20130108657A1

公开(公告)日：2013-05-02

申请号：US13696303

申请日：2011-11-10

申请人： Cassian Yee ,  Yongqing Li ,  C. Siddiq Abdul-Alim

发明人： Cassian Yee ,  Yongqing Li ,  C. Siddiq Abdul-Alim

IPC分类号： A61K39/00

CPC分类号： A61K39/0011 ,  A61K2039/515 ,  A61K2039/57 ,  A61K2039/572 ,  C07K14/4748

摘要： What is described is a novel genetic screen, involving recombinant technology and class I antigen cross-presentation, to search for supraoptimal superagonists of the 27L MART-1 mutant selecting for single amino acid substitution mutants of 27L that activate human antigen-specific CTL clones recognizing the wild-type MART-126-35 epitope. Three novel mutant epitopes are identified with superagonist properties that are functionally superior to 27L. The ability of a given analog to act as superagonist varies among patients. Also described is the use of methods to establish panels of potential superagonist APLs to individualize tumor peptide vaccines among patients. The methodology is replicated to identify APL to NY-ESO-1157-165 and NY-ESO-1157-170 tumor epitopes. A general method is described that is useful to produce a tumor vaccine to any tumor epitope.

摘要翻译： 描述的是一种新型遗传筛选，涉及重组技术和I类抗原交叉呈递，以搜索27L MART-1突变体的超最佳超抗体，其选择27L的单个氨基酸取代突变体，其激活识别的人抗原特异性CTL克隆 野生型MART-126-35表位。 三个新的突变体表位被鉴定为具有功能优于27L的超强度属性。 给予类似物作为超级运动员的能力因患者而异。 还描述了使用方法来建立潜在的超级拮抗剂APL的小组，以在患者之间个体化肿瘤肽疫苗。 该方法被复制以鉴定到NY-ESO-1157-165和NY-ESO-1157-170肿瘤表位的APL。 描述了可用于产生任何肿瘤表位的肿瘤疫苗的一般方法。

公开(公告)号：US20200000898A1

公开(公告)日：2020-01-02

申请号：US16450302

申请日：2019-06-24

申请人： Cassian Yee ,  Yongqing Li ,  C. Siddiq Abdul-Alim

发明人： Cassian Yee ,  Yongqing Li ,  C. Siddiq Abdul-Alim

IPC分类号： A61K39/00 ,  C07K14/47

摘要： What is described is a method of treatment of a patient with a tumor, comprising administering a cell responsive to a peptide comprising a tumor epitope, wherein the tumor epitope comprises an amino acid substitution in a tumor antigen. The tumor antigen is preferably selected from the group consisting of NYESO-I157-165, NYESO-II157-170, or MART-126-35, preferably SEQ ID NOS: 1-351, 361-376, and 392-401.

公开(公告)号：US10328135B2

公开(公告)日：2019-06-25

申请号：US15098274

申请日：2016-04-13

申请人： Cassian Yee ,  Yongqing Li ,  C. Siddiq Abdul-Alim

发明人： Cassian Yee ,  Yongqing Li ,  C. Siddiq Abdul-Alim

IPC分类号： A61K39/00 ,  C07K14/47

摘要： What is described is a novel genetic screen, involving recombinant technology and class I antigen cross-presentation, to search for supraoptimal superagonists of the 27L MART-1 mutant selecting for single amino acid substitution mutants of 27L that activate human antigen-specific CTL clones recognizing the wild-type MART-126-35 epitope. Three novel mutant epitopes are identified with superagonist properties that are functionally superior to 27L. The ability of a given analog to act as superagonist varies among patients. Also described is the use of methods to establish panels of potential superagonist APLs to individualize tumor peptide vaccines among patients. The methodology is replicated to identify APL to NYESO-1157-165 and NYESO-1157-170 tumor epitopes. A general method is described that is useful to produce a tumor vaccine to any tumor epitope.

公开(公告)号：US20160317633A1

公开(公告)日：2016-11-03

申请号：US15098274

申请日：2016-04-13

申请人： Cassian Yee ,  Yongqing Li ,  C. Siddiq Abdul-Alim

发明人： Cassian Yee ,  Yongqing Li ,  C. Siddiq Abdul-Alim

IPC分类号： A61K39/00

CPC分类号： A61K39/0011 ,  A61K2039/515 ,  A61K2039/57 ,  A61K2039/572 ,  C07K14/4748

摘要： What is described is a novel genetic screen, involving recombinant technology and class I antigen cross-presentation, to search for supraoptimal superagonists of the 27L MART-1 mutant selecting for single amino acid substitution mutants of 27L that activate human antigen-specific CTL clones recognizing the wild-type MART-1.sub.26-35 epitope. Three novel mutant epitopes are identified with superagonist properties that are functionally superior to 27L. The ability of a given analog to act as superagonist varies among patients. Also described is the use of methods to establish panels of potential superagonist APLs to individualize tumor peptide vaccines among patients. The methodology is replicated to identify APL to NY-ESO-1.sub.157-165 and NY-ESO-1.sub.157-170 tumor epitopes. A general method is described that is useful to produce a tumor vaccine to any tumor epitope.

摘要翻译： 描述的是一种新型遗传筛选，涉及重组技术和I类抗原交叉呈递，以搜索27L MART-1突变体的超最佳超抗体，其选择27L的单个氨基酸取代突变体，其激活识别的人抗原特异性CTL克隆 野生型MART-1.sub.26-35表位。 三个新的突变体表位被鉴定为具有功能优于27L的超强度属性。 给予类似物作为超级运动员的能力因患者而异。 还描述了使用方法来建立潜在的超级拮抗剂APL的小组，以在患者之间个体化肿瘤肽疫苗。 该方法被复制以鉴定到NY-ESO-1.57-165和NY-ESO-1,557-170肿瘤表位的APL。 描述了可用于产生任何肿瘤表位的肿瘤疫苗的一般方法。

公开(公告)号：US09314516B2

公开(公告)日：2016-04-19

申请号：US13696303

申请日：2011-05-04

申请人： Cassian Yee ,  Yongqing Li ,  C. Siddiq Abdul-Alim

发明人： Cassian Yee ,  Yongqing Li ,  C. Siddiq Abdul-Alim

IPC分类号： A61K39/00 ,  C07K7/00 ,  C07K14/47

CPC分类号： A61K39/0011 ,  A61K2039/515 ,  A61K2039/57 ,  A61K2039/572 ,  C07K14/4748

摘要： What is described is a novel genetic screen, involving recombinant technology and class I antigen cross-presentation, to search for supraoptimal superagonists of the 27L MART-1 mutant selecting for single amino acid substitution mutants of 27L that activate human antigen-specific CTL clones recognizing the wild-type MART-126-35 epitope. Three novel mutant epitopes are identified with superagonist properties that are functionally superior to 27L. The ability of a given analog to act as superagonist varies among patients. Also described is the use of methods to establish panels of potential superagonist APLs to individualize tumor peptide vaccines among patients. The methodology is replicated to identify APL to NY-ESO-1157-165 and NY-ESO-1157-170 tumor epitopes. A general method is described that is useful to produce a tumor vaccine to any tumor epitope.

摘要翻译： 描述的是一种新型遗传筛选，涉及重组技术和I类抗原交叉呈递，以搜索27L MART-1突变体的超最佳超抗体，其选择27L的单个氨基酸取代突变体，其激活识别的人抗原特异性CTL克隆 野生型MART-126-35表位。 三个新的突变体表位被鉴定为具有功能优于27L的超强度属性。 给予类似物作为超级运动员的能力因患者而异。 还描述了使用方法来建立潜在的超级拮抗剂APL的小组，以在患者之间个体化肿瘤肽疫苗。 该方法被复制以鉴定到NY-ESO-1157-165和NY-ESO-1157-170肿瘤表位的APL。 描述了可用于产生任何肿瘤表位的肿瘤疫苗的一般方法。

公开(公告)号：US20060269973A1

公开(公告)日：2006-11-30

申请号：US11285970

申请日：2005-11-23

申请人： Cassian Yee

发明人： Cassian Yee

IPC分类号： G01N33/574 ,  C12N5/08

CPC分类号： C12N5/0638 ,  A61K35/17 ,  C12N5/0636 ,  C12N2501/23 ,  C12N2501/2321 ,  C12N2502/1121 ,  G01N33/5047 ,  G01N33/505 ,  G01N33/574 ,  G01N33/57484 ,  G01N33/57492 ,  G01N33/6863

摘要： Methods for preparing ex vivo T cell cultures using IL-21 compositions for use in adoptive immunotherapy are described. Addition of IL-21 to cultures of non-terminally differentiated T cells population, either isolated or present in peripheral blood mononuclear cells are exposed to one or more tumor antigens, and in the presence of IL-21 compositions and antigen presenting cells (APCs), the resulting T cell population has an enhanced antigen-specificity, and can be reintroduced into the patient. Methods are also disclosed for identifying tumor antigens by culturing T cell populations exposed to IL-21 compositions and APCs in the presence of tumor material.

摘要翻译： 描述了使用IL-21组合物制备用于过继性免疫治疗的离体T细胞培养物的方法。 在外周血单核细胞中分离或存在的非终末分化的T细胞群的培养物中加入IL-21暴露于一种或多种肿瘤抗原，并且在存在IL-21组合物和抗原呈递细胞（APC）的情况下， ，所得的T细胞群体具有增强的抗原特异性，并且可以重新引入患者体内。 还公开了通过在肿瘤材料存在下培养暴露于IL-21组合物和APC的T细胞群来鉴定肿瘤抗原的方法。

公开(公告)号：US20100310533A1

公开(公告)日：2010-12-09

申请号：US12617018

申请日：2009-11-12

申请人： Cassian Yee

发明人： Cassian Yee

IPC分类号： A61K35/12 ,  C12Q1/02 ,  C12Q1/68 ,  C12N5/0783 ,  A61P37/00

CPC分类号： C12N5/0638 ,  A61K35/17 ,  C12N5/0636 ,  C12N2501/23 ,  C12N2501/2321 ,  C12N2502/1121 ,  G01N33/5047 ,  G01N33/505 ,  G01N33/574 ,  G01N33/57484 ,  G01N33/57492 ,  G01N33/6863

摘要： Methods for preparing ex vivo T cell cultures using IL-21 compositions for use in adoptive immunotherapy are described. Addition of IL-21 to cultures of non-terminally differentiated T cells population, either isolated or present in peripheral blood mononuclear cells are exposed to one or more tumor antigens, and in the presence of IL-21 compositions and antigen presenting cells (APCs), the resulting T cell population has an enhanced antigen-specificity, and can be reintroduced into the patient. Methods are also disclosed for identifying tumor antigens by culturing T cell populations exposed to IL-21 compositions and APCs in the presence of tumor material.

摘要翻译： 描述了使用IL-21组合物制备用于过继性免疫治疗的离体T细胞培养物的方法。 在外周血单核细胞中分离或存在的非终末分化的T细胞群的培养物中加入IL-21暴露于一种或多种肿瘤抗原，并且在存在IL-21组合物和抗原呈递细胞（APC）的情况下， ，所得的T细胞群体具有增强的抗原特异性，并且可以重新引入患者体内。 还公开了通过在肿瘤材料存在下培养暴露于IL-21组合物和APC的T细胞群来鉴定肿瘤抗原的方法。